Range.......1

Through the late 1920s and early 1930s, remote reaches of the Soviet Union were forced through social and economic changes that would normally take generations. Individual farmers in isolated areas of what is now Uzbekistan had long survived by cultivating small gardens for food, and cotton for everything else. Nearby in the mountain pasturelands of present-day Kyrgyzstan, herders kept animals. The population was entirely illiterate, and a hierarchical social structure was enforced by strict religious rules. The socialist revolution dismantled that way of life almost overnight. The Soviet government forced all that agricultural land to become large collective farms and began industrial development. The economy quickly became interconnected and complex. Farmers had to form collective work strategies, plan ahead for production, divvy up functions, and assess work along the way. Remote villages began communicating with distant cities. A network of schools opened in regions with 100 percent illiteracy, and adults began learning a system of matching symbols to sounds. Villagers had used numbers before, but only in practical transactions. Now they were taught the concept of a number as an abstraction that existed even without reference to counting animals or apportioning food. Some village women remained fully illiterate but took short courses on how to teach kindergartners. Other women were admitted for longer study at a teachers’ school. Classes in preschool education and the science and technology of agriculture were offered to students who had no formal education of any kind. Secondary schools and technical institutes soon followed. In 1931, amid that incredible transformation, a brilliant young Russian psychologist named Alexander Luria recognized a fleeting “natural experiment,” unique in the history of the world. He wondered if changing citizens’ work might also change their minds

When Luria arrived, the most remote villages had not yet been touched by the warp-speed restructuring of traditional society. Those villages gave him a control group. He learned the local language and brought fellow psychologists to engage villagers in relaxed social situations—teahouses or pastures—and discuss questions or tasks designed to discern their habits of mind. Some were very simple: present skeins of wool or silk in an array of hues and ask participants to describe them. The collective farmers and farm leaders, as well as the female students, easily picked out blue, red, and yellow, sometimes with variations, like dark blue or light yellow. The most remote villagers, who were still “premodern,” gave more diversified descriptions: cotton in bloom, decayed teeth, a lot of water, sky, pistachio. Then they were asked to sort the skeins into groups. The collective farmers, and young people with even a little formal education, did so easily, naturally forming color groups. Even when they did not know the name of a particular color, they had little trouble putting together darker and lighter shades of the same one. The remote villagers, on the other hand, refused, even those whose work was embroidery. “It can’t be done,” they said, or, “None of them are the same, you can’t put them together.” When prodded vigorously, and only if they were allowed to make many small groups, some relented and created sets that were apparently random. A few others appeared to sort the skeins according to color saturation, without regard to the color. Geometric shapes followed suit. The greater the dose of modernity, the more likely an individual grasped the abstract concept of “shapes” and made groups of triangles, rectangles, and circles, even if they had no formal education and did not know the shapes’ names.

The remote villagers, meanwhile, saw nothing alike in a square drawn with solid lines and the same exact square drawn with dotted lines. To Alieva, a twenty-six-year-old remote villager, the solid-line square was obviously a map, and the dotted-line square was a watch. “How can a map and a watch be put together?” she asked, incredulous. Khamid, a twenty-four-year-old remote villager, insisted that filled and unfilled circles could not go together because one was a coin and the other a moon. The pattern continued for every genre of question. Pressed to make conceptual groupings—akin to the similarities questions on IQ tests—remote villagers reverted to practical narratives based on their direct experience. When psychologists attempted to explain a “which one does not belong” grouping exercise to thirty-nine-year-old Rakmat, they gave him the example of three adults and one child, with the child obviously different from the others. Except Rakmat could not see it that way. “The boy must stay with the others!” he argued. The adults are working, “and if they have to keep running out to fetch things, they’ll never get the job done, but the boy can do the running for them.” Okay, then, how about a hammer, a saw, a hatchet, and a log—three of them are tools. They are not a group, Rakmat replied, because they are useless without the log, so why would they be together?

Other villagers removed either the hammer or the hatchet, which they saw as less versatile for use with the log, unless they considered pounding the hatchet into the log with the hammer, in which case it could stay. Perhaps, then, bird/ rifle/ dagger/ bullet? You can’t possibly remove one and have a group, a remote villager insisted. The bullet must be loaded in the rifle to kill the bird, and “then you have to cut the bird up with the dagger, since there’s no other way to do it.” These were just the introductions explaining the grouping task, not the actual questions. No amount of cajoling, explanation, or examples could get remote villagers to use reasoning based on any concept that was not a concrete part of their daily lives. The farmers and students who had begun to join the modern world were able to practice a kind of thinking called “eduction,” to work out guiding principles when given facts or materials, even in the absence of instructions, and even when they had never seen the material before. This, it turns out, is precisely what Raven’s Progressive Matrices tests. Imagine presenting the villagers living in premodern circumstances with abstract designs from the Raven’s test. Some of the changes wrought by modernity and collective culture seem almost magical. Luria found that most remote villagers were not subject to the same optical illusions as citizens of the industrialized world, like the Ebbinghaus illusion. Which middle circle below looks bigger?

If you said the one on the right, you’re probably a citizen of the industrialized world. The remote villagers saw, correctly, that they are the same, while the collective farmers and women in teachers’ school picked the one on the right. Those findings have been repeated in other traditional societies, and scientists have suggested it may reflect the fact that premodern people are not as drawn to the holistic context—the relationship of the various circles to one another—so their perception is not changed by the presence of extra circles. To use a common metaphor, premodern people miss the forest for the trees; modern people miss the trees for the forest. Since Luria’s voyage to the interior, scientists have replicated his work in other cultures. The Kpelle people in Liberia were subsistence rice farmers, but in the 1970s roads began snaking toward them, connecting the Kpelle to cities. Given similarities tests, teenagers who were engaged with modern institutions grouped items by abstract categories (“All of these things can keep us warm”), while the traditional teens generated groups that were comparatively arbitrary, and changed frequently even when they were asked to repeat the exact same task. Because the touched-by-modernity teens had constructed meaningful thematic groups, they also had far superior recall when asked later to recount the items. The more they had moved toward modernity, the more powerful their abstract thinking, and the less they had to rely on their concrete experience of the world as a reference point.

Time Inversion Tenet

An amazing recreation of the time inversion in tenet.

The Foreign Contribution (Regulation) Amendment Bill, 2020

The Foreign Contribution (Regulation) Amendment Bill, 2020 was introduced in Lok Sabha on September 20, 2020. The Bill amends the Foreign Contribution (Regulation) Act, 2010. The Act regulates the acceptance and utilisation of foreign contribution by individuals, associations and companies. Foreign contribution is the donation or transfer of any currency, security or article (of beyond a specified value) by a foreign source.

Prohibition to accept foreign contribution: Under the Act, certain persons are prohibited to accept any foreign contribution. These include: election candidates, editor or publisher of a newspaper, judges, government servants, members of any legislature, and political parties, among others. The Bill adds public servants (as defined under the Indian Penal Code) to this list. Public servant includes any person who is in service or pay of the government, or remunerated by the government for the performance of any public duty.

Transfer of foreign contribution: Under the Act, foreign contribution cannot be transferred to any other person unless such person is also registered to accept foreign contribution (or has obtained prior permission under the Act to obtain foreign contribution). The Bill amends this to prohibit the transfer of foreign contribution to any other person. The term ‘person’ under the Act includes an individual, an association, or a registered company.

Aadhaar for registration: The Act states that a person may accept foreign contribution if they have: (i) obtained a certificate of registration from central government, or (ii) not registered, but obtained prior permission from the government to accept foreign contribution. Any person seeking registration (or renewal of such registration) or prior permission for receiving foreign contribution must make an application to the central government in the prescribed manner. The Bill adds that any person seeking prior permission, registration or renewal of registration must provide the Aadhaar number of all its office bearers, directors or key functionaries, as an identification document. In case of a foreigner, they must provide a copy of the passport or the Overseas Citizen of India card for identification.

FCRA account: Under the Act, a registered person must accept foreign contribution only in a single branch of a scheduled bank specified by them. However, they may open more accounts in other banks for utilisation of the contribution. The Bill amends this to state that foreign contribution must be received only in an account designated by the bank as “FCRA account” in such branch of the State Bank of India, New Delhi, as notified by the central government. No funds other than the foreign contribution should be received or deposited in this account. The person may open another FCRA account in any scheduled bank of their choice for keeping or utilising the received contribution.

Restriction in utilisation of foreign contribution:. Under the Act, if a person accepting foreign contribution is found guilty of violating any provisions of the Act or the Foreign Contribution (Regulation) Act, 1976, the unutilised or unreceived foreign contribution may be utilised or received, only with the prior approval of the central government. The Bill adds that the government may also restrict usage of unutilised foreign contribution for persons who have been granted prior permission to receive such contribution. This may be done if, based on a summary inquiry, and pending any further inquiry, the government believes that such person has contravened provisions of the Act.

Renewal of license: Under the Act, every person who has been given a certificate of registration must renew the certificate within six months of expiration. The Bill provides that the government may conduct an inquiry before renewing the certificate to ensure that the person making the application: (i) is not fictitious or benami, (ii) has not been prosecuted or convicted for creating communal tension or indulging in activities aimed at religious conversion, and (iii) has not been found guilty of diversion or misutilisation of funds, among others conditions.

Reduction in use of foreign contribution for administrative purposes: Under the Act, a person who receives foreign contribution must use it only for the purpose for which the contribution is received. Further, they must not use more than 50% of the contribution for meeting administrative expenses. The Bill reduces this limit to 20%.

Surrender of certificate: The Bill adds a provision allowing the central government to permit a person to surrender their registration certificate. The government may do so if, post an inquiry, it is satisfied that such person has not contravened any provisions of the Act, and the management of its foreign contribution (and related assets) has been vested in an authority prescribed by the government.

Suspension of registration: Under the Act, the government may suspend the registration of a person for a period not exceeding 180 days. The Bill adds that such suspension may be extended up to an additional 180 days.

Jhum cultivation

What is Jhum cultivation?

Farmers slash and burn a patch of land, start growing food crops.
When soil fertility declines they shift to another place, burning the jungle again.
For various names for Jhum
Favor of Jhum cultivation

Uses forest’s natural cycle of regeneration.
Organic farming, doesn’t use pesticides or chemical fertilizers. Trees burned to provide potash to the soil
Cooperation: after jhuming, the land distributed among farmers.
Jhum causes only temporary loss of jungle. Because once monsoon over, the farmers abandon the land. Jungle regenerates quickly.

The Jhum cycle normally runs for around 6-10 years. i.e. when farmers return to the same patch of land and burn forest again.
During those 6-10 years, same jungle provide forest produce to the tribals.
Contrary to that, monoculture plantation causes permanent loss of forest, due to chemical inputs. so once, you cut down a forest to raise monoculture plantation, you cannot reconvert the same land into natural forest again.

Jhuming done in steep hill slopes where sedentary cultivation not possible. So it’s a reflex to physiographical characters of the North east.

overall, Jhum economically productive + ecologically sustainable

Against Jhum cultivation

If you leave the jungle for ten years, it’ll regenerate. But nowadays farmers come back in jut ~5 years. Not enough time for the forest to regenerate.
North eastern forest are major carbon sinks, home to biodiversity. Must be protected.
Jhum farming families always suffer food, fuel and fodder problems, leading to poverty and malnutrition.
tons of biomass gets loss due to burning of tress.

Tree burning leads to:
higher CO2, NO2 and other Greenhouse gases (GHGs). This wasn’t an issue in ancient times (when there was no industrialization). But we cannot afford more GHG in modern era.
higher run off of rainwater. hence draught, drinking water shortage.
we cannot find oaks, bamboo and teak forests in many regions of North East- only deciduous scrubs left. this erodes biodiversity of the region.

soil erosion, siltation in dams.

Too much Democracy impacting Economic Freedom

Research paper on Partial vaccination

Abstract

This review article outlines the key concepts in vaccine epidemiology, such as basic reproductive numbers, force of infection, vaccine efficacy and effectiveness, vaccine failure, herd immunity, herd effect, epidemiological shift, disease modeling, and describes the application of this knowledge both at program levels and in the practice by family physicians, epidemiologists, and pediatricians. A case has been made for increased knowledge and understanding of vaccine epidemiology among key stakeholders including policy makers, immunization program managers, public health experts, pediatricians, family physicians, and other experts/individuals involved in immunization service delivery. It has been argued that knowledge of vaccine epidemiology which is likely to benefit the society through contributions to the informed decision-making and improving vaccination coverage in the low and middle income countries (LMICs). The article ends with suggestions for the provision of systematic training and learning platforms in vaccine epidemiology to save millions of preventable deaths and improve health outcomes through life-course.

Introduction

The benefits of vaccination, one of the most cost-effective public health interventions, have not fully reached target beneficiaries in many low- and middle-income countries (LMICs).[1] Though the field of vaccine research and vaccinology has received a lot of attention since the discovery of the smallpox vaccine by Edward Jenner (1749-1823) in 1798, more than two centuries later, an estimated 20% of deaths among children aged less than 5 years occur due to diseases preventable by currently licensed vaccines.[2,3] Since the discovery of smallpox vaccine, a number of vaccines have become available. “Vaccine research and vaccinology” had witnessed a sort of ‘renaissances in vaccine research and uses’ in the early 1970s and 1980s, and now in the 21st century there are licensed vaccines against nearly 27 agents and ongoing research on candidate vaccines against nearly 130 agents.[1]

There is increasing recognition of the role of vaccines as proven lifesaving interventions and that of the epidemiological principles in maximizing the benefits of vaccines and vaccination. While vaccinology delves into understanding how vaccines work, epidemiology helps to ascertain whether a particular vaccine is needed in targeted population (or age group) or not? For physicians and vaccine users alike, epidemiology and immunology are two important fields in medical science and public health, which helps in the better appreciation of the promise and potential of vaccines. While immunology is essential for understanding vaccine-host interactions, epidemiology is essential for understanding the implications of a vaccination program on the community and individuals. “Vaccine epidemiology” could be described as an interface between public health, basic medical sciences, and clinical medicine aimed at maximizing the benefit of existing knowledge in these areas.

The learning and study of vaccine epidemiology could help in the following: To make decisions on how to choose vaccines for inclusion in a public health program; to assess the disease burden; to identify target pathogens for vaccine research; to identify sources and transmission pathways of disease-causing agents; to determine vaccination strategies; to design disease-specific control, elimination, and eradication strategies; to monitor performance indicators; to take steps to improve surveillance; and to measure the progress and impact of vaccination strategies.

This review article aims to outline the basic concepts and key principles of vaccine epidemiology, and to briefly describe how vaccination program managers and vaccinologists could use this knowledge and understanding in their respective fields of work.

Go to: Historical Background The terms “vaccine” and “vaccinology” came into use soon after Edward Jenner discovered the smallpox vaccine. Jenner called the smallpox vaccine “variola vaccinae.” For his contribution, Jenner is often referred to as the “Father of Vaccinology” (though this epithet is sometimes also used for Louis Pasteur). The word “vaccine” originated from vacca, a Latin term for the cow.[4] The credit for the first use of the term “vaccine” goes to Swiss physician Louis Odier (1748-1817), and the terms “vaccination” and “to vaccinate” were first used by Richard Dunning (1710- 1797).[5]

Epidemiology, which literally means “the study of what is upon the people,” is derived from the Greek epi meaning “upon, among,” demos meaning “people,” and logos meaning “study or discourse.” Physicians from the times of Hippocrates (460-370 BC) tried to understand the pattern of diseases in the community, though the term “epidemiology” was first used to describe the study of epidemics in 1802 by the Spanish physician Villalba in the Epidemiología Española.[6] In modern times, John Snow (1813-1858) and William Farr (1807-1883) pioneered the work on epidemiology and are often referred as one of the “fathers of modern epidemiology.”[7,8] Epidemiology, though practiced from earlier times than vaccinology, gained attention and prominence in the 19th century. Now, the practice of vaccinology has become closely linked with that of epidemiology.

Go to: Key Concepts in Vaccinology

A vaccine is “an inactivated or attenuated pathogen or a component of a pathogen (nucleic acid, protein) that when administered to the host, stimulates a protective response of the cells in the immune system,” or it is “an immune-biological substance designed to produce specific protection against a given disease.”[9] The process of administering the vaccine is called vaccination. In other words, vaccination is the process of protecting susceptible individuals from diseases by the administration of a living or modified agent (e.g., oral polio vaccine), a suspension of killed organisms (as in pertussis), or an inactivated toxin (as in tetanus). Immunization is “the artificial induction of active immunity by introducing into a susceptible host the specific antigen of a pathogenic organism.”[9] However, immunization and vaccination are often used interchangeably. Vaccinology combines the principles of microbiology, immunology, epidemiology, public health, and pharmacy, amongst other.

The aim of vaccination is to protect individuals who are at risk of a disease. The children, the elderly, immune-compromised individuals, people living with chronic diseases, and people living in disease-endemic areas are those most commonly at risk. Vaccination is a common strategy to control, eliminate, eradicate, or contain disease (i.e., mass immunization strategy). If one wishes to learn about and understand vaccines, vaccination, and immunization programs, one needs to start with the understanding of key terms such as “antigen,” “antibody,” “immunoglobulins,” and “antisera,” among others. These are often described in the textbooks on this topic and therefore not covered in this article.

A vaccine is different from immunoglobulin in that the vaccines help in developing protective antibodies in the body of the individual to whom these are administered, and protection is available after a lag period of a few weeks to several months. However, immunoglobulin provides immediate protection. The vaccine administration is followed by two types of immune responses: Primary and secondary [Figure 1].[9,10]

There are different types of vaccines: Live, killed, conjugate, component, and recombinant vaccines. While live vaccines provide protection after the administration of a single dose (though not always), the nonlive (or killed) vaccines usually require multiple doses for a satisfactory primary response. A minimum of 4 weeks’ interval is required between successive doses, though a longer interval (often, 8 weeks is considered optimal) results in higher antibody levels. The booster doses are generally given 6 or more months after the completion of the primary series. The booster doses have rapid and higher antibody response, a higher affinity for antibody production, and provide longer duration of protection (this is linked to secondary immune response).[11]

The antibody responses to vaccines are usually identified by “the correlates of protection,” an immune response that is responsible for and statistically interrelated with protection and usually linked to B-cell dependent response. Though, for a number of new vaccines, it is assumed that T-cells also play a role in correlates of protection. The correlates of protection are identified by animal challenge models and efficacy trials.[12]

Go to: Key Concepts in Epidemiology

Epidemiology pinpoints the weak links in the chains, sources, and transmission pathways of the pathogen so that the interventions can be directed. The understanding of epidemiology is required from the very early stage of priority-setting for disease burden, understanding the basis of correlates of protection, development of vaccines, evaluating different vaccination strategies including epidemiological and economic modeling, deciding national vaccination strategies, developing surveillance mechanisms, impact assessment, and designing vaccine introduction strategies.

The term “disease burden” or burden of disease (BoD) occupies a key place in epidemiology. The BoD could be measured by incidence or prevalence of a disease (prevaccine and postvaccine); severity/mortality (measured as case fatality ratio, hospitalization, and disease sequelae); disability [measured by disability-adjusted life years (DALYs)] and quality-adjusted life years (QALYs)]; economics (measured by cost-effectiveness, cost benefit, and cost utility); and social aspects (measured by societal disruption, economic disruption, and household impact).[13] The key concepts and study designs (i.e., cross-sectional, case-control, nested case-control, cohort studies) to understand epidemiology (disease occurrence and trends) are well, documented and thus not described in this article.[14,15,16]

However, vaccine probe studies requires special mention here, a vaccine probe study is a randomized cluster trial of a vaccine in which, usually, vaccine effectiveness (in other trials, usually efficacy is assessed) endpoints are used. The difference in the incidence of disease between vaccinated and unvaccinated children represents the vaccine-preventable disease burden. These are technically vaccine-effectiveness trials and have been used to measure the vaccine-preventable proportion/incidence of clinically (not microbiologically) defined outcomes. This approach has been used successfully in several countries for studies on Haemophilus influenzae type b (Hib) conjugate and pneumococcal conjugate vaccines.[17,18]

Go to: Vaccine Epidemiology

Vaccine epidemiology is the study of the interactions and effects of vaccines (and vaccination programs) on epidemiology of vaccine preventable diseases. Understanding the pattern of disease by geographical, rural-urban, and gender variations, linkage between disease burden and immunization coverage is based on principles of epidemiology. Which time of the year the polio mass immunization campaign should be conducted? For conducting mass campaigns, which age group should be targeted? Where should immunization efforts be concerted? Why do outbreaks occur? Why is it that some children do not suffer disease even though they have not received any vaccination? These are some of the questions answered through the application.

Vaccine efficacy and effectiveness

Vaccines have effect at both individual and population levels. The “biological or individual level effect” of vaccines includes effects on susceptibility (VEs), on infectiousness (VEi), and on disease progression (VEp). The “population level effects” of vaccination depend on the coverage and distribution of the vaccines, as well as on how well different groups mix with each other.[29,30,31] These effects could result from the biologic as well as behavioral effects of the vaccination. Overall, the public health effect of vaccination programs depends on the effect in both vaccination and the unvaccinated population. This gives at least three types of population level effects of vaccination:

Indirect effect: The population level effect of widespread vaccination on people not receiving vaccine

Total effect: Combination of population level effect and effect of vaccination on individuals receiving vaccine

Overall public health effect: The effect of vaccination program based upon weighted average of indirect effect on the individual not receiving vaccine and total effect on individual receiving vaccination.

In this context, the terms “vaccine efficacy,” “vaccine effectiveness,” and “program effectiveness” are commonly used. Vaccine efficacy is the percentage reduction in disease incidence attributable to vaccination (usually) calculated by means of the following equation:

VE (%) = (RU - RV)/RU × 100

where RU = the incidence risk or attack rate in unvaccinated people and RV = the incidence or attack rate in vaccinated people.[29,30]

The equation for vaccine efficacy can be reformulated as:

VE = 1 -RV/RU × 100

where RV/RU is the relative risk or rate ratio in vaccinated and unvaccinated people.

The vaccine efficacy is measured by observational studies under field conditions within a vaccination program or measured by trials conducted under normal program conditions. The vaccine efficacy for a number of vaccines is known, such as Measles 90-95%; mumps: 72-88%; and rubella 95-98%.[32,33] In vaccine trials, the vaccine's efficacy (among other things, including safety) is assessed. This is an important criterion for licensing of the vaccines and for making decisions on programmatic use. Vaccine efficacy is dependent on internal or individual factors, for example the efficacy of the measles vaccine depends on the presence of inhibitory maternal antibodies, the immunologic maturity of the vaccine recipient, and the dose and strain of the vaccine virus.[34]

Vaccine effectiveness is the sum of the reduction in the clinical events that might be expected to be associated with the disease.[28,29] Under program-based conditions, the effectiveness of the measles vaccine depends on the coverage, cold chain maintenance, correct injection techniques and safety, inaccurate recordkeeping/recall resulting in misclassification errors, and population-specific factors [human immunodeficiency virus (HIV) infection, malnutrition, etc.]. The most commonly used study design to assess a vaccine's effectiveness is a retrospective case-control analysis, and the odds ratio thus obtained can be used to calculate vaccine effectiveness, as follows:

Effectiveness = (1-OR) × 100

Vaccine effectiveness could be assessed by observational studies: Cohort studies, household contact study, case-control study and screening. How the information from screening could be used for estimating of vaccine efficacy is shown in Figure 2.[35,36]

Vaccine efficacy and effectiveness have often been used interchangeably in scientific literature. Vaccine effectiveness is often referred to as vaccine efficacy in field conditions. In other words, vaccine effectiveness is a combination of vaccine efficacy and field conditions such as coverage, immune status of population, and conditions under which the vaccine was administered (cold chain). In general, efficacy is higher than effectiveness. However, vaccines that show herd effect could have higher effectiveness than vaccine efficacy. For example, under program conditions, vaccine effectiveness is lower than vaccine efficacy, while herd effect improves effectiveness and can take it above efficacy. If analyzed from an outbreak, the formula for estimation of vaccine effectiveness is: Attack rate among vaccinated (ARV) vs attack rate among unvaccinated (URU). The formula used for assessing vaccine efficacy with this information is: Vaccine Efficacy (VE) = (ARU-ARV)/ARU*00.[35,36]

The “program effectiveness” refers to “the effectiveness of all antigens in an immunization program at implementation level at district, state and national levels.” The program effectiveness is also assessed by analyzing the trends in the occurrence of vaccine-preventable diseases (or VPDs) in identified settings and situation, before and after vaccine introductions. Overall mortality reduction is often considered as an indicator of vaccine program effectiveness/impact. Program effectiveness is the combination of more than one vaccine's effectiveness. Impact is the population level effect of a vaccination program, which depends on many factors, including vaccine efficacy, herd immunity, and effectiveness.

Go to:

Study Designs to Assess Vaccine Efficacy and Program Effectiveness Serological and epidemiological studies can be used to determine vaccine efficacy and program effectiveness with minor methodological adoptions.[9,15,16,18,33,34,35,36] Among serological studies, two sub types of studies are utilized for vaccine efficacy: Seroconversion studies and seroprevalence studies. Seroconversion studies are useful in measuring the induction of an immune response in the host. In the absence of disease, it indicates the persistence of antibodies and immunity. These studies are particularly useful in choosing the appropriate age for vaccination. Seroprevalence studies monitor the prevalence of antibodies due to disease in the population and indicate the pattern of occurrence of diseases.

The epidemiological approaches measure the ARV and ARU in various settings. Thereafter, the formula suggested above could be used for estimating vaccine efficacy. The epidemiological study designs[9,15,16,18,33,34,35,36] include:

Double-blind, randomized, placebo-control trials: The ideal vaccine efficacy study is a clinical trial starting with persons susceptible to disease. However, such studies are not possible after the vaccine is licensed, as it becomes unethical to use placebo when the vaccine is of proven benefit

Observational cohort studies: These are conducted when the randomized-controlled trials or secondary attack rate trials are not ethically justified, or are not feasible due to low incidence of the disease, or there is a requirement for long-term follow-up for the calculation of efficacy (e.g., hepatitis B vaccination in neonates, or where the number of individuals is too large to follow up)

Case-control studies: These studies are most useful when personal immunization records are not generally available but some other sources such as records from clinics can be obtained. Case-control studies may be useful when prospective controlled trials are not feasible due to low incidence of disease

Stepped wedge design studies: These are used when previous studies have indicated that the intervention is likely to be beneficial and the public health needs to introduce the intervention precludes withholding it from a population. The intervention is introduced in phases, group by group, until the entire target population is covered. The groups form the unit of randomization

Outbreak investigations (Community-wide, total population, or population clusters): Such studies are best done when the outbreak is in a defined population, such as a village, town, city, or school

Secondary attack rates in families and/or clusters: The assessment of secondary attack rate in family members of the “index case” provides a good opportunity to assess vaccine efficacy

Screening of population: This method provides an estimate of vaccine efficacy if some other information is available. The formula used for assessing vaccine efficacy is given below and is used for assessing vaccine efficacy:

PCV = [PPV- (PPV*VE)]/[1-(PPV*VE)]

where PCV = proportion of cases occurring among vaccinated individuals; PPV = proportion of population vaccinated; and VE = vaccine efficacy. If any of the two values in this formula is known, the third value can be derived [Figure 2].

Cluster Survey Method: In some of the endemic areas, vaccine efficacy can be assessed, even in the absence of an outbreak, by using coverage survey methods.

Go to: Other Important Concepts in Epidemiology Vaccine failure When a person who has been fully vaccinated develops the disease against which she/he has been vaccinated, it is referred to as vaccine failure. This could be of two types-

Primary vaccine failure occurs when the recipient does not produce enough antibodies when first vaccinated. Infection can therefore occur at any time post vaccination. For example, this occurs in about 10% of those who receive the measles, mumps, and rubella (MMR) vaccine[37]

Secondary vaccine failure occurs when adequate protective levels of antibodies are produced immediately after the vaccination, but the levels fall over time. The incidence of secondary vaccine failure therefore increases with time after the initial vaccination and hence booster doses are required. This is a characteristic of a number of the inactivated vaccines.[37]

Herd immunity and herd effect

Herd immunity may be defined as the resistance of a group or a community in total, against the invasion and spread of an infectious agent as a result of a large proportion of individuals in the group being immunized. Herd immunity or contact immunity develops in the case of certain live vaccines (e.g., OPV), wherein the nonvaccinated individuals also develop immunity to the pathogen just by coming in contact with the vaccinated individual.[38]

The level of herd immunity can be assessed through cross-sectional and longitudinal serological surveys. The serological surveys are usually based on serum or saliva in viral infections and activated T-cells for bacterial and protozoal infections. There are a number of quantitative assays, too.[39]

Additionally, immunological and disease surveillance methods provide the empirical base for the analysis and interpretation of herd immunity. Mathematical and statistical methods play an important role in the analysis of infectious disease transmission and control. They help to define both what needs to be measured, and how best to measure and define epidemiological quantities. The level of herd immunity can be measured by reference to the magnitude of reduction in the value of Ro.[22]

Herd immunity threshold (H) is defined as the minimum proportion to be immunized in a population for elimination of infection.

H = 1 - 1/Ro = (Ro -1)/Ro As the immunization coverage increases, the incidence and prevalence rates may decrease not only due to the direct effect of immunization per se but also because of indirect effects, such as the development of herd immunity and herd effect.[38,40]

“Herd effect” or “herd protection” is “the reduction of infection or disease in the unimmunised segment as a result of immunising a proportion of the population” or is “the change induced in epidemiology (incidence reduction) among unvaccinated members when a good proportion is vaccinated.” Herd effect is seen only for infections where humans are the source, and it extends beyond the age the vaccine is given, i.e., Haemophilus influenzae type B (Hib) vaccine is given to infants and protected other under-5 children, flu vaccine to children and beneficial effect among other family members.

Epidemiologic shift or transition

Epidemiological shift or transition denotes the change in the pattern of disease in a specified population. The impact on the person characteristics of a disease is the shift in the age of occurrence and severity of the diseases as observed consistently in communities with partial immunization coverage or immunization coverage for specific age groups only. A number of factors including the age at the time of vaccination, target population for vaccination, serotypes covered by the vaccines (where the disease in question is caused by multiple serotypes), and overall vaccination coverage may affect the epidemiological shift or transition.[41,42]

The phenomenon has importance in diseases such as hepatitis A, rubella, and varicella, wherein the severity of disease worsens with advancing age. It also has significance in diseases where multiple serotypes are associated with the diseases such as pneumococcal diseases and when targeting specific serotype by vaccine may lead to the emergence of other types of serotypes. The epidemiological shift or transition sometimes may offshoots the benefits accrued by the vaccination program. This showcases the need for tracking the epidemiological changes in the vaccination programs and initiating appropriate corrective measures.

One of the well-documented example of epidemiological shifts has been documented from Greece, following the introduction of MMR vaccine in public health program of the country. When the MMR vaccine was introduced in 1975 in Greece, the coverage with the vaccine was around 50-60% of the cohort, which reduced the incidence of diseases in the targeted population; however, shifted the average age of infection to older population. However, the susceptible cohort of un-vaccinated continued to increase over period of time with epidemiological shift to older age groups. By the early 1990s, specially those unvaccinated girls reached in the reproductive age group, still susceptible to rubella virus disease. In such cases, if the infections happened during the time of pregnancy, it led to development of congenital rubella syndrome (CRS) in fetus/infants. In 1993, it was noted that Greece had the highest incidence of congenital rubella syndrome (CRS).[42] This example highlights the need and importance for high coverage at the time of vaccine introduction and sustenance of the coverage in the subsequent cohorts. This situation is sometimes referred to as “perverse outcome,” where disease severity increases with age at infection: Vaccination can increase the burden of severe diseases, by raising the average age of infections. The total number of infections falls but the total number of severe disease increases, e.g., CRS, measles, encephalitis, and orchitis due to mumps.

Go to: Vaccine-preventable Disease Surveillance Disease surveillance is another public health and epidemiology tool. A functioning disease surveillance system helps in understanding disease epidemiology before vaccines are introduced. Thereafter, it guides how well the vaccination program is doing in reducing the BoD. It helps in decisionmaking on the introduction of vaccines and also in assessing the impact of interventions. Unfortunately, the disease surveillance system in the majority of the LMICs requires a major boost.

Go to: Disease Modeling The models are often referred to as “tools for thinking and simplification of systems,” suitable for analysis.[43]

Epidemiology aims to measure the disease burden; however, where measurement is not practical, estimates must be developed. The modern epidemiological methods and disease modeling have reached the level where accurate projection can be made based on existing knowledge and information. The estimates derived from various sources are often used in vaccination programs. The estimates are used for decisionmaking at local levels (i.e., state and national levels), for deriving estimates for neighboring countries (with similar settings) and for global (or international) levels. The estimates, if done with similar methods can provide useful information for interstate, intercountry, and interdisease comparisons, to observe the disease trend over a period of time, and for comparison of choices between intervention versus none versus others

In vaccination programs, a number of models are used: A static or decision analysis model is used on the assumption of a constant force of infection (or fixed risk). These models are more commonly used for noninfectious diseases. The static models are usually applied to a single cohort[45]

Markov models[46]

Dynamic model used for infectious diseases. Suspected, infected, and recovered (SIR) approach is an example of a dynamic model. These models are applied to multiple cohorts.[47]

Economic evaluation Economic evaluation in healthcare addresses the question whether an intervention or procedure is worth doing when compared with other possible uses of the same resources.[44] This is based on the premise that resources are finite and there are opportunity costs. In such analysis, both costs (resources used) and outcomes (benefits) are considered. There are number of analyses including cost-effective analysis, cost-benefit analysis, cost analysis, and cost utility analysis.

Go to: Immunization Program Assessments and Evaluations It is imperative to ensure the quality of immunization services is evaluated and assessed on a regular basis. The epidemiological methods provide useful tools for such evaluations.

Thirty cluster survey: This is standard World Health Organization (WHO) methodology to determine immunization coverage based on a survey of small number of individuals (for example, 210 in 30 clusters of seven children each). The home visits are made and a immunization record or history is taken for children aged 12-23 months. The survey provides fairly correct information about immunization coverage in the area. However, it is important that these clusters are selected based on standardized methodology and statistical tools[48]

Seventy-five-household survey: In this approach, 75 households near the health facility are surveyed. This methodology follows the notion that the households closest to the facilities can provide the best estimates of immunization coverage[49]

Missed-opportunity survey, Lot quality assurance survey (LQAS), the multiple indicator cluster survey (MICS), and coverage evaluation surveys (CES) are the other methods.[49]

Go to: Application of Vaccine Epidemiology in Vaccination Programs Vaccine epidemiology, as described in the earlier sections, is a multidisciplinary science. It has a role to play from vaccine research (proof-of-concept stage and then in clinical trials), in decisionmaking on new vaccine introduction, and once vaccines are introduced in the post-marketing surveillance and other aspects. The practice of vaccinology is gathering momentum since the first immunization schedule was published by the WHO in 1961.[50] Now in the 21st century, there are more licensed vaccines, more in the pipeline, more number of people than ever receive vaccines. There is an increasing amount of research in laboratories, deliberations in academic institutions, and policy discourses in ministries of health about vaccines and vaccination schedules. There is an increasing awareness within the general public about vaccines and vaccination schedules.

One of the important development in the last 2 decades has been that the electronic media and the Internet have empowered people with information. The information received from various sources on the Internet is mostly useful for parents and the general public but is not always correct. At times, it reflects one sided view, and people with vested interests may misuse the information and media. The risk of such incomplete information has been reflected in some of the recent outbreaks of measles in European countries where the Internet has been a major source of information, and people used this source for decisionmaking. Such misinformation has affected the adoption of human papillomavirus (HPV) vaccination in a few countries.[51,52] These examples reflect the two sides of technology, which can help in increasing coverage of vaccines but could also spread misinformation which can lead to disease outbreaks.

The incidences of “vaccine refusal” or “vaccine hesitancy” are increasing.[53] This is an area in which the knowledge and understanding of vaccine epidemiology could help in improving immunization coverage (or at least prevent undesired fall in immunization coverage). The vaccine epidemiology can help in responding to the misinformation and addressing the challenge. Vaccine epidemiology can provide guidance in understanding which diseases are common in which parts of the world and therefore help in decisionmaking about which vaccine should be received by the people traveling to particular endemic countries. It guides in the selection of vaccines for special target groups, i.e., pregnant women, the elderly, and in the changing context.

The disease surveillance system is often used to measure the impact of vaccination programs on disease burden. The vaccine preventable diseases surveillances system could provide useful insight on the benefits of vaccination and is an important tool for programmatic modifications and advocacy. The National Immunization Technical Advisory Groups (NITAGs) use vaccine epidemiology for decision making. The national vaccination policies and immunization guidelines need to be informed by the vaccine epidemiology.

There are important roles of vaccine epidemiology in reducing morbidity and mortality from vaccine-preventable diseases. This knowledge could be best utilized by policy makers for immunization program decisionmaking and by family physicians and public health specialists for advising individuals on the benefits of vaccination.

In LMICs there is limited capacity for training in vaccinology and epidemiology. There are very few training opportunities and courses that teach vaccine epidemiology. It is a paradox that countries requiring maximum capacity have very limited opportunity. This affects both vaccine research and decisionmaking.

In the absence of sufficient capacity, the country program managers in LMICs often have to rely on international experts for decisionmaking. This adversely affects the reputation and credibility of the country's program managers and raises questions regarding the decisionmaking process, contributing to the delay in the benefits of proven interventions reaching those who are most susceptible to vaccine-preventable diseases.

Go to: Conclusion The understanding of vaccine epidemiology has potential to save additional lives from vaccine preventable diseases and improve health outcomes through life course. The vaccine epidemiology has definitive role in extending the benefits of vaccines to additional populations and in the selection of target groups for vaccination, amongst other. However, systematic efforts would be needed to translate this knowledge into actions. The mechanisms and institutional capacity has to be built into low and middle income countries (LMICs) on vaccine epidemiology. The national governments and international development partners need to support and promote courses and training programs for vaccine epidemiology, and the academic communities need to work together. Vaccine epidemiology should be part of key modules in the teaching of undergraduate and postgraduate medical students. Public-health program managers and policy makers should be trained in vaccine epidemiology through continued medical education and on-the-job training programs.

Tenet movie review

Having more than proved his worth,CIA superspy The Protagonist (John David Washington) is inducted into secret organisation Tenet, on the trail of bullets that go backwards in time. From there he finds himself facing off against arms dealer Andrei Sator (Kenneth Branagh) in a bid to avert World War III.

By Alex Godfrey | Posted 21 Aug 2020 Release Date: 16 Jul 2020

The blams come thick and fast. Tenet, in fact, might be Christopher Nolan’s blammiest film yet. BLAM! A terrifying thing just happened. BLAM! A shocking moment of revelation. BLAM! Here’s a speedboat. (There really is a massive blam accompanying an otherwise ordinary shot of two people on a speedboat.) It’s not even Hans Zimmer this time — here the great Ludwig Göransson (Black Panther, The Mandalorian) is on scoring duties, making it all his own (you will nod your head intensely) but without ever scrimping on the blams. Because if a Christopher Nolan film doesn’t sound like the end of the world, then something’s wrong. And this one really is about the end of the world.

We’re told early on — defiantly and resolutely — that this is not a film about time-travel. There are a handful of instances in Tenet where one character lays things out to another, each time telling them it’s okay if they don’t quite get it. “Don’t try to understand it,” says Clémence Poésy’s Laura, Tenet’s Q to John David Washington’s James Bond, as she introduces him to backward bullets (they go back in time… don’t try to understand it) and gives him a brief primer. It’s not time-travel, she tells him, it’s “technology that can reverse an object’s entropy”. In other words, Christopher Nolan wants you to know that this is not Back To The Future. This is serious business. This is about the prevention of World War III. “Nuclear holocaust?” asks Washington’s protagonist. No, she says — this is worse.

This scene, Nolan setting out his stall, is scored sumptuously, romantically — it’s one big swoon, and it speaks volumes. Despite a complex relationship serving as the film’s broken heart (courtesy of Kenneth Branagh’s arms-dealing oligarch Andrei and his estranged and abused wife Kat, played by Elizabeth Debicki), Nolan’s great love affair, of course, is with time itself. From Memento’s muddied, memory-straining recollections to Dunkirk’s triple-pronged timeline and Interstellar’s generational rifts, he can’t get enough of the stuff, and Tenet is awash in it. It’s not a plot device — it’s the thing itself, something to be explored, investigated, played with, twisted, bent.

Nolan has made his own Bond film here, borrowing everything he likes about it, binning everything he doesn’t, then Nolaning it all up.

And yet: this is an action film. It opens with a brutal, prolonged siege at the Kiev Opera House, in which people fight for their lives and lose, in which all hell breaks loose, and in which Göransson and Nolan’s sound designers intend to deafen you. You have Washington and Robert Pattinson bungee-jumping up and into a building (and that’s without any of the time-bending). You have a lean and mean kitchen fight in which a cheese grater is deployed (and not for cheese). You have a 747 being blown up, you have a thrilling car chase (which does feature some time-bending), and extended set-pieces in which your eyes will see things they haven’t quite seen before. For the most part, there are no Hollywood hysterics; it is big — often very big — but not bombastic.

Tenet is Bond without the baggage. Filmed in Italy, Estonia, India, Norway, the UK and the US, it’s a globetrotting espionage extravaganza that does everything 007 does but without having to lean into the heritage, or indeed the clichés. Just as with Indiana Jones, for which George Lucas persuaded Bond fan Steven Spielberg they could create their own hero instead of piggybacking on someone else’s, Nolan has made his own Bond film here, borrowing everything he likes about it, binning everything he doesn’t, then Nolaning it all up (ie: mucking about with the fabric of time). And while Washington — never not magnetic, every second of this film – isn’t a suave playboy in the slightest, he has the swagger — and the odd wisecrack. “Easy,” he says in response to some light manhandling from one of Andrei’s security goons. “Where I’m from, you buy me dinner first.” In the same sequence, Andrei — a big bad if ever there was one — asks him: “How would you like to die?” Elsewhere we meet an arms dealer who casually swigs his whiskey while he has a gun to his head. This is absolutely the same playground that 007 runs around in, with the same toys. It just feeds it all through a physics machine.

For the most part, that’s welcome. “Try to keep up,” one character says in regards to the mechanics of it all. “Does your head hurt?” another asks later. Somebody is told they need to stop thinking in linear terms. No doubt some big brains will be fine with all of this — and will be able to follow the plot — but for the rest of us, Tenet is often a baffling, bewildering ride. Does it matter? Kind of. It’s hard to completely invest in things that go completely over your head. The broad strokes are there, and it’s consistently compelling, but it’s a little taxing. No doubt it all makes sense on Nolan’s hard drive, but it’s difficult to emotionally engage with it all.

If that’s even what the film wants us to do. These are great actors — Washington, Pattinson, Branagh and Debicki are all immensely watchable — but only towards the end, as things begin to pay off, do you really get the chills here and there. For the most part, everybody’s on a mission, doing their job, the film barely stopping to breathe, certainly not to take any sentimental detours. And nobody involved looms larger than Nolan himself. This is a film engineered for dissection and deconstruction. Just as Inception was, this is an M.C. Escher painting, but folded, origami-like, and with holes poked into it for its own denizens to fall through. It may not be Back To The Future, but regardless, it has its cake, eats it, then goes back in time and eats it again. It may not be a hokey time-travel film, but that doesn’t mean Nolan can’t get his rocks off playing around with paradoxes.

And ultimately, for all of that, Tenet once again proves Nolan’s undying commitment to big-screen thrills and spills. There’s a lot riding on this film, to resurrect cinema, to wrench people away from their televisions, facemasks and all. It may well do the trick: if you’re after a big old explosive Nolan braingasm, that is exactly what you’re going to get, shot on old-fashioned film too (as the end credits proudly state). By the time it’s done, you might not know what the hell’s gone on, but it is exciting nevertheless. It is ferociously entertaining.

Once again seizing control of the medium, Nolan attempts to alter the fabric of reality, or at least blow the roof off the multiplexes. Big, bold, baffling and bonkers