Regulation of papillary plasma flow by angiotensin II

Regulation of papillary plasma flow by angiotensin II. We examined in anesthetized dogs the effects of left (L) intrarenal artery infusion of angiotensin II (AII) on renal hemodynamics, urinary concentration and Na excretion, and papillary plasma flow (PPF) (measured by the albumin accumulation technique) in both kidneys. Following AII infusion (0.5 ng/kg/min) into the L renal artery, urinary Na excretion decreased and osmolality increased slightly ipsilaterally, whereas Na excretion did not change significantly and osmolality decreased in the right (R) kidney. PPF was significantly lower in the L compared to the R kidney. When saline loading was superimposed on L intrarenal AII infusion, there was a blunted natriuretic response ipsilaterally with a significantly smaller decrease in urine osmolality compared with the R kidney. PPF increased significantly in the R, but not in the L kidney. Finally, AII blockade with saralasin prior to AII infusion and saline loading prevented the differences between the two kidneys, including PPF. In all groups GFR and renal blood flow did not differ between the two kidneys before or after AII. These data suggest that AII regulates regional blood flow in the medulla, and that the exogenously administered AII induces papillary ischemia, which serves to preserve medullary hypertonicity, preventing an increase in PPF during saline loading, and possibly contributing to the diminished natriuretic response

Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study.

Ulcerative colitis is a chronic inflammatory disease of the colon that presents as diarrhea and gastrointestinal bleeding. We performed a genome-wide association study using DNA samples from 1,052 individuals with ulcerative colitis and preexisting data from 2,571 controls, all of European ancestry. In an analysis that controlled for gender and population structure, ulcerative colitis loci attaining genome-wide significance and subsequent replication in two independent populations were identified on chromosomes 1p36 (rs6426833, combined P = 5.1 x 10(-13), combined odds ratio OR = 0.73) and 12q15 (rs1558744, combined P = 2.5 x 10(-12), combined OR = 1.35). In addition, combined genome-wide significant evidence for association was found in a region spanning BTNL2 to HLA-DQB1 on chromosome 6p21 (rs2395185, combined P = 1.0 x 10(-16), combined OR = 0.66) and at the IL23R locus on chromosome 1p31 (rs11209026, combined P = 1.3 x 10(-8), combined OR = 0.56; rs10889677, combined P = 1.3 x 10(-8), combined OR = 1.29)

The EBLM project. VII. Spin-orbit alignment for the circumbinary planet host EBLM J0608-59 A/TOI-1338 A

Funding: This work was inpart funded by the U.S.–Norway Fulbright Foundation and a NASATESSGI grant G022253 (PI: Martin). AHMJT received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant 803193/BEBOP), and from a Leverhulme Trust Research Project grant (RPG-2018-418). VKH is also supported by a Birmingham Doctoral Scholarship, and by a studentship from Birmingham’s School of Physics & Astronomy. DVM received funding from the Swiss National Science Foundation (grant P 400P2 186735). SG has been supported by STFC through consolidated grants ST/L000733/1and ST/P000495/1.A dozen short-period detached binaries are known to host transiting circumbinary planets. In all circumbinary systems so far, the planetary and binary orbits are aligned within a couple of degrees. However, the obliquity of the primary star, which is an important tracer of their formation, evolution, and tidal history, has only been measured in one circumbinary system until now. EBLM J0608-59/TOI-1338 is a low-mass eclipsing binary system with a recently discovered circumbinary planet identified by TESS. Here, we perform high-resolution spectroscopy during primary eclipse to measure the projected stellar obliquity of the primary component. The obliquity is low, and thus the primary star is aligned with the binary and planetary orbits with a projected spin-orbit angle β = 2.°8 ± 17.°1. The rotation period of18.1 ± 1.6 d implied by our measurement of vsinI⋆ suggests that the primary has not yet pseudo-synchronized with the binary orbit, but is consistent with gyrochronology and weak tidal interaction with the binary companion. Our result, combined with the known coplanarity of the binary and planet orbits, is suggestive of formation from a single disc. Finally, we considered whether the spectrum of the faint secondary star could affect our measurements. We show through simulations that the effect is negligible for our system, but can lead to strong biases in vsinI⋆ and β for higher flux ratios. We encourage future studies in eclipse spectroscopy test the assumption of a dark secondary for flux ratios ≳1ppt.Publisher PDFPeer reviewe

Case report of right hamate hook fracture in a patient with previous fracture history of left hamate hook: is it hamate bipartite?

BACKGROUND: Hamate hook fracture is a common fracture in golfers and others who play sports that involve rackets or sticks such as tennis or hockey. This patient had a previous hamate fracture in the opposing wrist along with potential features of hamate bipartite. CASE PRESENTATION: A 19 year old male presented with a complaint of right wrist pain on the ulnar side of the wrist with no apparent mechanism of injury. The pain came on gradually one week before being seen in the office and he reported no prior care for the complaint. His history includes traumatic left hamate hook fracture with surgical excision. CONCLUSION: The patient was found to have marked tenderness over the hamate and with a prior fracture to the other wrist, computed tomography of the wrist was ordered revealing a fracture to the hamate hook in the right wrist. He was referred for surgical evaluation and the hook of the hamate was excised. Post-surgically, the patient was able to return to normal activity within eight weeks. This case is indicative of fracture rather than hamate bipartite. This fracture should be considered in a case of ulnar sided wrist pain where marked tenderness is noted over the hamate, especially after participation in club or racket sports

Propositional update operators based on formula/literal dependence

International audienceWe present and study a general family of belief update operators in a propositional setting. Its operators are based on formula/literal dependence, which is more fine-grained than the notion of formula/variable dependence that was proposed in the literature: formula/variable dependence is a particular case of formula/literal dependence. Our update operators are defined according to the "forget-then-conjoin" scheme: updating a belief base by an input formula consists in first forgetting in the base every literal on which the input formula has a negative influence, and then conjoining the resulting base with the input formula. The operators of our family differ by the underlying notion of formula/literal dependence, which may be defined syntactically or semantically, and which may or may not exploit further information like known persistent literals and pre-set dependencies. We argue that this allows to handle the frame problem and the ramification problem in a more appropriate way. We evaluate the update operators of our family w.r.t. two important dimensions: the logical dimension, by checking the status of the Katsuno-Mendelzon postulates for update, and the computational dimension, by identifying the complexity of a number of decision problems (including model checking, consistency and inference), both in the general case and in some restricted cases, as well as by studying compactability issues. It follows that several operators of our family are interesting alternatives to previous belief update operators

Multicenter benchmarking of short and long read wet lab protocols for clinical viral metagenomics

Metagenomics is gradually being implemented for diagnosing infectious diseases. However, in-depth protocol comparisons for viral detection have been limited to individual sets of experimental workflows and laboratories. In this study, we present a benchmark of metagenomics protocols used in clinical diagnostic laboratories initiated by the European Society for Clinical Virology (ESCV) Network on NGS (ENNGS). A mock viral reference panel was designed to mimic low biomass clinical specimens. The panel was used to assess the performance of twelve metagenomic wet lab protocols currently in use in the diagnostic laboratories of participating ENNGS member institutions. Both Illumina and Nanopore, shotgun and targeted capture probe protocols were included. Performance metrics sensitivity, specificity, and quantitative potential were assessed using a central bioinformatics pipeline. Overall, viral pathogens with loads down to 104 copies/ml (corresponding to CT values of 31 in our PCR assays) were detected by all the evaluated metagenomic wet lab protocols. In contrast, lower abundant mixed viruses of CT values of 35 and higher were detected only by a minority of the protocols. Considering the reference panel as the gold standard, optimal thresholds to define a positive result were determined per protocol, based on the horizontal genome coverage. Implementing these thresholds, sensitivity and specificity of the protocols ranged from 67 to 100 % and 87 to 100 %, respectively. A variety of metagenomic protocols are currently in use in clinical diagnostic laboratories. Detection of low abundant viral pathogens and mixed infections remains a challenge, implying the need for standardization of metagenomic analysis for use in clinical settings.</p

Multicenter benchmarking of short and long read wet lab protocols for clinical viral metagenomics

Metagenomics is gradually being implemented for diagnosing infectious diseases. However, in-depth protocol comparisons for viral detection have been limited to individual sets of experimental workflows and laboratories. In this study, we present a benchmark of metagenomics protocols used in clinical diagnostic laboratories initiated by the European Society for Clinical Virology (ESCV) Network on NGS (ENNGS). A mock viral reference panel was designed to mimic low biomass clinical specimens. The panel was used to assess the performance of twelve metagenomic wet lab protocols currently in use in the diagnostic laboratories of participating ENNGS member institutions. Both Illumina and Nanopore, shotgun and targeted capture probe protocols were included. Performance metrics sensitivity, specificity, and quantitative potential were assessed using a central bioinformatics pipeline. Overall, viral pathogens with loads down to 104 copies/ml (corresponding to CT values of 31 in our PCR assays) were detected by all the evaluated metagenomic wet lab protocols. In contrast, lower abundant mixed viruses of CT values of 35 and higher were detected only by a minority of the protocols. Considering the reference panel as the gold standard, optimal thresholds to define a positive result were determined per protocol, based on the horizontal genome coverage. Implementing these thresholds, sensitivity and specificity of the protocols ranged from 67 to 100 % and 87 to 100 %, respectively. A variety of metagenomic protocols are currently in use in clinical diagnostic laboratories. Detection of low abundant viral pathogens and mixed infections remains a challenge, implying the need for standardization of metagenomic analysis for use in clinical settings.</p

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes