HYPER-RESPONSIVENESS OF ALDOSTERONE TO METOCLOPRAMIDE IN ALDOSTERONISM

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73101/1/j.1365-2265.1982.tb02761.x.pd

Flares, wind and nebulae: the 2015 December mini-outburst of V404 Cygni

After more than 26 years in quiescence, the black hole transient V404 Cyg went into a luminous outburst in June 2015, and additional activity was detected in late December of the same year. Here, we present an optical spectroscopic follow-up of the December mini-outburst, together with X-ray, optical and radio monitoring that spanned more than a month. Strong flares with gradually increasing intensity are detected in the three spectral ranges during the ∼ 10 days following the Swift trigger. Our optical spectra reveal the presence of a fast outflowing wind, as implied by the detection of a P-Cyg profile (He i–5876 ˚A) with a terminal velocity of ∼ 2500 kms−1 . Nebularlike spectra – with an H α equivalent width of ∼ 500 ˚A – are also observed. All these features are similar to those seen during the main June 2015 outburst. Thus, the fast optical wind simultaneous with the radio jet is most likely present in every V404 Cyg outburst. Finally, we report on the detection of a strong radio flare in late January 2016, when X-ray and optical monitoring had stopped due to Sun constraints

Clinical spectrum of SIX3-associated mutations in holoprosencephaly: correlation between genotype, phenotype and function

BACKGROUND: Holoprosencephaly (HPE) is the most common structural malformation of the human forebrain. There are several important HPE mutational target genes, including the transcription factor SIX3, which encodes an early regulator of Shh, Wnt, Bmp and Nodal signalling expressed in the developing forebrain and eyes of all vertebrates. OBJECTIVE: To characterise genetic and clinical findings in patients with SIX3 mutations. METHODS: Patients with HPE and their family members were tested for mutations in HPE-associated genes and the genetic and clinical findings, including those for additional cases found in the literature, were analysed. The results were correlated with a mutation-specific functional assay in zebrafish. RESULTS: In a cohort of patients (n = 800) with HPE, SIX3 mutations were found in 4.7% of probands and additional cases were found through testing of relatives. In total, 138 cases of HPE were identified, 59 of whom had not previously been clinically presented. Mutations in SIX3 result in more severe HPE than in other cases of non-chromosomal, non-syndromic HPE. An over-representation of severe HPE was found in patients whose mutations confer greater loss of function, as measured by the functional zebrafish assay. The gender ratio in this combined set of patients was 1.5:1 (F:M) and maternal inheritance was almost twice as common as paternal. About 14% of SIX3 mutations in probands occur de novo. There is a wide intrafamilial clinical range of features and classical penetrance is estimated to be at least 62%. CONCLUSIONS: Our data suggest that SIX3 mutations result in relatively severe HPE and that there is a genotype-phenotype correlation, as shown by functional studies using animal models

AMI-CL J0300+2613: a Galactic anomalous-microwave-emission ring masquerading as a galaxy cluster

Large scale structure and cosmolog

HER2-enriched subtype and pathological complete response in HER2-positive breast cancer: A systematic review and meta-analysis

Background: HER2-positive (HER2+) breast cancer (BC) comprises all the four PAM50 molecular subtypes. Among these, the HER2-Enriched (HER2-E) appear to be associated with higher pathological complete response (pCR) rates following anti-HER2-based regimens. Here, we present a meta-analysis to validate the association of the HER2-E subtype with pCR following anti-HER2-based neoadjuvant treatments with or without chemotherapy (CT). Methods: A systematic literature search was performed in February 2019. The primary objective was to compare the association between HER2-E subtype (versus others) and pCR. Selected secondary objectives were to compare the association between 1) HER2-E subtype and pCR in CT-free studies, 2) HER2-E subtype within hormone receptor (HR)-negative and HR+ disease and 3) HR-negative disease (versus HR+) and pCR in all patients and within HER2-E subtype. A random-effect model was applied. The Higgins’ I2 was used to quantify heterogeneity. Results: Sixteen studies were included, 5 of which tested CT-free regimens. HER2-E subtype was significantly associated with pCR in all patients (odds ratio [OR] = 3.50, p < 0.001, I2 = 33%), in HR+ (OR = 3.61, p < 0.001, I2 = 1%) and HR-negative tumors (OR = 2.28, p = 0.01, I2 = 47%). In CT-free studies, HER2-E subtype was associated with pCR in all patients (OR = 5.52, p < 0.001, I2 = 0%) and in HR + disease (OR = 4.08, p = 0.001, I2 = 0%). HR-negative status was significantly associated with pCR compared to HR + status in all patients (OR = 2.41, p < 0.001, I2 = 30%) and within the HER2-E subtype (OR = 1.76, p < 0.001, I2 = 0%). Conclusions: The HER2-E biomarker identifies patients with a higher likelihood of achieving a pCR following neoadjuvant anti-HER2-based therapy beyond HR status and CT use. Future trial designs to escalate or de-escalate systemic therapy in HER2+ disease should consider this genomic biomarker

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

The migration of bitumens through fracture systems

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN038073 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Identifying targets for conservation: the arrival and loss of Common Eider <i>Somateria mollissima</i> ducklings in an estuarine nursery

The arrival of Common Eider Somateria mollissima ducklings into a reception and nursery area is a measure of breeding success and phenology but reveals gaps in knowledge for effective conservation. Estuarine habitats are important wildlife areas but are continually under threat from human activities. Common Eiders may be an indicator species for monitoring the impacts of development in estuaries used by them as nursery areas. The aim of this study was to understand the arrival and distribution of ducklings in a commercial and recreational estuarine environment. Coquet Island, Northumberland, is a breeding site for Common Eiders at the southern limit of their range on the east coast of the UK. Numbers of ducklings arriving in the adjacent Coquet Estuary nursery area were monitored daily during the breeding season over a 27-year period from 1995 to 2021 inclusive. Counts of ducklings were higher overall in less disturbed parts of the estuary, but there were no consistent patterns of habitat use. First-arrival dates varied annually by up to 23 days. Daily arrival counts were affected by tide and, to a lesser extent, rain and wind direction. Observed arrivals each season correlated with counts of breeding females on Coquet Island. There was evidence for links between broader-scale weather conditions (North Atlantic Oscillation indices) and yearly variation in rates of duckling arrival. Arrivals were more synchronous in years when ducklings were late in arriving and supported theoretical predictions from modelling studies. There were high daily rates of duckling loss from the estuary which may have been a consequence of brood movements out of the estuary and loss to predation. There was a positive correlation between counts of ducklings and attendant females. Annual duckling counts show the value of estuaries for monitoring phenological variation in the breeding of Common Eiders. A better understanding of environmental factors influencing duckling retention or loss in estuaries is needed. Enabling human and wildlife activities to exist together within estuarine environments may promote effective conservation.</p