People who habituate to stress show a repetition-induced response attenuation—neuroendocrine, cardiovascular, neuroenergetic, and emotional—when exposed to a threatening environment. But the exact dynamics underlying stress habituation remain obscure. The free energy principle offers a unifying account of self-organising systems such as the human brain. In this paper, we elaborate on how stress habituation can be explained and modelled using the free energy principle. We introduce habituation priors that encode the agent’s tendency for stress habituation and incorporate them in the agent’s (...) decision-making process. Using differently shaped goal priors—that encode the agent’s goal preferences—we illustrate, in two examples, the optimising behaviour of agents. We show that habituation minimises free energy by reducing the precision of goal preferences. Reducing the precision of goal priors means that the agent accepts adverse states. Acceptance or tolerance of adverse outcomes may explain why habituation causes people to exhibit an attenuation of the stress response. Given that stress habituation occurs in brain regions where goal priors are encoded, i.e., in the ventromedial prefrontal cortex and that these priors are encoded as sufficient statistics of probability distributions, our approach seems plausible from an anatomical-functional and neuro-statistical point of view. The ensuing formal and generalisable account—based on the free energy principle—further motivate our novel treatment of stress habituation. Our analysis suggests that stress habituation has far-reaching consequences, protecting against the harmful effects of toxic stress, but on the other hand making the acceptability of precarious living conditions and the development of the obese type 2 diabetes mellitus phenotype more likely. (shrink)

There is a steadily growing literature on the role of the immune system in psychiatric disorders. So far, these advances have largely taken the form of correlations between specific aspects of inflammation (e.g. blood plasma levels of inflammatory markers, genetic mutations in immune pathways, viral or bacterial infection) with the development of neuropsychiatric conditions such as autism, bipolar disorder, schizophrenia and depression. A fundamental question remains open: why are psychiatric disorders and immune responses intertwined? To address this would require a (...) step back from a historical mind–body dualism that has created such a dichotomy. We propose three contributions of active inference when addressing this question: translation, unification, and simulation. To illustrate these contributions, we consider the following questions. Is there an immunological analogue of sensory attenuation? Is there a common generative model that the brain and immune system jointly optimise? Can the immune response and psychiatric illness both be explained in terms of self-organising systems responding to threatening stimuli in their external environment, whether those stimuli happen to be pathogens, predators, or people? Does false inference at an immunological level alter the message passing at a psychological level (or vice versa) through a principled exchange between the two systems? (shrink)

BackgroundAntipsychotic-induced weight gain is a contributing factor in the reduced life expectancy reported amongst people with psychotic disorders. CYP2D6 is a liver enzyme involved in the metabolism of many commonly used antipsychotic medications. We investigated if CYP2D6 genetic variation influenced weight or BMI among people taking antipsychotic treatment.MethodsWe conducted a systematic review and a random effects meta-analysis of publications in Pubmed, Embase, PsychInfo, and CENTRAAL that had BMI and/or weight measurements of patients on long-term antipsychotics by their CYP2D6-defined metabolic groups.ResultsTwelve (...) studies were included in the systematic review. All cohort studies suggested that the presence of reduced-function or non-functional alleles for CYP2D6 was associated with greater antipsychotic-induced weight gain, whereas most cross-sectional studies did not find any significant associations. Seventeen studies were included in the meta-analysis with clinical data of 2,041 patients, including 93 poor metabolizers, 633 intermediate metabolizers, 1,272 normal metabolizers, and 30 UMs. Overall, we did not find associations in any of the comparisons made. The estimated pooled standardized differences for the following comparisons were PM versus NM; weight = –0.07, BMI = 0.40. IM versus NM; weight = 0.09 and BMI = 0.09. UM versus EM; weight = 0.01 and BMI = –0.08.ConclusionOur systematic review of cohort studies suggested that CYP2D6 poor metabolizers have higher BMI than normal metabolizers, but the data of cross-sectional studies and the meta-analysis did not show this association. Although our review and meta-analysis constitutes one of the largest studies with comprehensively genotyped samples, the literature is still limited by small numbers of participants with genetic variants resulting in poor or UMs status. We need further studies with larger numbers of extreme metabolizers to establish its clinical utility in antipsychotic treatment. CYP2D6 is a key gene for personalized prescribing in mental health. (shrink)

Language experience clearly affects the perception of speech, but little is known about whether these differences in perception extend to non-speech sounds. In this study, we investigated rhythmic perception of non-linguistic sounds in speakers of French and German using a grouping task, in which complexity was manipulated. In this task, participants grouped sequences of auditory chimeras formed from musical instruments. These chimeras mimic the complexity of speech without being speech. We found that, while showing the same overall grouping preferences, the (...) German speakers showed stronger biases than the French speakers in grouping complex sequences. Sound variability reduced all participants’ biases, resulting in the French group showing no grouping preference for the most variable sequences, though this reduction was attenuated by musical experience. In sum, this study demonstrates that linguistic experience, musical experience, and complexity affect rhythmic grouping of non-linguistic sounds and suggests that experience with acoustic cues in a meaningful context is necessary for developing a robust grouping preference that survives acoustic variability. (shrink)

The HealthyFood program offers members up to 25% cash back monthly on healthy food purchases. In this randomized controlled trial, we tested the efficacy of financial incentives combined with text messages in increasing healthy food purchases among HF members. Members receiving the lowest cash back level were randomized to one of six arms: Arm 1 : 10% cash back, no weekly text, standard monthly text; Arm 2: 10% cash back, generic weekly text, standard monthly text; Arm 3: 10% cash back, (...) personalized weekly text, standard monthly text; Arm 4: 25% cash back, personalized weekly text, standard monthly text; Arm 5: 10 + 15%NET cash back, personalized weekly text, standard monthly text; and, Arm 6: 10 + 15%NET cash back, personalized weekly text, unbundled monthly text. In the 10 + 15%NET cash back, the cash back amount was the baseline 10% plus 15% of the net difference between healthy and unhealthy spending. The generic text included information on HF and healthy eating, while the personalized text had individualized feedback on purchases. The standard monthly text contained the cash back amount. The unbundled monthly text included the amount lost due to unhealthy purchases. The primary outcome was the average monthly percent healthy food spending. Secondary outcomes were the percent unhealthy food spending, and the percent healthy and unhealthy food items. Of the members contacted, 20 opted out, and 2841 met all inclusion criteria. There were no between-arm differences in the examined outcomes. The largest mean difference in percent healthy spending was between Arm 1 and Arm 2, and the largest mean difference in percent unhealthy spending was also between Arm 1 and Arm 2, but no differences were statistically significant after correction for multiple comparisons. None of the tested financial incentive structures or text strategies differentially affected food purchasing. Notably, more than doubling the cash back amount and introducing a financial disincentive for unhealthy purchases did not affect purchasing. These findings speak to the difficulty of changing shopping habits and to the need for innovative strategies to shift complex health behaviors. NCT02486588 Increasing Engagement with a Healthy Food Benefit. The trial was prospectively registered on July 1, 2015. (shrink)

In “Missing the Forest for the Trees: Aduhelm, Accelerated Approvals & the Agency,” Dr. Matthew Herder argues that agency capture and politicized discretion drive delays in confirmatory trials of accelerated approval drugs amongst other concerns at US Food and Drug Administration (FDA). In highlighting this important problem and offering nuanced insight into agency workings based in part on interviews with twenty-three unnamed FDA officials and a three-drug case study, Dr. Herder suggests two innovative solutions. However, amidst broader debates balancing agency (...) expertise, data, and delegation, these proposed policy solutions would benefit from more corroborative evidence and consideration of institutional advantages within constitutional limits. (shrink)

While mass spectrometry (MS)‐based quantification of small molecules has been successfully used for decades, targeted MS has only recently been used by the proteomics community to investigate clinical questions such as biomarker verification and validation. Targeted MS holds the promise of a paradigm shift in the quantitative determination of proteins. Nevertheless, targeted quantitative proteomics requires improvisation in making sample processing, instruments, and data analysis more accessible. In the backdrop of the genomic era reaching its zenith, certain questions arise: is the (...) proteomic era about to come? If we are at the beginning of a new future for protein quantification, are we prepared to incorporate targeted proteomics at the benchside for basic research and at the bedside for the good of patients? Here, an overview of the knowledge required to perform targeted proteomics as well as its applications is provided. A special emphasis is placed on upcoming areas such as peptidomics, proteoform research, and mass spectrometry imaging, where the utilization of targeted proteomics is expected to bring forth new avenues. The limitations associated with the acceptance of this technique for mainstream usage are also highlighted. (shrink)

Child Labour in Kashmiri Society: A Socio-human Rights Study The Constitution of India guarantees fundamental rights and the full freedom to enjoy childhood. In spite of that millions of children are being put to arduous work for short and narrow gains. By 1989, the standards concerning children were brought together in a single legal instrument agreed to by the international community. It unambiguously spelt out the rights to which every child is entitled, regardless of place of birth, descent, sex, religion, (...) or social origin. A number of aspects, such as gender, family background, cultural acceptance, issues of health and recreation, the legal aspect and so on, have been covered. The life worlds of working children, legal protection to children from exploitation and the human rights perspective of child labour is the main focus of this article. (shrink)

Heart disease is the leading cause of death amongst adult Americans and has recently become a top killer worldwide. The direct costs of cardiovascular disease are projected to triple in the next 20 years, from $272.5 billion to $818.1 billion (Heidenreich et al. 2011). Although there has been a decreased incidence and prevalence of ischemic heart disease over the past several decades in the United States, heart failure remains a major cause of morbidity and mortality. In the United States, approximately (...) 500,000 to 700,000 new cases are identified each year (Lloyd-Jones et al. 2009). Heart failure is now the number one diagnosis leading to hospitalization. As such, it is an increasingly heavy economic burden on .. (shrink)

Work on Nyaya philosophy; includes Siddhāntamuktāvalī autocommentary and Dinakarī of Dinakarabhaṭṭa, 18th cent.

Contributed articles on self-realization.

Classical verse work on the fundamentals of Nyāya and Vaiśeṣika schools in Hindu philosophy.

Compendium of Indian epistemology and logic.

Yoga is a popular and beneficial evidence-based health practice. This book addresses the origins, explores yoga's evolution, and outlines current scientific research as well as contemporary discussions related to the possibilities as well as the politicization of this ancient Indian practice.

Flavin‐containing monooxygenases (FMOs), traditionally known for detoxifying xenobiotics, are now recognized for their involvement in endogenous metabolism. We recently discovered that an isoform of FMO, fmo‐2 in Caenorhabditis elegans, alters endogenous metabolism to impact longevity and stress tolerance. Increased expression of fmo‐2 in C. elegans modifies the flux through the key pathway known as One Carbon Metabolism (OCM). This modified flux results in a decrease in the ratio of S‐adenosyl‐methionine (SAM) to S‐adenosyl‐homocysteine (SAH), consequently diminishing methylation capacity. Here we discuss (...) how FMO‐2‐mediated formate production during tryptophan metabolism may serve as a trigger for changing the flux in OCM. We suggest formate bridges tryptophan and OCM, altering metabolic flux away from methylation during fmo‐2 overexpression. Additionally, we highlight how these metabolic results intersect with the mTOR and AMPK pathways, in addition to mitochondrial metabolism. In conclusion, the goal of this essay is to bring attention to the central role of FMO enzymes but lack of understanding of their mechanisms. We justify a call for a deeper understanding of FMO enzyme's role in metabolic rewiring through tryptophan/formate or other yet unidentified substrates. Additionally, we emphasize the identification of novel drugs and microbes to induce FMO activity and extend lifespan. (shrink)

Verse treatise, with autocommentary and supercommentaries, on the basic concepts and epistemology of Nyāya and Vaiśeṣika schools in Indic philosophy.

In this essay, the author presents the Martinican intellectual Edouard Glissant's Poétique de la Relation in a new frame by reading his text as it accomplishes a type of grand-scale theorizing. The notion of Relation in Glissant is followed in its various connections to a Marxian notion of dynamic totality. The Marxian/Hegelian subtext of Poétique is seen as productively revealing for reading Glissant both historically and theoretically. Glissant's theorizing of difference is shown to be an important contribution to contemporary revisions (...) of Marxian-informed thought. (shrink)

The half-century, which is the time that has elapsed since the publication of Wretched of the Earth , seems such a short period when one imagines its author in all his intellectual magnificence, his anguish, and the many details we all know of his short-lived reality. Dare one say, after the concept has long been declared “dead” that we imagine him as having been a live “author”? As I write this, the idea of various notable intellectuals and revolutionary movements could (...) come to mind in order for them to serve as interesting comparisons as we discuss and remember Fanon, his analyses of the colonial aftermath, and his many predictions, both explicit and implicit. However, the “death” of the author is, in fact, as Barthes’ polemical essay showed, a premise that empowers the text in its full potentiality well beyond the deism by which the identity of the author becomes the authority. Here, the liberation of the text joins up the enunciation with its “content” so to speak, or in Barthes’ words, reveals how Fanon “made of his very life a work for which his book was a model.” It is from this idea that I wish to see Fanon as incomparable. The reason to do so does not stem from some esoteric form of admiration, but rather a conviction that Fanon’s narration itself is both indicative and exemplary of a process of thinking that, for me, remains unparalleled in theorizing the role of the intellectual. Such a conviction requires us to read beyond the content of Wretched and be “reborn” in the Barthesian sense as readers. In essence, it is to simply follow the way Fanon himself allows us to actually trace how he dreams of “the native” or “the people” and thus accomplishes an affective leap, arguably, more completely than any other intellectual. This reading is, thus, an invitation to dream – even momentarily – of Fanon. (shrink)

International health-related research on human subjects entails unique ethical responsibilities and difficulties. Often, these difficulties are augmented by the lack of a local ethical review infrastructure. In a recent cross-national study conducted by us, three critical components of ethical regulation were identified—external oversight, local oversight and subject involvement—and integrated into the study design. These three concepts are outlined and established as an important aspect of ensuring ethical coherence in the local context, particularly when reviews by the local institutional review boards (...) cannot practically be obtained. The three levels of ethical oversight identified are suggested to be the framework within which future field studies on human subjects are developed and a standard for maintaining ethical rigorousness in research on humans. (shrink)

This study attempts to fill in two research gaps in the extant literature concerning the ecosystem for social innovation in the context of emerging market economies such as India. The study first attempts to assess the potential of corporate social responsibility (CSR) in not-for-profit entities such as technology business incubators (TBIs) to stimulate social innovations in the prevalent ecosystems in emerging markets. Further, using a random-effects Tobit model, the study examines the characteristics of firms that spend higher percentages of CSR (...) expenditure on not-for-profit TBIs/societies/trusts in India. The study provides policy suggestions to create an entrepreneurial ecosystem for promoting social innovation in emerging markets such as India. (shrink)

Pashmina is one of the most luxurious and finest fibres in the world. It is a special kind of wool obtained from Cashmere goats. Counterfeiting Pashmina is becoming a prevalent malpractice because of limited supply, expensive pricing and high demand in western markets. Presently, there is a lack of a low-cost and easily available approach for distinguishing authentic Pashmina apparels from other similar-looking products. Because of technological advances and cost reductions in digital image processing, we have been able to implement (...) a variety of image recognition systems on a practical level. In this study, we propose a deep learning model PashmNet for identification of Pashmina fabric using transfer learning. The technique proposed herein classifies Pashmina and non-Pashmina images accurately with classification accuracy of 97.4%. (shrink)

Contributed research papers on Indic philosophy.

Classical commentary on Nyāyasūtra of Gautama, aphoristic work on Nyaya philosophy.

The relatively simple central nervous system (CNS) of the Drosophila embryo provides a useful model system for investigating the mechanisms that generate and pattern complex nervous systems. Central to the generation of different types of neurons by precursor neuroblasts is the initial specification of neuroblast identity and the Drosophila segment polarity genes, genes that specify regions within a segment or repeating unit of the Drosophila embryo, have emerged recently as significant players in this process. During neurogenesis the segment polarity genes (...) are expressed in the neuroectodermal cells from which neuroblasts delaminate and they continue to be expressed in neuroblasts and their progeny. Loss-of-function mutations in these genes lead to a failure in the formation of neuroblasts and/or specification of neuroblast identity. Results from several recent studies suggest that regulatory interactions between segment polarity genes during neurogenesis lead to an increase in the number of neuroblasts and specification of different identities to neuroblasts within a population of cells. BioEssays 21:472–485, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

In this paper, we propose a general copula approach to accommodate non-normal continuous mixing distributions in multinomial probit models. In particular, we specify a multivariate mixing distribution that allows different marginal continuous parametric distributions for different coefficients. A new hybrid estimation technique is proposed to estimate the model, which combines the advantageous features of each of the maximum simulated likelihood inference technique and Bhat’s maximum approximate composite marginal likelihood inference approach. The effectiveness of our formulation and inference approach is (...) demonstrated through simulation exercises and an empirical application. (shrink)

The European Legacy, Volume 17, Issue 3, Page 400-401, June 2012.

The dissociation between statistical prediction and scientific explanation advanced by Bowers et al. for studies of vision using deep neural networks is also observed in several other domains of behavior research, and is in fact unavoidable when fitting large models such as deep nets and other supervised learners, with weak theoretical commitments, to restricted samples of highly stochastic behavioral phenomena.

Despite a growing focus on processes to promote gender equity, women remain significantly underrepresented in leadership positions in the Global South. In the present study we focus on the role of familial experiences in shaping and contesting gender ideologies of Pakistani women in the workplace. We specifically examine the reciprocal ways in which women leaders and their family members shape each other’s gender ideologies regarding the workplace. Data collected and analyzed for this study were semi-structured interviews with eight women in (...) positions of leadership in Lahore, Pakistan, and interviews with one family members of each of the women leaders. Using thematic narrative analysis, we identified three thematic phases: learning gender expectations, resistance, and familial transformation. These phases reflect the progression of developing, resisting, and influencing individual and familial gender ideologies. We document the manifestation of these phases in three specific domains: education, marriage and motherhood, and the workplace. We then discuss how these findings contribute to understanding the experiences of women leaders and perceptions of their family members regarding women’s role in the workplace. Findings from our research provide novel insights into the ways globalization and capitalism continue to shape the socio-cultural context for women leaders in the Global South. (shrink)

Animal personality refers to the consistency of variation in behavior among individuals which may be the driving force behind variations in complex behaviors as well. Individual personality could predict how well an organism would perform in behavior and cognition related tasks, as well as survive and thrive in its environment. Therefore, we would expect inter-individual variations in many behaviors, which would persist even if habituation to the experimental setup occurs, which generally results in convergence of behavior. Our study used wild-caught (...) zebrafish from three natural habitats with differing ecological regimes, to understand how consistency and repeatability in specific traits such as boldness, exploration, and spatial ability varies across and within populations even when habituation causes change in behavior. We found that the extent of individual variation differs between populations, with dynamic habitats showing similar repeatability. This indicates that habitat conditions are important drivers of individual variation in addition to other factors, such as sex or size of individuals within populations. Although we found that sex and size played an important role within some populations for some behaviors, in others, the variation was likely caused by other factors, for which we have not accounted. This study underlines the importance of studying inter-individual differences as the phenomenon that underpins multiple behavioral traits and explains the possible role of environmental and inherent factors that drive these differences. (shrink)