Growth patterns in early childhood: Better trajectories in Afro-Ecuadorians independent of sex and socioeconomic factors.

The first years of life are the most dynamic period for childhood growth. There are limited data available on growth patterns of infants and children living in rural Latin America. The aim of this study was to describe the growth patterns from birth to 5years in children living in a rural District of tropical coastal Ecuador using data from a birth cohort of 2404 neonates. We hypothesize that there would be growth differences according to ethnicity and sex. Evaluations were conducted at birth or until 2weeks of age and at 7, 13, 24, 36 and 60months during clinic and home visits. Individual growth trajectories for weight-for-age, height-for-age and weight/height-for-age Z-scores were estimated using multilevel models. Girls were lighter and shorter than boys at birth. However, Afro-Ecuadorian children (versus mestizo or indigenous) were longer/taller and heavier throughout the first 5years of life and had greater mean trajectories for HAZ and WAZ independent of sex and socioeconomic factors. Our data indicate that ethnicity is a determinant of growth trajectories during the first 5years of life independent of socioeconomic factors in a birth cohort conducted in a rural region of Latin America

Determinants of career aspirations of medical students in southern China

<p>Abstract</p> <p>Background</p> <p>With recent changes in both the Chinese medical system and compensation of medical doctors, the career aspirations of Chinese medical students have become more diverse. Shantou University Medical College has conducted evaluations and instituted programs to enhance student preparedness to enter a variety of medical careers.</p> <p>Methods</p> <p>A survey was conducted with 85 students to evaluate medical career aspirations and their association with family background, personal skills, English language proficiency, and interest in biomedical research, which were considered as possible factors affecting their career interest.</p> <p>Results</p> <p>Chinese students aspire to traditional as well as nontraditional medical careers. A significant minority of students are now interested in nontraditional careers such as medical teaching or research. However, poor proficiency in the English language and lack of computer skills may limit their academic and career opportunities.</p> <p>Conclusion</p> <p>Career aspirations have changed among medical undergraduates. Although many wish to pursue a traditional clinical doctor career, many are interested in research and teaching careers. Factors such as family background, personal characteristics, school mentoring, and extracurricular support may play a role.</p

Consistent improvement in health-related quality of life with tiotropium in patients with chronic obstructive pulmonary disease: Novel and conventional responder analyses.

INTRODUCTION: Improving health-related quality of life (HRQoL) in COPD patients is an important pharmacotherapeutic objective. This study investigated the extent, consistency, and durability of tiotropium maintenance therapy impact on HRQoL in moderate-to-very severe COPD. METHODS: Patients received once-daily tiotropium 18 μg (n = 5244) or placebo (n = 4799) via HandiHaler(®) (10 trials), or once-daily tiotropium 5 μg (n = 2622) or placebo (n = 2618) via Respimat(®) inhaler (3 trials). St George's Respiratory Questionnaire (SGRQ) total scores were measured at baseline, and 6 months (13 trials) and 1 year (9 trials) from treatment start. Adjusted mean differences between treatments for change from baseline in total scores were calculated at each time-point for each trial. Responder and deteriorator rates (decrease or increase in score ≥4 units from baseline, respectively), net benefit (responder rate increase plus deteriorator rate decrease), and cumulative improvement and deterioration were determined. RESULTS: Adjusted mean total score differences between treatments for change from baseline were significant (p < 0.05) in favor of tiotropium in 10/13 trials at 6 months and in 8/9 trials at 1 year. In all trials, estimated differences in responder rates between treatments favored tiotropium (significant [p < 0.05]: 5/13 trials at 6 months; 8/9 trials at 1 year). Net benefit favored tiotropium and cumulative improvement rates were consistently greater and deterioration rates consistently lower for tiotropium versus placebo. CONCLUSIONS: Tiotropium maintenance therapy significantly and consistently improved HRQoL in moderate-to-very severe COPD patients in a durable manner. These results may provide a benchmark for assessing benefits on HRQoL of other COPD treatments

Phase I study of pegylated liposomal doxorubicin and the multidrug-resistance modulator, valspodar

Valspodar, a P-glycoprotein modulator, affects pharmacokinetics of doxorubicin when administered in combination, resulting in doxorubicin dose reduction. In animal models, valspodar has minimal interaction with pegylated liposomal doxorubicin (PEG-LD). To determine any pharmacokinetic interaction in humans, we designed a study to determine maximum tolerated dose, dose-limiting toxicity (DLT), and pharmacokinetics of total doxorubicin, in PEG-LD and valspodar combination therapy in patients with advanced malignancies. Patients received PEG-LD 20–25 mg m−2 intravenously over 1 h for cycle one. In subsequent 2-week cycles, valspodar was administered as 72 h continuous intravenous infusion with PEG-LD beginning at 8 mg m−2 and escalated in an accelerated titration design to 25 mg m−2. Pharmacokinetic data were collected with and without valspodar. A total of 14 patients completed at least two cycles of therapy. No DLTs were observed in six patients treated at the highest level of PEG-LD 25 mg m−2. The most common toxicities were fatigue, nausea, vomiting, mucositis, palmar plantar erythrodysesthesia, diarrhoea, and ataxia. Partial responses were observed in patients with breast and ovarian carcinoma. The mean (range) total doxorubicin clearance decreased from 27 (10–73) ml h−1 m−2 in cycle 1 to 18 (3–37) ml h−1 m−2 with the addition of valspodar in cycle 2 (P=0.009). Treatment with PEG-LD 25 mg m−2 in combination with valspodar results in a moderate prolongation of total doxorubicin clearance and half-life but did not increase the toxicity of this agent

Species-specific responses of Late Quaternary megafauna to climate and humans

Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary remain contentious. We use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, underscoring the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change.This paper is in the memory of our friend and colleague Dr. Andrei Sher, who was a major contributor of this study. Dr Sher died unexpectedly, but his major contributions to the field of Quaternary science will be remembered and appreciated for many years to come. We are grateful to Dr. Adrian Lister and Dr. Tony Stuart for guides and discussions. Thanks to Tina B. Brandt, Dr. Bryan Hockett and Alice Telka for laboratory help and samples and to L. Malik R. Thrane for his work on the megafauna locality database. Data taken from the Stage 3 project was partly funded by Grant #F/757/A from the Leverhulme Trust, together with a grant from the McDonald Grants and Awards Fund. We acknowledge the Danish National Research Foundation, the Lundbeck Foundation, the Danish Council for Independent Research and the US National Science Foundation for financial suppor

Dark Energy Survey Year 3 results: Constraints on extensions to ΛcDM with weak lensing and galaxy clustering

We constrain six possible extensions to the Λ cold dark matter (CDM) model using measurements from the Dark Energy Survey's first three years of observations, alone and in combination with external cosmological probes. The DES data are the two-point correlation functions of weak gravitational lensing, galaxy clustering, and their cross-correlation. We use simulated data vectors and blind analyses of real data to validate the robustness of our results to astrophysical and modeling systematic errors. In many cases, constraining power is limited by the absence of theoretical predictions beyond the linear regime that are reliable at our required precision. The ΛCDM extensions are dark energy with a time-dependent equation of state, nonzero spatial curvature, additional relativistic degrees of freedom, sterile neutrinos with eV-scale mass, modifications of gravitational physics, and a binned σ8(z) model which serves as a phenomenological probe of structure growth. For the time-varying dark energy equation of state evaluated at the pivot redshift we find (wp,wa)=(-0.99-0.17+0.28,-0.9±1.2) at 68% confidence with zp=0.24 from the DES measurements alone, and (wp,wa)=(-1.03-0.03+0.04,-0.4-0.3+0.4) with zp=0.21 for the combination of all data considered. Curvature constraints of ωk=0.0009±0.0017 and effective relativistic species Neff=3.10-0.16+0.15 are dominated by external data, though adding DES information to external low-redshift probes tightens the ωk constraints that can be made without cosmic microwave background observables by 20%. For massive sterile neutrinos, DES combined with external data improves the upper bound on the mass meff by a factor of 3 compared to previous analyses, giving 95% limits of (ΔNeff,meff)≤(0.28,0.20 eV) when using priors matching a comparable Planck analysis. For modified gravity, we constrain changes to the lensing and Poisson equations controlled by functions ς(k,z)=ς0ωΛ(z)/ωΛ,0 and μ(k,z)=μ0ωΛ(z)/ωΛ,0, respectively, to ς0=0.6-0.5+0.4 from DES alone and (ς0,μ0)=(0.04±0.05,0.08-0.19+0.21) for the combination of all data, both at 68% confidence. Overall, we find no significant evidence for physics beyond ΛCDM

Manipulation of Costimulatory Molecules by Intracellular Pathogens: Veni, Vidi, Vici!!

Some of the most successful pathogens of human, such as Mycobacterium tuberculosis (Mtb), HIV, and Leishmania donovani not only establish chronic infections but also remain a grave global threat. These pathogens have developed innovative strategies to evade immune responses such as antigenic shift and drift, interference with antigen processing/presentation, subversion of phagocytosis, induction of immune regulatory pathways, and manipulation of the costimulatory molecules. Costimulatory molecules expressed on the surface of various cells play a decisive role in the initiation and sustenance of immunity. Exploitation of the “code of conduct” of costimulation pathways provides evolutionary incentive to the pathogens and thereby abates the functioning of the immune system. Here we review how Mtb, HIV, Leishmania sp., and other pathogens manipulate costimulatory molecules to establish chronic infection. Impairment by pathogens in the signaling events delivered by costimulatory molecules may be responsible for defective T-cell responses; consequently organisms grow unhindered in the host cells. This review summarizes the convergent devices that pathogens employ to tune and tame the immune system using costimulatory molecules. Studying host-pathogen interaction in context with costimulatory signals may unveil the molecular mechanism that will help in understanding the survival/death of the pathogens. We emphasize that the very same pathways can potentially be exploited to develop immunotherapeutic strategies to eliminate intracellular pathogens

SunPy - Python for Solar Physics

This paper presents SunPy (version 0.5), a community-developed Python package for solar physics. Python, a free, cross-platform, general-purpose, high-level programming language, has seen widespread adoption among the scientific community, resulting in the availability of a large number of software packages, from numerical computation (NumPy, SciPy) and machine learning (scikit-learn) to visualisation and plotting (matplotlib). SunPy is a data-analysis environment specialising in providing the software necessary to analyse solar and heliospheric data in Python. SunPy is open-source software (BSD licence) and has an open and transparent development workflow that anyone can contribute to. SunPy provides access to solar data through integration with the Virtual Solar Observatory (VSO), the Heliophysics Event Knowledgebase (HEK), and the HELiophysics Integrated Observatory (HELIO) webservices. It currently supports image data from major solar missions (e.g., SDO, SOHO, STEREO, and IRIS), time-series data from missions such as GOES, SDO/EVE, and PROBA2/LYRA, and radio spectra from e-Callisto and STEREO/SWAVES. We describe SunPy's functionality, provide examples of solar data analysis in SunPy, and show how Python-based solar data-analysis can leverage the many existing tools already available in Python. We discuss the future goals of the project and encourage interested users to become involved in the planning and development of SunPy

How genomics can help biodiversity conservation

The availability of public genomic resources can greatly assist biodiversity assessment, conservation, and restoration efforts by providing evidence for scientifically informed management decisions. Here we survey the main approaches and applications in biodiversity and conservation genomics, considering practical factors, such as cost, time, prerequisite skills, and current shortcomings of applications. Most approaches perform best in combination with reference genomes from the target species or closely related species. We review case studies to illustrate how reference genomes can facilitate biodiversity research and conservation across the tree of life. We conclude that the time is ripe to view reference genomes as fundamental resources and to integrate their use as a best practice in conservation genomics.info:eu-repo/semantics/publishedVersio