The little-known history of cleanliness and the forgotten pioneers of handwashing

Handwashing is a simple method for preventing the spread of pathogens. It is now common practice, but this was not always the case. Advocating for it often costed a doctor his career in the 1840s. Hospitals in the early 1800s had little idea of the significance of hygiene; thus, they were often mocked as disease-producing incubators or as "houses of death." Many of the ill and dying were kept on wards with no ventilation or access to clean water; hospitals were found to offer only the most basic care. The mortality rate for patients admitted to hospital was three to five times greater than that for individuals cared for at home. Doctors did not routinely wash their hands until the mid-1800s, and they would proceed straight from dissecting a corpse to delivering a baby, providing the basis for the spread of puerperal fever. Despite advances in modern medicine, healthcare providers still face the issue of infection outbreaks caused by patient care. While the body of scientific data supporting hand hygiene as the key strategy to prevent the spread of pathogens is substantial, we highlight that achieving this crucial, long-awaited breakthrough was a hard task through history.Peer reviewe

Parasite-Mediated Evolution of the Functional Part of the MHC in Primates

The major histocompatibility complex (MHC) is a key model of genetic polymorphism, but the mechanisms underlying its extreme variability are debated. Most hypotheses for MHC diversity focus on pathogen-driven selection and predict that MHC polymorphism evolves under the pressure of a diverse parasite fauna. Several studies reported that certain alleles offer protection against certain parasites, yet it remains unclear whether variation in parasite pressure more generally covaries with allelic diversity and rates of molecular evolution of MHC across species. We tested this prediction in a comparative study of 41 primate species. We characterized polymorphism of the exon 2 of DRB region of the MHC class II. Our phylogenetic analyses controlled for the potential effects of neutral mutation rate, population size, geographic origin and body mass and revealed that nematode species richness associates positively with nonsynonymous nucleotide substitution rate at the functional part of the molecule. We failed to find evidence for allelic diversity being strongly related to parasite species richness. Continental distribution was a strong predictor of both allelic diversity and substitution rate, with higher values in Malagasy and Neotropical primates. These results indicate that parasite pressure can influence the different estimates of MHC polymorphism, whereas geography plays an independent role in the natural history of MHC.Human Evolutionary Biolog

Effect of Ketamine on Dendritic Arbor Development and Survival of Immature GABAergic Neurons In Vitro

Ketamine, a noncompetitive antagonist of the N-methyl-D-aspartate type of glutamate receptors, was reported to induce neuronal cell death when administered to produce anesthesia in young rodents and monkeys. Subanesthetic doses of ketamine, as adjuvant to postoperative sedation and pain control, are also frequently administered to young children. However, the effects of these low concentrations of ketamine on neuronal development remain unknown. The present study was designed to evaluate the effects of increasing concentrations (0.01-40 μg/ml) and durations (1-96 h) of ketamine exposure on the differentiation and survival of immature γ-aminobutyric acidergic (GABAergic) interneurons in culture. In line with previous studies (Scallet et al., 2004), we found that a 1-h-long exposure to ketamine at concentrations ≥ 10 μg/ml was sufficient to trigger cell death. At lower concentrations of ketamine, cell loss was only observed when this drug was chronically (> 48 h) present in the culture medium. Most importantly, we found that a single episode of 4-h-long treatment with 5 μg/ml ketamine induced long-term alterations in dendritic growth, including a significant (p 24 h) of neurons to ketamine at concentrations as low as 0.01 μg/ml also severely impaired dendritic arbor development. These results suggest that, in addition to its dose-dependent ability to induce cell death, even very low concentrations of ketamine could interfere with dendritic arbor development of immature GABAergic neurons and thus could potentially interfere with the development neural network

THREE ESSAYS ON FIRM AND MANAGERIAL PERFORMANCE

The three essays of this dissertation examine managerial actions and strategies in response to firm-specific situations, and the resulting firm and managerial performance. Essay 1 disentangles managerial ability and firm efficiency and examines managerial ability conditional on firm efficiency. Prior research on managerial ability overlook under- lying firm efficiency. Observing that the two measures of quality are highly correlated, I disentangle managerial ability from firm efficiency and create new measures for innate (pure) managerial ability and relative managerial ability (conditional on firm efficiency). I categorize managers as underrated (high managerial ability, low firm efficiency), typical (managerial ability and firm efficiency at par), and overrated (low managerial ability, high firm efficiency), and examine the consequent corporate strategies, firm performance and CEO compensation. Overrated managers inherit (i.e., are in charge of) dynamic firms but adopt conservative strategies themselves; the opposite is true for underrated managers. Overrated managers elicit negative firm performance while underrated managers engender positive firm performance. In contrast, overrated managers are overcompensated and underrated man- agers are undercompensated; innate (pure) managerial ability, by itself, has no bearing upon compensation. These results indicate the importance of disentangling managerial ability from firm efficiency to better understand the relevance of corporate quality towards corporate strategies, firm performance and CEO compensation. It may be inferred that managerial ability, per se, is likely a hype. Essay 2 studies the impact of non-compete clause enforcement on firm performance and employees. Existing literature on non-compete clauses (NCCs) focuses on the effect on firm characteristics other than performance, and the effect on top executives rather than general employees. My research examines the effect of NCC enforcement on firm performance and general employees. For the full sample of firms NCC enforcement has a non-significant relation to firm financial performance, a positive, significant relation to firm operating performance, and a negative, significant relation to employee metrics (total employees, total employee expense and average wage). The results, however, change drastically for subsam- ples: firms with low versus high performance, and firms with weak versus strong policies. NCC enforcement has a positive (negative), significant relation to firm financial performance for firms with low (high) financial performance and a nonsignificant (negative) relation to firm financial performance for firms with weak (strong) corporate governance with mixed effects of NCC enforcement on operating performance. Taken together my findings provide initial evidence that NCC enforcement has a beneficial effect on the worst firms, a detrimental effect on the best firms, and a detrimental effect on employees overall. Essay 3 looks into the behavior of firm managers in response to success and distress. I examine prospect theory in the context of corporate decision making: how firm managers change corporate strategies in response to firm-specific success and firm-specific distress. Based on these changes in corporate strategies I categorize the behavioral disposition of managers as house money effect, status quo effect, conservatism effect, trying-to-break-even effect, status quo effect, and snake bite effect; and examine the subsequent firm performance of each group. Managers are more risk-avoiding if the intensity (duration) of success is higher (longer); managers are more risk-taking if the intensity (duration) of distress is higher (longer). Following success, house money effect managers have the smallest decrease in firm performance while conservative managers have the largest; following distress, trying-to- break-even managers have the largest increase in firm performance while snake bite effect managers had the largest decrease in firm performance. In addition, younger (smaller) firms are more risk-taking following distress (following success and distress) and firms with payout are more risk-avoiding following both success and distress. Younger (shorter tenured) CEO\u27s are also more risk-taking following distress (following success and distress) and female CEO\u27s are more risk-taking following distress. Overall, this paper provide supports for prospect theory in a corporate finance decision-making setting: firm managers have very different risk behaviors following gains (success) and distress (losses); and the risk attitude depends on the intensity and duration of success/distress. In addition, following either success or distress, risk-taking managers are rewarded with higher subsequent firm performance while risk-avoiding managers are punished with lower subsequent firm performance

VEGF is a chemoattractant for FGF-2–stimulated neural progenitors

Mmigration of undifferentiated neural progenitors is critical for the development and repair of the nervous system. However, the mechanisms and factors that regulate migration are not well understood. Here, we show that vascular endothelial growth factor (VEGF)-A, a major angiogenic factor, guides the directed migration of neural progenitors that do not display antigenic markers for neuron- or glia-restricted precursor cells. We demonstrate that progenitor cells express both VEGF receptor (VEGFR) 1 and VEGFR2, but signaling through VEGFR2 specifically mediates the chemotactic effect of VEGF. The expression of VEGFRs and the chemotaxis of progenitors in response to VEGF require the presence of fibroblast growth factor 2. These results demonstrate that VEGF is an attractive guidance cue for the migration of undifferentiated neural progenitors and offer a mechanistic link between neurogenesis and angiogenesis in the nervous system

Reversal of age-related learning deficiency by the vertebrate PACAP and IGF-1 in a novel invertebrate model of aging: the pond snail (Lymnaea Stagnalis)

With the increase of life span, nonpathological age-related memory decline is affecting an increasing number of people. However, there is evidence that age-associated memory impairment only suspends, rather than irreversibly extinguishes, the intrinsic capacity of the aging nervous system for plasticity (1). Here, using a molluscan model system, we show that the age-related decline in memory performance can be reversed by administration of the pituitary adenylate cyclase activating polypeptide (PACAP). Our earlier findings showed that a homolog of the vertebrate PACAP38 and its receptors exist in the pond snail (Lymnaea stagnalis) brain (2), and it is both necessary and instructive for memory formation after reward conditioning in young animals (3). Here we show that exogenous PACAP38 boosts memory formation in aged Lymnaea, where endogenous PACAP38 levels are low in the brain. Treatment with insulin-like growth factor-1, which in vertebrates was shown to transactivate PACAP type I (PAC1) receptors (4) also boosts memory formation in aged pond snails. Due to the evolutionarily conserved nature of these polypeptides and their established role in memory and synaptic plasticity, there is a very high probability that they could also act as “memory rejuvenating” agents in humans

Hadron calorimeter with MAPD readout in the NA61/SHINE experiment

The modular hadron calorimeter with micro-pixel avalanche photodiodes readout for the NA61/SHINE experiment at the CERN SPS is presented. The calorimeter consists of 44 independent modules with lead-scintillator sandwich structure. The light from the scintillator tiles is captured by and transported with WLS-fibers embedded in scintillator grooves. The construction provides a longitudinal segmentation of the module in 10 sections with independent MAPD readout. MAPDs with pixel density of $~10^{4}$/mm$^2$ ensure good linearity of calorimeter response in a wide dynamical range. The performance of the calorimeter prototype in a beam test is reported

Early Postnatal Migration and Development of Layer II Pyramidal Neurons in the Rodent Cingulate/Retrosplenial Cortex

The cingulate and retrosplenial regions are major components of the dorsomedial (dm) limbic cortex and have been implicated in a range of cognitive functions such as emotion, attention, and spatial memory. While the structure and connectivity of these cortices are well characterized, little is known about their development. Notably, the timing and mode of migration that govern the appropriate positioning of late-born neurons remain unknown. Here, we analyzed migratory events during the early postnatal period from ventricular/subventricular zone (VZ/SVZ) to the cerebral cortex by transducing neuronal precursors in the VZ/SVZ of newborn rats/mice with Tomato/green fluorescent protein-encoding lentivectors. We have identified a pool of postmitotic pyramidal precursors in the dm part of the neonatal VZ/SVZ that migrate into the medial limbic cortex during the first postnatal week. Time-lapse imaging demonstrates that these cells migrate on radial glial fibers by locomotion and display morphological and behavioral changes as they travel through the white matter and enter into the cortical gray matter. In the granular retrosplenial cortex, these cells give rise to a Satb2+ pyramidal subtype and develop dendritic bundles in layer I. Our observations provide the first insight into the patterns and dynamics of cell migration into the medial limbic corte