Where constructionism and critical realism converge: interrogating the domain of epistemological relativism

The paper interrogates the status, nature and significance of epistemological relativism as a key element of constructionism and critical realism. It finds that epistemological relativism is espoused by authorities in critical realism and marginalized or displaced in the field of management and organization studies, resulting in forms of analysis that are empirically, but not fully critically, realist. This evaluation prompts reflection on the question of whether, how and with what implications epistemological relativism might be recast at the heart of critical realist studies of management and organization

Rotation of planet-harbouring stars

The rotation rate of a star has important implications for the detectability, characterisation and stability of any planets that may be orbiting it. This chapter gives a brief overview of stellar rotation before describing the methods used to measure the rotation periods of planet host stars, the factors affecting the evolution of a star's rotation rate, stellar age estimates based on rotation, and an overview of the observed trends in the rotation properties of stars with planets.Comment: 16 pages, 4 figures: Invited review to appear in 'Handbook of Exoplanets', Springer Reference Works, edited by Hans J. Deeg and Juan Antonio Belmont

Improving validity of informed consent for biomedical research in Zambia using a laboratory exposure intervention.

BACKGROUND: Complex biomedical research can lead to disquiet in communities with limited exposure to scientific discussions, leading to rumours or to high drop-out rates. We set out to test an intervention designed to address apprehensions commonly encountered in a community where literacy is uncommon, and where complex biomedical research has been conducted for over a decade. We aimed to determine if it could improve the validity of consent. METHODS: Data were collected using focus group discussions, key informant interviews and observations. We designed an intervention that exposed participants to a detailed demonstration of laboratory processes. Each group was interviewed twice in a day, before and after exposure to the intervention in order to assess changes in their views. RESULTS: Factors that motivated people to participate in invasive biomedical research included a desire to stay healthy because of the screening during the recruitment process, regular advice from doctors, free medical services, and trust in the researchers. Inhibiting factors were limited knowledge about samples taken from their bodies during endoscopic procedures, the impact of endoscopy on the function of internal organs, and concerns about the use of biomedical samples. The belief that blood can be used for Satanic practices also created insecurities about drawing of blood samples. Further inhibiting factors included a fear of being labelled as HIV positive if known to consult heath workers repeatedly, and gender inequality. Concerns about the use and storage of blood and tissue samples were overcome by a laboratory exposure intervention. CONCLUSION: Selecting a group of members from target community and engaging them in a laboratory exposure intervention could be a useful tool for enhancing specific aspects of consent for biomedical research. Further work is needed to determine the extent to which improved understanding permeates beyond the immediate group participating in the intervention

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

Membrane Docking Geometry of GRP1 PH Domain Bound to a Target Lipid Bilayer: An EPR Site-Directed Spin-Labeling and Relaxation Study

The second messenger lipid PIP3 (phosphatidylinositol-3,4,5-trisphosphate) is generated by the lipid kinase PI3K (phosphoinositide-3-kinase) in the inner leaflet of the plasma membrane, where it regulates a broad array of cell processes by recruiting multiple signaling proteins containing PIP3-specific pleckstrin homology (PH) domains to the membrane surface. Despite the broad importance of PIP3-specific PH domains, the membrane docking geometry of a PH domain bound to its target PIP3 lipid on a bilayer surface has not yet been experimentally determined. The present study employs EPR site-directed spin labeling and relaxation methods to elucidate the membrane docking geometry of GRP1 PH domain bound to bilayer-embedded PIP3. The model target bilayer contains the neutral background lipid PC and both essential targeting lipids: (i) PIP3 target lipid that provides specificity and affinity, and (ii) PS facilitator lipid that enhances the PIP3 on-rate via an electrostatic search mechanism. The EPR approach measures membrane depth parameters for 18 function-retaining spin labels coupled to the PH domain, and for calibration spin labels coupled to phospholipids. The resulting depth parameters, together with the known high resolution structure of the co-complex between GRP1 PH domain and the PIP3 headgroup, provide sufficient constraints to define an optimized, self-consistent membrane docking geometry. In this optimized geometry the PH domain engulfs the PIP3 headgroup with minimal bilayer penetration, yielding the shallowest membrane position yet described for a lipid binding domain. This binding interaction displaces the PIP3 headgroup from its lowest energy position and orientation in the bilayer, but the headgroup remains within its energetically accessible depth and angular ranges. Finally, the optimized docking geometry explains previous biophysical findings including mutations observed to disrupt membrane binding, and the rapid lateral diffusion observed for PIP3-bound GRP1 PH domain on supported lipid bilayers

A high-precision near-infrared survey for radial velocity variable low-mass stars using CSHELL and a methane gas cell

We present the results of a precise near-infrared (NIR) radial velocity (RV) survey of 32 low-mass stars with spectral types K2-M4 using CSHELL at the NASA InfraRed Telescope Facility in the K band with an isotopologue methane gas cell to achieve wavelength calibration and a novel, iterative RV extraction method. We surveyed 14 members of young (≈25-150 Myr) moving groups, the young field star ϵ Eridani, and 18 nearby (<25 pc) low-mass stars and achieved typical single-measurement precisions of 8-15 m s-1with a long-term stability of 15-50 m s-1 over longer baselines. We obtain the best NIR RV constraints to date on 27 targets in our sample, 19 of which were never followed by high-precision RV surveys. Our results indicate that very active stars can display long-term RV variations as low as ∼25-50 m s-1 at ≈2.3125 μm, thus constraining the effect of jitter at these wavelengths. We provide the first multiwavelength confirmation of GJ 876 bc and independently retrieve orbital parameters consistent with previous studies. We recovered RV variabilities for HD 160934 AB and GJ 725 AB that are consistent with their known binary orbits, and nine other targets are candidate RV variables with a statistical significance of 3σ-5σ. Our method, combined with the new iSHELL spectrograph, will yield long-term RV precisions of ≲5 m s-1 in the NIR, which will allow the detection of super-Earths near the habitable zone of mid-M dwarfs

Population-Based Incidence of Typhoid Fever in an Urban Informal Settlement and a Rural Area in Kenya: Implications for Typhoid Vaccine Use in Africa

Background: High rates of typhoid fever in children in urban settings in Asia have led to focus on childhood immunization in Asian cities, but not in Africa, where data, mostly from rural areas, have shown low disease incidence. We set out to compare incidence of typhoid fever in a densely populated urban slum and a rural community in Kenya, hypothesizing higher rates in the urban area, given crowding and suboptimal access to safe water, sanitation and hygiene. Methods: During 2007-9, we conducted population-based surveillance in Kibera, an urban informal settlement in Nairobi, and in Lwak, a rural area in western Kenya. Participants had free access to study clinics; field workers visited their homes biweekly to collect information about acute illnesses. In clinic, blood cultures were processed from patients with fever or pneumonia. Crude and adjusted incidence rates were calculated. Results: In the urban site, the overall crude incidence of Salmonella enterica serovar Typhi (S. Typhi) bacteremia was 247 cases per 100,000 person-years of observation (pyo) with highest rates in children 5–9 years old (596 per 100,000 pyo) and 2–4 years old (521 per 100,000 pyo). Crude overall incidence in Lwak was 29 cases per 100,000 pyo with low rates in children 2–4 and 5–9 years old (28 and 18 cases per 100,000 pyo, respectively). Adjusted incidence rates were highest in 2–4 year old urban children (2,243 per 100,000 pyo) which were.15-fold higher than rates in the rural site for the same age group

Erythrocyte Transketolase Activity, Markers of Cardiac Dysfunction and the Diagnosis of Infantile Beriberi

Infantile beriberi, or clinical thiamin (vitamin B1) deficiency in infants, is a forgotten disease in Asia, where ∼100 years ago it was a major public health problem. Children aged ∼2–3 months present in cardiac failure but usually rapidly improve if given thiamin injections. It remains relatively common in Vientiane, Lao PDR (Laos) probably because of prolonged intra- and post-partum maternal food avoidance behaviours. There has been very little recent research on the best diagnostic techniques. We conducted a case control study of 47 infants with beriberi and age-matched afebrile and febrile controls in Vientiane. The conventional measures of thiamin deficiency, basal and activated erythrocyte transketolase activities (ETK) and activation (α) coefficients, were assayed along with three markers of cardiac dysfunction - plasma brain natriuretic peptide, N-terminal pro-brain natriuretic peptide, and troponin T. Basal ETK was a better biochemical marker of infantile beriberi than the activation coefficient. Raised plasma troponin T may be a useful indicator of infantile beriberi in babies at risk and in the absence of other evident causes

Subsequent Event Risk in Individuals with Established Coronary Heart Disease:Design and Rationale of the GENIUS-CHD Consortium

BACKGROUND: The "GENetIcs of sUbSequent Coronary Heart Disease" (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185,614 participants with either acute coronary syndrome, stable CHD or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. RESULTS: Enrollment into the individual studies took place between 1985 to present day with duration of follow up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (HR 1.15 95% CI 1.14-1.16) per 5-year increase, male sex (HR 1.17, 95% CI 1.13-1.21) and smoking (HR 1.43, 95% CI 1.35-1.51) with risk of subsequent CHD death or myocardial infarction, and differing associations with other individual and composite cardiovascular endpoints. CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and non-genetic determinants of subsequent event risk in individuals with established CHD, in order to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators

Measurement of the W-pair cross section in e+e−e^+ e^- collisions at 172 GeV

The e+e- --> W+W- cross section is measured in a data sample collected by ALEPH at a mean centre--of--mass energy of 172.09 GEV, corresponding to an integrated luminosity of 10.65 pb-1. Cross sections are given for the three topologies, fully leptonic, semi-leptonic and hadronic of a W-pair decay. Under the assumption that no other decay modes are present, the W-pair cross section is measured to be 11.7 +- 1.2 (stat.) +- 0.3 (syst.) pb. The existence of the triple gauge boson vertex of the Standard Model is clearly preferred by the data. The decay branching ratio of the W boson into hadrons is measured to be B(W --> hadrons) = 67.7 +- 3.1 (stat.) +- 0.7 (syst.)%, allowing a determination of the CKM matrix element |Vcs|= 0.98 +- 0.14 (stat.) +- 0.03 (syst.)