Hyperon Polarization along the Beam Direction Relative to the Second and Third Harmonic Event Planes in Isobar Collisions at sqrt[s_{NN}]=200 GeV.

The polarization of Λ and Λ[over ¯] hyperons along the beam direction has been measured relative to the second and third harmonic event planes in isobar Ru+Ru and Zr+Zr collisions at sqrt[s_{NN}]=200 GeV. This is the first experimental evidence of the hyperon polarization by the triangular flow originating from the initial density fluctuations. The amplitudes of the sine modulation for the second and third harmonic results are comparable in magnitude, increase from central to peripheral collisions, and show a mild p_{T} dependence. The azimuthal angle dependence of the polarization follows the vorticity pattern expected due to elliptic and triangular anisotropic flow, and qualitatively disagrees with most hydrodynamic model calculations based on thermal vorticity and shear induced contributions. The model results based on one of existing implementations of the shear contribution lead to a correct azimuthal angle dependence, but predict centrality and p_{T} dependence that still disagree with experimental measurements. Thus, our results provide stringent constraints on the thermal vorticity and shear-induced contributions to hyperon polarization. Comparison to previous measurements at RHIC and the LHC for the second-order harmonic results shows little dependence on the collision system size and collision energy.

Novel on-site follow-up and enhancement program (FEP) improves knowledge, clinical skills and enabling environment of skilled birth attendants in Nepal.

INTRODUCTION: Although great strides have been made in maternal and newborn health in Nepal, the maternal mortality ratio (MMR) is still high at 186 per 100,000 births. Many maternal deaths are preventable if there is access to a skilled birth attendant (SBA). The Ministry of Health and Population of Nepal launched the in-service SBA training program in 2007 and has trained over 10,000 SBAs to date. Evidence shows that one episode of training is not enough to retain skills. Therefore, the Nick Simons Institute (NSI) in collaboration with National Health Training Center (NHTC) devised a Follow-Up and Enhancement Program (FEP) in 2011 where the knowledge, clinical skills, and working environment of SBA graduates were assessed directly at their worksites. FEP allows on-site coaching and feedback so that graduates may continue to improve upon any gaps in their knowledge, skills, and working environment. This study aims to assess the effectiveness of FEP. METHODS: We used a mixed-methods research design. A total of 73 SBAs who had a pre-FEP assessment in 2016 were followed up for a post-FEP assessment in 2017. We also collected data from 3 additional districts (115 SBAs) that had not previously had FEP, to compare SBAs in FEP versus non-FEP districts. Qualitative data was collected from 16 health facilities on the perceptions, motivation, and satisfaction of stakeholders. RESULTS: Of the total 188 SBAs that were sampled, a one-time FEP increased knowledge scores by 9%, clinical skills scores by 29%, and enabling environment scores by 7%. The number of deliveries conducted improved with a one-time FEP, although this increase was not statistically significant. We found a trickle-down effect of working in a facility that has had prior FEP, with SBAs that have never had FEP improving their clinical skills. FEP was found to be a highly accepted program and is beneficial to SBAs, trainers, and the Hospital Management Committee (HFOMC). However, a one-time FEP is not sufficient in retaining clinical skills and knowledge. CONCLUSION: FEP is a highly effective program by both quantitative and qualitative evaluation. Our study suggests that FEP should be frequent and continuous to retain the knowledge and clinical skills of SBAs, motivate them through on-site coaching, and improve their working environment through direct feedback to the Ministry of Health and Population.

Measurements of the Elliptic and Triangular Azimuthal Anisotropies in Central

The elliptic (v_{2}) and triangular (v_{3}) azimuthal anisotropy coefficients in central ^{3}He+Au, d+Au, and p+Au collisions at sqrt[s_{NN}]=200 GeV are measured as a function of transverse momentum (p_{T}) at midrapidity (|η|<0.9), via the azimuthal angular correlation between two particles both at |η|<0.9. While the v_{2}(p_{T}) values depend on the colliding systems, the v_{3}(p_{T}) values are system independent within the uncertainties, suggesting an influence on eccentricity from subnucleonic fluctuations in these small-sized systems. These results also provide stringent constraints for the hydrodynamic modeling of these systems.

Observation of Directed Flow of Hypernuclei _{Λ}

We report here the first observation of directed flow (v_{1}) of the hypernuclei _{Λ}^{3}H and _{Λ}^{4}H in mid-central Au+Au collisions at sqrt[s_{NN}]=3 GeV at RHIC. These data are taken as part of the beam energy scan program carried out by the STAR experiment. From 165×10^{6} events in 5%-40% centrality, about 8400 _{Λ}^{3}H and 5200 _{Λ}^{4}H candidates are reconstructed through two- and three-body decay channels. We observe that these hypernuclei exhibit significant directed flow. Comparing to that of light nuclei, it is found that the midrapidity v_{1} slopes of _{Λ}^{3}H and _{Λ}^{4}H follow baryon number scaling, implying that the coalescence is the dominant mechanism for these hypernuclei production in the 3 GeV Au+Au collisions.

Beam Energy Dependence of Triton Production and Yield Ratio (N_{t}×N_{p}/N_{d}

We report the triton (t) production in midrapidity (|y|<0.5) Au+Au collisions at sqrt[s_{NN}]=7.7-200 GeV measured by the STAR experiment from the first phase of the beam energy scan at the Relativistic Heavy Ion Collider. The nuclear compound yield ratio (N_{t}×N_{p}/N_{d}^{2}), which is predicted to be sensitive to the fluctuation of local neutron density, is observed to decrease monotonically with increasing charged-particle multiplicity (dN_{ch}/dη) and follows a scaling behavior. The dN_{ch}/dη dependence of the yield ratio is compared to calculations from coalescence and thermal models. Enhancements in the yield ratios relative to the coalescence baseline are observed in the 0%-10% most central collisions at 19.6 and 27 GeV, with a significance of 2.3σ and 3.4σ, respectively, giving a combined significance of 4.1σ. The enhancements are not observed in peripheral collisions or model calculations without critical fluctuation, and decreases with a smaller p_{T} acceptance. The physics implications of these results on the QCD phase structure and the production mechanism of light nuclei in heavy-ion collisions are discussed.

Phase Ib study of talimogene laherparepvec in combination with atezolizumab in patients with triple negative breast cancer and colorectal cancer with liver metastases.

BACKGROUND: Talimogene laherparepvec (T-VEC), a first-in-class oncolytic viral immunotherapy, enhances tumor-specific immune activation. T-VEC combined with atezolizumab, which blocks inhibitor T-cell checkpoints, could provide greater benefit than either agent alone. Safety/efficacy of the combination was explored in patients with triple negative breast cancer (TNBC) or colorectal cancer (CRC) with liver metastases. METHODS: In this phase Ib, multicenter, open-label, parallel cohort study of adults with TNBC or CRC with liver metastases, T-VEC (106 then 108 PFU/ml; ≤4 ml) was administered into hepatic lesions via image-guided injection every 21 (±3) days. Atezolizumab 1200 mg was given on day 1 and every 21 (±3) days thereafter. Treatment continued until patients experienced dose-limiting toxicity (DLT), had complete response, progressive disease, needed alternative anticancer treatment, or withdrew due to an adverse event (AE). The primary endpoint was DLT incidence, and secondary endpoints included efficacy and AEs. RESULTS: Between 19 March 2018 and 6 November 2020, 11 patients with TNBC were enrolled (safety analysis set: n = 10); between 19 March 2018 and 16 October 2019, 25 patients with CRC were enrolled (safety analysis set: n = 24). For the 5 patients in the TNBC DLT analysis set, no patient had DLT; for the 18 patients in the CRC DLT analysis set, 3 (17%) had DLT, all serious AEs. AEs were reported by 9 (90%) TNBC and 23 (96%) CRC patients, the majority with grade ≥3 [TNBC, 7 (70%); CRC, 13 (54%)], and 1 was fatal [CRC, 1 (4%)]. Evidence of efficacy was limited. Overall response rate was 10% (95% confidence interval 0.3-44.5) for TNBC; one (10%) patient had a partial response. For CRC, no patients had a response; 14 (58%) were unassessable. CONCLUSIONS: The safety profile reflected known risks with T-VEC including risks of intrahepatic injection; no unexpected safety findings from addition of atezolizumab to T-VEC were observed. Limited evidence of antitumor activity was observed.

Measurement of Sequential ϒ Suppression in Au+Au Collisions at sqrt[s_{NN}]=200 GeV with the STAR Experiment.

We report on measurements of sequential ϒ suppression in Au+Au collisions at sqrt[s_{NN}]=200 GeV with the STAR detector at the Relativistic Heavy Ion Collider (RHIC) through both the dielectron and dimuon decay channels. In the 0%-60% centrality class, the nuclear modification factors (R_{AA}), which quantify the level of yield suppression in heavy-ion collisions compared to p+p collisions, for ϒ(1S) and ϒ(2S) are 0.40±0.03(stat)±0.03(sys)±0.09(norm) and 0.26±0.08(stat)±0.02(sys)±0.06(norm), respectively, while the upper limit of the ϒ(3S) R_{AA} is 0.17 at a 95% confidence level. This provides experimental evidence that the ϒ(3S) is significantly more suppressed than the ϒ(1S) at RHIC. The level of suppression for ϒ(1S) is comparable to that observed at the much higher collision energy at the Large Hadron Collider. These results point to the creation of a medium at RHIC whose temperature is sufficiently high to strongly suppress excited ϒ states.

Beam Energy Dependence of Fifth- and Sixth-Order Net-Proton Number Fluctuations in Au+Au Collisions at RHIC.

We report the beam energy and collision centrality dependence of fifth and sixth order cumulants (C_{5}, C_{6}) and factorial cumulants (κ_{5}, κ_{6}) of net-proton and proton number distributions, from center-of-mass energy (sqrt[s_{NN}]) 3 GeV to 200 GeV Au+Au collisions at RHIC. Cumulant ratios of net-proton (taken as proxy for net-baryon) distributions generally follow the hierarchy expected from QCD thermodynamics, except for the case of collisions at 3 GeV. The measured values of C_{6}/C_{2} for 0%-40% centrality collisions show progressively negative trend with decreasing energy, while it is positive for the lowest energy studied. These observed negative signs are consistent with QCD calculations (for baryon chemical potential, µ_{B}≤110 MeV) which contains the crossover transition range. In addition, for energies above 7.7 GeV, the measured proton κ_{n}, within uncertainties, does not support the two-component (Poisson+binomial) shape of proton number distributions that would be expected from a first-order phase transition. Taken in combination, the hyperorder proton number fluctuations suggest that the structure of QCD matter at high baryon density, µ_{B}∼750 MeV at sqrt[s_{NN}]=3 GeV is starkly different from those at vanishing µ_{B}∼24 MeV at sqrt[s_{NN}]=200 GeV and higher collision energies.

Arytenoid granuloma: a single-institution experience of management of 62 cases.

OBJECTIVE: This retrospective study was undertaken to assess the outcome of the medical and/or surgical management of patients presenting with clinical features of arytenoid granuloma. METHODS: The records of 53 males and 9 females were reviewed for predisposing factors, types of treatment received and recurrence following the treatment. RESULTS: Most of the patients (48 out of 62, 77.4 per cent) were treated conservatively with medical management and voice therapy, which resulted in complete resolution of arytenoid granuloma in over two-thirds of the patients treated (32 out of 48, 66.6 per cent). Overall, 28 patients (out of 62, 45.1 per cent) required surgery (14 failed medical treatment cases and 14 surgery as first-line treatment cases). Of these, five patients (out of 28, 17.9 per cent) had recurrence, and were managed with revision surgery and concurrent local injection of Botox. CONCLUSION: Anti-reflux medication and voice therapy are effective first-line management options. Pre- and post-surgery adjuvant treatment improves the results of surgery. Local injection of Botox was successful in the treatment of failed surgical cases.

A Comparative Study of Rapid SARS-Cov-2 Antigen Detection Assay against RT-PCR Assay for Diagnosis of COVID-19 in a Tertiary Hospital of Kathmandu.

Background The Coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) has spread worldwide since its first recorded case in the city of Wuhan, China, in December 2019. SARS-CoV-2 infection causes asymptomatic to sever pneumonia. Severe cases may develop acute respiratory disease symdrome (ARDS), with an average mortality rate of 6.9%. Real Time Reverse Transcriptase Polymerase Chain Reaction (rRT-PCR) assay is the current reference standard laboratory method for the diagnosis of SARS-CoV-2 infection. However, it takes around 6-8 hours to get the result and is time consuming. Therefore, rapid and accurate tests for SARS-CoV-2 screening are essential to expedite disease prevention and control. Lateral flow immunoassay using monoclonal anti SARS-CoV-2 antibodies which target for SARS-CoV-2 antigen can be complimentary screening test if their accuracy were comparable to that of the real time reverse transcriptionpolymerase chain reaction (RT-PCR) assay. Objective To find the sensitivity and specificity of a rapid antigentest kit in comparison to reverse transcription-polymerase chain reaction (RT-PCR). Method A cross-sectional hospital based study was carried out at Shree Birendra Army Hospital, Kathmandu for a period of four months. Result Our finding shows sensitivity and specificity of rapid diagnostic tests (RDT) Ag kit as 60.6% and 96.4% respectively. Positive and negative predictive value was 83.7% and 89.0%. Likewise, positive and negative likelihood ratio was 17.0 and 0.4. The overall accuracy of the antigen kit was 88.1% in comparison to reverse transcriptionpolymerase chain reaction (RT-PCR) as the gold standard. Conclusion Our study concluded the use of rapid antigen kit is mainly useful for screening purposes.

Otorhinolaryngological manifestations of coronavirus disease 2019: a prospective review of 600 patients.

OBJECTIVES: To evaluate otorhinolaryngological manifestations of coronavirus disease 2019 infection and the time required for their resolution. METHODS: A prospective analysis was conducted of coronavirus disease 2019 patients presenting from 1 April 2020 to 30 July 2020. The otorhinolaryngological manifestations were evaluated based on patient history. The time required for symptom resolution was evaluated separately for intensive care unit and non-intensive care unit patients. RESULTS: A total of 600 patients were included in the study; 13.3 per cent required the intensive care unit and 2.2 per cent expired. The otorhinolaryngological manifestations were: sore throat (88 per cent), fever (78.8 per cent), anosmia or hyposmia (63.6 per cent), ageusia or hypogeusia (63.5 per cent), rhinorrhoea (51.3 per cent), nasal obstruction (33.5 per cent), sneezing (30.3 per cent), and breathing difficulty (18.6 per cent). The time required for symptom resolution was longest for breathing difficulty (23.6 days for intensive care unit and 8.2 days for non-intensive care unit patients). CONCLUSION: Otorhinolaryngological symptoms are one of the main presentations of coronavirus disease 2019 infection. The increased prevalence of medical co-morbidities in patients requiring intensive care unit and in deceased patients is also highlighted.

Obstetric consequences of subfertility: a retrospective cohort study.

OBJECTIVE: To compare the risk of adverse pregnancy outcomes in women with and without subfertility and to investigate whether fertility treatment contributes to the adverse outcomes. DESIGN: Register-based retrospective cohort study. SETTING: Aberdeen, Scotland POPULATION: The exposed group included women with subfertility attending Aberdeen Fertility Clinic between 1989 and 2008 and delivering a singleton (n = 3188) or twin (n = 350) at Aberdeen Maternity Hospital between 1992 and 2009. The unexposed cohort included the remainder of women (singleton n = 52443, twin n = 1125) delivering at Aberdeen Maternity Hospital between 1992 and 2009. METHODS: The Aberdeen Fertility Centre database and Aberdeen Maternity and Neonatal Databank were linked using Community Health Index numbers. Regression models were used to calculate risk ratios and 95% confidence intervals adjusting for potential confounders. MAIN OUTCOME MEASURES: Maternal outcomes including pre-eclampsia, antepartum haemorrhage, preterm birth, induction of labour; delivery outcomes including operative vaginal delivery, caesarean section; and offspring outcomes including low birthweight, stillbirth and neonatal death. RESULTS: Women with a history of subfertility who delivered a singleton were at a higher risk of pre-eclampsia [adjusted risk ratios (aRR) 1.18, 95% confidence intervals (CI) 1.02-1.37], antepartum haemorrhage (aRR 1.32, 95% CI 1.18-1.47), induction of labour (aRR 1.21, 95% CI 1.11-1.31) and very preterm delivery (<32 weeks) (aRR 1.96, 95% CI 1.53-2.49). Subfertile women delivering twins were at a higher risk of being delivered by emergency caesarean section (aRR 2.14, 95% CI 1.26-3.66). There were no significant differences in adverse outcomes for singleton pregnancies between the treated and untreated subfertile couples. CONCLUSION: Subfertility per se, rather than fertility treatment, was associated with increased risk of adverse outcomes in singleton pregnancies. TWEETABLE ABSTRACT: Large cohort study found higher incidence of adverse outcome in subfertile women having singletons or twins.

Impact of diabetes on inpatient mortality and length of stay for elderly patients presenting with fracture of the proximal femur.

INTRODUCTION: Osteoporosis-related fractures of the proximal femur cause significant morbidity and result in an economic burden on societies. It remains debatable whether diabetic patients with proximal fracture of the femur demonstrate poorer outcomes in terms of hospital stay and mortality compared to non-diabetic controls. METHODS: All patients over 65years old admitted to the University Hospital Birmingham during 2007-2010 with a diagnosis of a fracture of the proximal femur (total 1468 including 197 patients with diabetes) were analysed. Eligibility and case definitions were ascertained using electronic records. Multivariate analyses were conducted to control for the confounding effect of covariates, which may be associated with the outcomes of interest on the basis of biological plausibility and known risks. RESULTS: In-patient mortality was estimated at 14.2% and 12% for the diabetic and non-diabetic patients respectively. Diabetes was not found to be a significant predictor of in-patient mortality, before and after adjustment for the covariates [Adjusted odds ratio 1.01 (95% CI 0.62-1.65)], in contrast to advancing age, male gender, co-morbidity score, low albumin and high creatinine concentrations. Similarly, median length of stay was greater in the diabetes patients, yet only by a day (20 versus 19 days). This was not statistically significant in either the unadjusted (p=0.17) or in the multivariate analysis (p=0.06). CONCLUSIONS: Diabetic patients admitted with fracture of the proximal femur did not demonstrate significantly poorer outcomes in terms of in-patient mortality and length of stay compared to non-diabetic patients.

Transcriptional signatures mediated by acetylation overlap with early-stage Alzheimer's disease.

The mechanisms by which environmental influences lead to the development of complex neurodegenerative diseases are largely unknown. It is known, however, that epigenetic mechanisms can mediate alterations in transcription due to environmental influences. In order to identify genes susceptible to regulation in the adult cortex by one type of epigenetic mechanism, histone, and protein acetylation, we treated mice with the histone deacetylase inhibitor Trichostatin A (TSA). After 1 week of treatment with TSA, RNA was extracted from the brain cortices of mice and gene expression differences were analyzed by microarray profiling. The altered genes were then compared with genes differentially expressed in microarray studies of disease by database and literature searches. Genes regulated by TSA were found to significantly overlap with differentially expressed genes in the Alzheimer's disease (AD) brain. Several TSA-regulated genes involved in chromatin remodeling and epigenetic reprogramming including histone cluster 1, H4 h (Hist1H4 h), methionine adenosyltransferase II, alpha (Mat2a), and 5-methyltetrahydrofolate homocysteine reductase (Mtrr) overlapped with genes altered in early-stage AD in gray matter. We also show that the expression of hemoglobin, which has been shown to be altered in neurons in the AD brain, is regulated by TSA treatment. This analysis suggests involvement of epigenetic mechanisms in neurons in early stages of AD.

Pelvic girdle pain during pregnancy and puerperium.

Pelvic girdle pain (PGP) is a term used specifically to pregnancy-related pain in the lumbosacral, sacroiliac and symphysis pubis joints. Pregnancy-induced hormonal and physical changes increase the risk of musculoskeletal problems in pregnancy. The severity of these conditions varies from mild self-limiting pain to a severe disabling condition. PGP is common in pregnancy and while most can be managed as outpatients, a few patients require inpatient admission for further investigations and management. Prompt identification of these conditions is essential to avoid serious disability. Lack of awareness and failure of recognition not only results in women feeling isolated, but may also result in long-term morbidity. In this review, we explore the aetiology, presentation, risk factors, risk of recurrence, differential diagnosis and multidisciplinary management of these conditions. We also enclose obstetric guidelines to increase the awareness of the health professionals.

Doppel-induced apoptosis and counteraction by cellular prion protein in neuroblastoma and astrocytes.

Expression of a prion-like protein, doppel, induces apoptosis-like changes in cerebellar neuronal granule and Purkinje cells of prion-knockout mice and this effect can be rescued by re-introduction of cellular prion. Since most of those studies were done in transgenic mice, in the present study, we have established a murine neuro-2a cell line and the primary rat adult reactive astrocyte model for studying doppel-induced apoptosis and possible prion counteraction. We demonstrate that expression of doppel in neuro-2a cells causes apoptosis, during which DNA fragmentation occurs as visualized by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling staining and other intracellular changes characteristic of apoptosis are observed in the electron microscope. Using immunoblot analyses, we further demonstrate that doppel expression activates caspase-10 as well as caspase-3, but does not activate caspase-9. Addition of purified doppel to cultures of neuro-2a cells and the primary astrocytes causes similar apoptotic changes. Significantly, apoptosis induced by doppel is enhanced when cellular prion protein is depleted by RNA interference, suggesting a protective effect of cellular prion against doppel-induced apoptosis. The antagonistic interaction between cellular prion and doppel appears to involve direct protein-protein interaction possibly on cell membrane as cellular prion and doppel physically interact with each other and co-localize on cell membranes. Together, our data show that doppel induces apoptosis in neuroblastoma neuro-2a and rat primary astrocytes via a caspase-10 mediated pathway and that this effect is counteracted by cellular prion through direct interaction with doppel possibly on cell membrane.

Bile salt-stimulated lipase in the milk of Fulani and Kanuri women in Nigeria and native Nepalese women.

Human milk provides newborns with several physiologically important proteins not found in cow's milk, including bile salt-stimulated lipase (BSSL) that compensates for the reduced lipolytic capability of the newborn intestine. We analyzed the milk of two ethnically distinct groups of women in northern Nigeria and Nepal. The milk of the Nepalese women (n = 36) contained slightly more BSSL activity (mean, 38.8 units/mL) than that of Fulani (n = 48; mean, 30.3 units/mL) and Kanuri (n = 90; mean 27.6 units/mL) women in Nigeria. There was also a weak positive correlation between the BSSL content of the milk and the body mass index (BMI) of the lactating women. The BSSL activity declined with the length of lactation for both well-nourished and undernourished women. The presence of a heat-stable inhibitor of BSSL in cow's milk was also demonstrated. This finding, along with the decrease in BSSL activity postgestation, could be of significance to populations such as the Fulani of the western Sahel who supplement the diets of their infants with unpasteurized cow's milk.

Innovative pharmacologic approaches to cardiopulmonary resuscitation.

The survival rate of patients undergoing cardiopulmonary resuscitation (CPR) is 5% to 15%. New treatment approaches under investigation for CPR include the use of vasopressin as a vasopressor, amiodarone for the treatment of ventricular tachyarrhythmia, and adenosine antagonists (i.e., theophylline) for bradyasystolic rhythms. More innovative approaches include the use of thyroid hormone and endothelin.