The commodification of health care in Kerala, South India: science, consumerism and markets

In India, alongside Information Technology, health care has become a leading sector in the country‘s development as a 'knowledge economy' (World Bank 2005). One of the major achievements and beacons of economic reform is the growth of some of the most technologically advanced hospitals in the world. This thesis examines the social processes shaping the expansion of the private health care system in the state of Kerala, South India, where large corporate hospitals and 'super-speciality' medicine have spread throughout urban and many rural areas. It explores the intersections between the local and the global, as the health system becomes the major driver of industrial development, unevenly linking the local health care system to the global marketplace for technologies, health care professionals and patients. It examines the three faces of the health care system in Kerala - as a knowledge industry and route to social mobility for the middle classes, in particular doctors and nurses; secondly, as a consumer economy, as people prioritise spending on health care and shop for treatment in the urban marketplace; and finally as a moral economy, as people develop high levels of dependency on doctors, hospitals and technologies in the hope of receiving good health care. The ethnography is set in Malabar, Northern Kerala, where the expansion of private health care has been financed by remittances from migration to the Arabian Gulf countries. The thesis examines the influence of migration and economic reforms on local ecologies of health and health care; the impact of the globalisation of trade in health services in the developing world; the relationship between the private health care system and the middle classes in South Asia; and the role of markets in the delivery of health services. Based on 18 months of participant observation across the urban and rural health care market with local communities of doctors and patients, it examines how doctors and patients adjust to a changing ecology and economy of health care

Distribution of Allatostatin C-like Immunoreactivity in the Central Nervous System of the Copepod Crustacean \u3cem\u3eCalanus finmarchicus\u3c/em\u3e

The C-type allatostatins (C-ASTs) are a family of highly pleiotropic arthropod neuropeptides. In crustaceans, transcriptomic/mass spectral studies have identified C-ASTs in the nervous systems of many species; the cellular distributions of these peptides remain unknown. Here, the distribution of C-AST was mapped in the nervous system of the copepod Calanus finmarchicus, the major contributor to the North Atlantic’s zooplanktonic biomass; C-AST-immunopositive neurons were identified in the protocerebrum, in several peripheral ganglia associated with feeding appendages, and in the ganglia controlling the swimming legs, with immunopositive axons present throughout the ventral nerve cord. In addition, axons innervating the dorsal longitudinal and ventral longitudinal muscles of the body wall of the metasome were labeled by the C-AST antibody. While the distribution of C-AST-like immunoreactivity was similar between sexes, several differences were noted, i.e., two pair of somata located at the deutocerebral/tritocerebral border in males and immunopositive fibers that surround the genital opening in females. To place the C-AST-like labeling into context with those of several previously mapped peptides, i.e., A-type allatostatin (A-AST) and tachykinin-related peptide (TRP), we conducted double-labeling studies; the C-AST-like immunopositive neurons appear distinct from those expressing either A-AST or TRP (and through extrapolation, pigment dispersing hormone). Collectively, our data represent the first mapping of C-AST in crustacean neural tissue, show that sex-specific differences in the distribution of C-AST exist in the C. finmarchicus CNS, and suggest that the peptide may be involved in the modulation of both feeding and postural control/locomotion

Inhibition of Nitric Oxide and Soluble Guanylyl Cyclase Signaling Affects Olfactory Neuron Activity in the Moth, \u3cem\u3eManduca sexta\u3c/em\u3e

Nitric oxide is emerging as an important modulator of many physiological processes including olfaction, yet the function of this gas in the processing of olfactory information remains poorly understood. In the antennal lobe of the moth, Manduca sexta, nitric oxide is produced in response to odor stimulation, and many interneurons express soluble guanylyl cyclase, a well-characterized nitric oxide target. We used intracellular recording and staining coupled with pharmacological manipulation of nitric oxide and soluble guanylyl cyclase to test the hypothesis that nitric oxide modulates odor responsiveness in olfactory interneurons through soluble guanylyl cyclase-dependent pathways. Nitric oxide synthase inhibition resulted in pronounced effects on the resting level of firing and the responses to odor stimulation in most interneurons. Effects ranged from bursting to strong attenuation of activity and were often accompanied by membrane depolarization coupled with a change in input resistance. Blocking nitric oxide activation of soluble guanylyl cyclase signaling mimicked the effects of nitric oxide synthase inhibitors in a subset of olfactory neurons, while other cells were differentially affected by this treatment. Together, these results suggest that nitric oxide is required for proper olfactory function, and likely acts through soluble guanylyl cyclase-dependent and -independent mechanisms in different subsets of neurons

Spiking Patterns and Their Functional Implications in the Antennal Lobe of the Tobacco Hornworm \u3cem\u3eManduca sexta\u3c/em\u3e

Bursting as well as tonic firing patterns have been described in various sensory systems. In the olfactory system, spontaneous bursts have been observed in neurons distributed across several synaptic levels, from the periphery, to the olfactory bulb (OB) and to the olfactory cortex. Several in vitro studies indicate that spontaneous firing patterns may be viewed as “fingerprints” of different types of neurons that exhibit distinct functions in the OB. It is still not known, however, if and how neuronal burstiness is correlated with the coding of natural olfactory stimuli. We thus conducted an in vivo study to probe this question in the OB equivalent structure of insects, the antennal lobe (AL) of the tobacco hornworm Manduca sexta. We found that in the moth\u27s AL, both projection (output) neurons (PNs) and local interneurons (LNs) are spontaneously active, but PNs tend to produce spike bursts while LNs fire more regularly. In addition, we found that the burstiness of PNs is correlated with the strength of their responses to odor stimulation – the more bursting the stronger their responses to odors. Moreover, the burstiness of PNs was also positively correlated with the spontaneous firing rate of these neurons, and pharmacological reduction of bursting resulted in a decrease of the neurons\u27 responsiveness. These results suggest that neuronal burstiness reflects a physiological state of these neurons that is directly linked to their response characteristics

Prioritization of Kidney Cell Types Highlights Myofibroblast Cells in Regulating Human Blood Pressure

INTRODUCTION: Blood pressure (BP) is a highly heritable trait with over 2000 underlying genomic loci identified to date. Although the kidney plays a key role, little is known about specific cell types involved in the genetic regulation of BP.METHODS: Here, we applied stratified linkage disequilibrium score (LDSC) regression to connect BP genome-wide association studies (GWAS) results to specific cell types of the mature human kidney. We used the largest single-stage BP genome-wide analysis to date, including up to 1,028,980 adults of European ancestry, and single-cell transcriptomic data from 14 mature human kidneys, with mean age of 41 years.RESULTS: Our analyses prioritized myofibroblasts and endothelial cells, among the total of 33 annotated cell type, as specifically involved in BP regulation (P &lt; 0.05/33, i.e., 0.001515). Enrichment of heritability for systolic BP (SBP) was observed in myofibroblast cells in mature human kidney cortex, and enrichment of heritability for diastolic BP (DBP) was observed in descending vasa recta and peritubular capillary endothelial cells as well as stromal myofibroblast cells. The new finding of myofibroblast, the significant cell type for both BP traits, was consistent in 8 replication efforts using 7 sets of independent data, including in human fetal kidney, in East-Asian (EAS) ancestry, using mouse single-cell RNA sequencing (scRNA-seq) data, and when using another prioritization method.CONCLUSION: Our findings provide a solid basis for follow-up studies to further identify genes and mechanisms in myofibroblast cells that underlie the regulation of BP.</p

Training recruiters to randomized trials to facilitate recruitment and informed consent by exploring patients' treatment preferences

BACKGROUND: Patients’ treatment preferences are often cited as barriers to recruitment in randomized controlled trials (RCTs). We investigated how RCT recruiters reacted to patients’ treatment preferences and identified key strategies to improve informed decision-making and trial recruitment. METHODS: Audio-recordings of 103 RCT recruitment appointments with 96 participants in three UK multicenter pragmatic RCTs were analyzed using content and thematic analysis. Recruiters’ responses to expressed treatment preferences were assessed in one RCT (ProtecT - Prostate testing for cancer and Treatment) in which training on exploring preferences had been given, and compared with two other RCTs where this specific training had not been given. RESULTS: Recruiters elicited treatment preferences similarly in all RCTs but responses to expressed preferences differed substantially. In the ProtecT RCT, patients’ preferences were not accepted at face value but were explored and discussed at length in three key ways: eliciting and acknowledging the preference rationale, balancing treatment views, and emphasizing the need to keep an open mind and consider all treatments. By exploring preferences, recruiters enabled participants to become clearer about whether their views were robust enough to be sustained or were sufficiently weak that participation in the RCT became possible. Conversely, in the other RCTs, treatment preferences were often readily accepted without further discussion or understanding the reasoning behind them, suggesting that patients were not given the opportunity to fully consider all treatments and trial participation. CONCLUSIONS: Recruiters can be trained to elicit and address patients’ treatment preferences, enabling those who may not have considered trial participation to do so. Without specific guidance, some RCT recruiters are likely to accept initial preferences at face value, missing opportunities to promote more informed decision-making. Training interventions for recruiters that incorporate key strategies to manage treatment preferences, as in the ProtecT study, are required to facilitate recruitment and informed consent. TRIAL REGISTRATION: ProtecT RCT: Current Controlled Trials ISRCTN20141297. The other two trials are registered but have asked to be anonymized

The Ursinus Weekly, January 15, 1962

Shadowy figure of Ursinus\u27 past publishes volume of 66 poems • Dr. Snyder, Forum speaker, outlines seven strong forces in Africa today • Spontaneous fun object of new social committee • Prof casts critical eye over Lantern; Discovers sound creative instincts • Bursting water pipe sends Alumni Office to 620 Main • Student teachers\u27 light-hearted talk explains what\u27s not in the Ed. book • Best-dressed co-ed sought by Weekly • Shares of the pecuniary pie • Pre-medders hear about corneal transplant work • Editorial: Appeal of wrestling • Ursinus in the past • Letters to the editor • Obituary for a timid intellectual • Dryfoos sets two Ursinus cage marks; Dean ties record with quick pin • Pair of heartbreaking losses catch grapplers last week • Basketball begins • Frymen flounder; Lose to PMC, 92-80; Drop thriller to Swarthmore, 89 to 85 • Greek gleaningshttps://digitalcommons.ursinus.edu/weekly/1309/thumbnail.jp

Resistance to Cancer Treatment: The Role of Somatic Genetic Events and the Challenges for Targeted Therapies

Therapeutic resistance remains a major cause of cancer-related deaths. Resistance can occur from the outset of treatment or as an acquired phenomenon after an initial clinical response. Therapeutic resistance is an almost universal phenomenon in the treatment of metastatic cancers. The advent of molecularly targeted treatments brought greater efficacy in patients whose tumors express a particular target or molecular signature. However, resistance remains a predictable challenge. This article provides an overview of somatic genomic events that confer resistance to cancer therapies. Some examples, including BCR–Abl, EML4–ALK, and the androgen receptor, contain mutations in the target itself, which hamper binding and inhibitory functions of therapeutic agents. There are also examples of somatic genetic changes in other genes or pathways that result in resistance by circumventing the inhibitor, as in resistance to trastuzumab and BRAF inhibitors. Yet other examples results in activation of cytoprotective genes. The fact that all of these mechanisms of resistance are due to somatic changes in the tumor’s genome makes targeting them selectively a feasible goal. To identify and validate these changes, it is important to obtain biopsies of clinically resistant tumors. A rational consequence of this evolving knowledge is the growing appreciation that combinations of inhibitors will be needed to anticipate and overcome therapeutic resistance

A record of Neogene seawater δ11B reconstructed from paired δ11B analyses on benthic and planktic foraminifera

The work was supported by NERC grants NE/I006176/1 (Gavin L. Foster and Caroline H. Lear), NE/H006273/1 (Gavin L. Foster), NE/I006168/1 and NE/K014137/1 and a Royal Society Research Merit Award (Paul A. Wilson), a NERC Independent Research Fellowship NE/K00901X/1 (Mathis P. Hain) and a NERC studentship (Rosanna Greenop).The boron isotope composition (δ11B) of foraminiferal calcite reflects the pH and the boron isotope composition of the seawater the foraminifer grew in. For pH reconstructions, the δ11B of seawater must therefore be known, but information on this parameter is limited. Here we reconstruct Neogene seawater δ11B based on the δ11B difference between paired measurements of planktic and benthic foraminifera and an estimate of the coeval water column pH gradient from their δ13C values. Carbon cycle model simulations underscore that the ΔpH-Δδ13C relationship is relatively insensitive to ocean and carbon cycle changes, validating our approach. Our reconstructions suggest that δ11Bsw was ∼37.5‰ during the early and middle Miocene (roughly 23-12 Ma) and rapidly increased during the late Miocene (between 12 and 5 Ma) towards the modern value of 39.61 ‰. Strikingly, this pattern is similar to the evolution of the seawater isotope composition of Mg, Li and Ca, suggesting a common forcing mechanism. Based on the observed direction of change, we hypothesize that an increase in secondary mineral formation during continental weathering affected the isotope composition of riverine input to the ocean since 14 Ma.Publisher PDFPeer reviewe

Optimising recruitment and informed consent in randomised controlled trials:the development and implementation of the QuinteT Recruitment Intervention (QRI)

BACKGROUND: Pragmatic randomised controlled trials (RCTs) are considered essential to determine effective interventions for routine clinical practice, but many fail to recruit participants efficiently, and some really important RCTs are not undertaken because recruitment is thought to be too difficult. The ‘QuinteT Recruitment Intervention’ (QRI) aims to facilitate informed decision making by patients about RCT participation and to increase recruitment. This paper presents the development and implementation of the QRI. METHODS: The QRI developed iteratively as a complex intervention. It emerged from the National Institute for Health Research (NIHR) ProtecT trial and has been developed further in 13 RCTs. The final version of the QRI uses a combination of standard and innovative qualitative research methods with some simple quantification to understand recruitment and identify sources of difficulties. RESULTS: The QRI has two major phases: understanding recruitment as it happens and then developing a plan of action to address identified difficulties and optimise informed consent in collaboration with the RCT chief investigator (CI) and the Clinical Trials Unit (CTU). The plan of action usually includes RCT-specific, as well as generic, aspects. The QRI can be used in two ways: it can be integrated into the feasibility/pilot or main phase of an RCT to prevent difficulties developing and optimise recruitment from the start, or it can be applied to an ongoing RCT experiencing recruitment shortfalls, with a view to rapidly improving recruitment and informed consent or gathering evidence to justify RCT closure. CONCLUSIONS: The QRI provides a flexible way of understanding recruitment difficulties and producing a plan to address them while ensuring engaged and well-informed decision making by patients. It can facilitate recruitment to the most controversial and important RCTs. QRIs are likely to be of interest to the CIs and CTUs developing proposals for ‘difficult’ RCTs or for RCTs with lower than expected recruitment and to the funding bodies wishing to promote efficient recruitment in pragmatic RCTs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1391-4) contains supplementary material, which is available to authorized users