On using visibility correlations to probe the HI distribution from the dark ages to the present epoch I: Formalism and the expected signal

Redshifted 21 cm radiation originating from the cosmological distribution of neutral hydrogen (HI) appears as a background radiation in low frequency radio observations. The angular and frequency domain fluctuations in this radiation carry information about cosmological structure formation. We propose that correlations between visibilities measured at different baselines and frequencies in radio-interferometric observations be used to quantify the statistical properties of these fluctuations. This has an inherent advantage over other statistical estimators in that it deals directly with the visibilities which are the primary quantities measured in radio-interferometric observations. Also, the visibility correlation has a very simple relation with power spectrum. We present estimates of the expected signal for nearly the entire post-recombination era, from the dark ages to the present epoch. The epoch of reionization, where the HI has a patchy distribution, has a distinct signature where the signal is determined by the size of the discrete ionized regions. The signal at other epochs, where the HI follows the dark matter, is determined largely by the power spectrum of dark matter fluctuations. The signal is strongest for baselines where the antenna separations are within a few hundred times the wavelength of observation, and an optimal strategy would preferentially sample these baselines. In the frequency domain, for most baselines the visibilities at two different frequencies are uncorrelated beyond \Delta \nu ~ 1 MHz, a signature which in principle would allow the HI signal to be easily distinguished from the continuum sources of contamination.Comment: 12 pages, 9 figures, Accepted to MNRAS; Replaced to match version accepted in MNRA

Global Burden of Double Malnutrition: Has Anyone Seen It?

Background. Low- to middle-income countries (LMICs) are believed to be characterized by the coexistence of underweight and overweight. It has also been posited that such coexistence is appearing among the low socioeconomic status (SES) groups. Methods. We conducted a cross-sectional analysis of nationally representative samples of 451321 women aged 20–49 years drawn from 57 Demographic and Health Surveys conducted between 1994 and 2008. Body Mass Index (BMI in $kg/m^2$), was used to define underweight and overweight following conventional cut-points. Covariates included age, household wealth, education, and residence. We estimated multinomial multilevel models to assess the extent to which underweight $(BMI<18.5 kg/m^2)$ and overweight $(BMI≥25.0 kg/m^2)$ correlate at the country-level, and at the neighborhood-level within each country. Results. In age-adjusted models, there was a strong negative correlation between likelihood of being underweight and overweight at country- (r = −0.79, p<0.001), and at the neighborhood-level within countries (r = −0.51, P<0.001). Negative correlations ranging from −0.11 to −0.90 were observed in 46 of the 57 countries at the neighborhood-level and 29/57 were statistically significant $(p\leq 0.05)$. Similar negative correlations were observed in analyses restricted to low SES groups. Finally, the negative correlations across countries, and within-countries, appeared to be stable over time in a sub-set of 36 countries. Conclusion. The explicitly negative correlations between prevalence of underweight and overweight at the country-level and at neighborhood-level suggest that the hypothesized coexistence of underweight and overweight has not yet occurred in a substantial manner in a majority of LMICs

A systematic review highlighting poor quality of evidence for content validity of quality of life instruments in female chronic pelvic pain.

OBJECTIVES: To evaluate the content validity of 19 patient-reported outcome measures (PROMs) used to measure quality of life (QoL) in women with chronic pelvic pain (CPP). STUDY DESIGN AND SETTING: We searched Embase, MEDLINE, PsycINFO databases and Google Scholar from inception to August 2020. We included records describing the development or studies assessing content validity of PROMs. Two reviewers independently assessed the methodological quality of PROMs using the Consensus-based Standards for the Selection of Health Measurement Instruments checklist. Evidence was synthesized for relevance, comprehensiveness, and comprehensibility. Quality of evidence was rated using a modified Grading of Recommendations, Assessment, Development, and Evaluations approach. RESULTS: PROM development was inadequate for all instruments included in this review. No high-quality evidence ratings were found for relevance, comprehensiveness, and comprehensibility. QoL was measured using generic instruments (68.42%, 13/19) rather than those specific to chronic pain (21.04%, 4/19) or pelvic pain (10.53%, 2/19). Quality of concept elicitation was inadequate for 90% of PROMs. Half of PROMs did not include patients in their development and only 40% were devised using a sample representative of the target population for which the PROM was developed. Cognitive interviews were conducted in one-fifth of PROMs and were mostly of inadequate/doubtful quality. CONCLUSION: There is poor quality of evidence for content validity of PROMs used to measure QoL in women with CPP

A meta-synthesis of qualitative literature on female chronic pelvic pain for the development of a core outcome set: a systematic review.

INTRODUCTION AND HYPOTHESIS: Qualitative research has an increasing role in the development of core outcome sets (COS) adding patient perspectives to the considerations of core outcomes. We aimed to identify priorities of women with experience of chronic pelvic pain (CPP). METHODS: The search strategy was a systematic review of qualitative studies identified from Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, EMBASE, MEDLINE and PsycInfo databases. Selection criteria were qualitative studies exploring the experience of women with CPP. Two independent researchers extracted data and summarized findings using thematic analysis. A CERQual assessment was performed to assess the confidence of review findings. RESULTS: We identified pertinent issues affecting women with CPP including the lack of holistic care, influence of psychosocial factors and the impact of pain on quality of life. Five meta-themes central to delivering a patient-centred approach were highlighted: acceptance of pain, quality of life, management of CPP, communication and support. Management of CPP was the most commonly reported meta-theme across seven studies and half of studies reported quality of life, management, communication and support. Quality appraisal of included studies identified only a single study that met all CASP (Critical Appraisal Skills Programme) criteria. There was high confidence in the evidence for acceptance of pain, quality of life and communication meta-themes. CONCLUSION: Meta-themes revealed by this review should be considered as a priority and reflected in outcomes reported by future studies evaluating interventions for CPP. In addition, these themes should be considered by clinicians managing women with CPP

Evaluation of clinical practice guidelines (CPG) on the management of female chronic pelvic pain (CPP) using the AGREE II instrument.

INTRODUCTION AND HYPOTHESIS: Variations in guidelines may result in differences in treatments and potentially poorer health-related outcomes. We aimed to systematically review and evaluate the quality of national and international guidelines and create an inventory of CPG recommendations on CPP. METHODS: We searched EMBASE and MEDLINE databases from inception till August 2020 as well as websites of professional organizations and societies. We selected national and international CPGs reporting on the diagnosis and management of female CPP. We included six CPGs. Five researchers independently assessed the quality of included guidelines using the AGREE II tool and extracted recommendations. RESULTS: Two hundred thirty-two recommendations were recorded and grouped into six categories: diagnosis, medical treatment, surgical management, behavioural interventions, complementary/alternative therapies and education/research. Thirty-nine (17.11%) recommendations were comparable including: a comprehensive pain history, a multi-disciplinary approach, attributing muscular dysfunction as a cause of CPP and an assessment of quality of life. Two guidelines acknowledged sexual dysfunction associated with CPP and recommended treatment with pelvic floor exercises and behavioural interventions. All guidelines recommended surgical management; however, there was no consensus regarding adhesiolysis, bilateral salpingo-oophorectomy during hysterectomy, neurectomy and laparoscopic uterosacral nerve ablation. Half of recommendations (106, 46.49%) were unreferenced or made in absence of good-quality evidence or supported by expert opinion. Based on the AGREE II assessment, two guidelines were graded as high quality and recommended without modifications (EAU and RCOG). Guidelines performed poorly in the "Applicability", "Editorial Independence" and "Stakeholder Involvement" domains. CONCLUSION: Majority of guidelines were of moderate quality with significant variation in recommendations and quality of guideline development

Mapping Dynamic Histone Acetylation Patterns to Gene Expression in Nanog-depleted Murine Embryonic Stem Cells

Embryonic stem cells (ESC) have the potential to self-renew indefinitely and to differentiate into any of the three germ layers. The molecular mechanisms for self-renewal, maintenance of pluripotency and lineage specification are poorly understood, but recent results point to a key role for epigenetic mechanisms. In this study, we focus on quantifying the impact of histone 3 acetylation (H3K9,14ac) on gene expression in murine embryonic stem cells. We analyze genome-wide histone acetylation patterns and gene expression profiles measured over the first five days of cell differentiation triggered by silencing Nanog, a key transcription factor in ESC regulation. We explore the temporal and spatial dynamics of histone acetylation data and its correlation with gene expression using supervised and unsupervised statistical models. On a genome-wide scale, changes in acetylation are significantly correlated to changes in mRNA expression and, surprisingly, this coherence increases over time. We quantify the predictive power of histone acetylation for gene expression changes in a balanced cross-validation procedure. In an in-depth study we focus on genes central to the regulatory network of Mouse ESC, including those identified in a recent genome-wide RNAi screen and in the PluriNet, a computationally derived stem cell signature. We find that compared to the rest of the genome, ESC-specific genes show significantly more acetylation signal and a much stronger decrease in acetylation over time, which is often not reflected in an concordant expression change. These results shed light on the complexity of the relationship between histone acetylation and gene expression and are a step forward to dissect the multilayer regulatory mechanisms that determine stem cell fate.Comment: accepted at PLoS Computational Biolog

Poor birth weight recovery among low birth weight/preterm infants following hospital discharge in Kampala, Uganda

<p>Abstract</p> <p>Background</p> <p>Healthy infants typically regain their birth weight by 21 days of age; however, failure to do so may be due to medical, nutritional or environmental factors. Globally, the incidence of low birth weight deliveries is high, but few studies have assessed the postnatal weight changes in this category of infants, especially in Africa. The aim was to determine what proportion of LBW infants had not regained their birth weight by 21 days of age after discharge from the Special Care Unit of Mulago hospital, Kampala.</p> <p>Methods</p> <p>A cross sectional study was conducted assessing weight recovery of 235 LBW infants attending the Kangaroo Clinic in the Special Care Unit of Mulago Hospital between January and April 2010. Infants aged 21 days with a documented birth weight and whose mothers gave consent to participate were included in the study. Baseline information was collected on demographic characteristics, history on pregnancy, delivery and postnatal outcome through interviews. Pertinent infant information like gestation age, diagnosis and management was obtained from the medical records and summarized in the case report forms.</p> <p>Results</p> <p>Of the 235 LBW infants, 113 (48.1%) had not regained their birth weight by 21 days. Duration of hospitalization for more than 7 days (AOR: 4.2; 95% CI: 2.3 - 7.6; p value < 0.001) and initiation of the first feed after 48 hours (AOR: 1.9; 95% CI 1.1 - 3.4 p value 0.034) were independently associated with failure to regain birth weight. Maternal factors and the infant's physical examination findings were not significantly associated with failure to regain birth weight by 21 days of age.</p> <p>Conclusion</p> <p>Failure to regain birth weight among LBW infants by 21 days of age is a common problem in Mulago Hospital occurring in almost half of the neonates attending the Kangaroo clinic. Currently, the burden of morbidity in this group of high-risk infants is undetected and unaddressed in many developing countries. Measures for consideration to improve care of these infants would include; discharge after regaining birth weight and use of total parenteral nutrition. However, due to the pressure of space, keeping the baby and mother is not feasible at the moment hence the need for a strong community system to boost care of the infant. Close networking with support groups within the child's environment could help alleviate this problem.</p

Human Mas-related G protein-coupled receptors-X1 induce chemokine receptor 2 expression in rat dorsal root ganglia neurons and release of chemokine ligand 2 from the human LAD-2 mast cell line

Primate-specific Mas-related G protein-coupled receptors-X1 (MRGPR-X1) are highly enriched in dorsal root ganglia (DRG) neurons and induce acute pain. Herein, we analyzed effects of MRGPR-X1 on serum response factors (SRF) or nuclear factors of activated T cells (NFAT), which control expression of various markers of chronic pain. Using HEK293, DRG neuron-derived F11 cells and cultured rat DRG neurons recombinantly expressing human MRGPR-X1, we found activation of a SRF reporter gene construct and induction of the early growth response protein-1 via extracellular signal-regulated kinases-1/2 known to play a significant role in the development of inflammatory pain. Furthermore, we observed MRGPR-X1-induced up-regulation of the chemokine receptor 2 (CCR2) via NFAT, which is considered as a key event in the onset of neuropathic pain and, so far, has not yet been described for any endogenous neuropeptide. Up-regulation of CCR2 is often associated with increased release of its endogenous agonist chemokine ligand 2 (CCL2). We also found MRGPR-X1-promoted release of CCL2 in a human connective tissue mast cell line endogenously expressing MRGPR-X1. Thus, we provide first evidence to suggest that MRGPR-X1 induce expression of chronic pain markers in DRG neurons and propose a so far unidentified signaling circuit that enhances chemokine signaling by acting on two distinct yet functionally co-operating cell types. Given the important role of chemokine signaling in pain chronification, we propose that interruption of this signaling circuit might be a promising new strategy to alleviate chemokine-promoted pain

Synthesis and characterization of PCU@C-Ag/AgCl nanoparticles as an antimicrobial material for respiratory tract infection

Abstract The pregnant cow urine (PCU) is an active source of antimicrobial agents that is used for fabricating chitosan coated Ag/AgCl nanoparticles (NPs) in the present study. These PCU@C-Ag/AgCl NPs were physicochemically characterized and evaluated for antimicrobial activity against selected respiratory tract infection (RTI) pathogens. The absorption band around 420 nm in UV-Visible spectrum indicated the presence of Ag NPs. The spherical shape of NPs was observed using TEM. Also, the crystalline structure was confirmed using the XRD pattern. The PCU@C-Ag/AgCl NPs showed strong antimicrobial activity against all tested RTI pathogens. In addition, FESEM analysis showed morphological changes in RTI bacterial pathogens. Thereby, PCU@C-Ag/AgCl NPs may be used as an antimicrobial material to treat RTIs in near future at clinical level.</jats:p

Risk Factors for Nonsynchronous Second Primary Malignancy and Related Death in Patients with Differentiated Thyroid Carcinoma

BACKGROUND: Differentiated thyroid cancer (DTC) survivors are at increased risk of developing nonsynchronous second primary malignancy (NSPM). This study aims to examine possible risk factors leading to occurrence of NSPM as well as risk factors leading to NSPM-related death in patients with DTC. METHODS: Of the 1,106 patients with DTC managed at our institution, 92 (8.3%) patients developed NSPM and 40 (3.6%) patients died of NSPM. All causes of death were confirmed by medical record, autopsy report or death certificate. Clinicopathological variables were compared between those without NSPM and with NSPM as well as between those who died of NSPM and did not die of NSPM. Significant variables on univariate analysis were entered into a Cox proportional hazards model. RESULTS: The median latency period from diagnosis of DTC to NSPM was 142.7 (range 16.8-511.0) months. For occurrence of NSPM, age at DTC diagnosis >/=50 years old [relative risk (RR) = 2.35], cumulative radioactive iodine (RAI) activity 3.0-8.9 GBq (RR = 2.38), and external local radiotherapy (ERT) (RR = 1.95) were significant risk factors. For NSPM-related death, age at DTC diagnosis >/=50 years old (RR = 3.32) and nonbreast cancer (RR = 5.76) were significant risk factors. CONCLUSIONS: NSPM accounted for 18.7% of all deaths in DTC, but mortality was high (43.5%). Age at DTC diagnosis >/=50 years old, cumulative RAI activity 3.0-8.9 GBq, and ERT were significant risk factors for occurrence of NSPM, whereas age at DTC diagnosis >/=50 years old and the diagnosis of nonbreast cancer were significant risk factors for NSPM-related death.published_or_final_versionSpringer Open Choice, 21 Feb 201