Geometric Corroboration of the Earliest Lensed Galaxy at z ≃ 10.8 from Robust Free-form Modelling

A multiply lensed galaxy, MACS0647-JD, with a probable photometric redshift of z ≃ 10.7_(-0.4)^(+0.6) is claimed to constitute one of the very earliest known galaxies, formed well before reionization was completed. However, spectral evidence that MACS0647-JD lies at high redshift has proven infeasible and so here we seek an independent-lensing-based "geometric redshift" derived from the angles between the three lensed images of MACS0647-JD, using our free-form mass model (WSLAP+) for the lensing cluster MACSJ0647.7+7015 (at z = 0.591). Our lens model uses the nine sets of multiple images, including those of MACS0647-JD, identified by the CLASH survey toward this cluster. We convincingly exclude the low-redshift regime of z < 3, for which convoluted critical curves are generated by our method, as the solution bends to accommodate the wide angles of MACS0647-JD for this low redshift. Instead, a best fit to all sets of lensed galaxy positions and redshifts provides a geometric redshift of z≃ 10.8_(-0.4)^(+0.3) for MACS0647-JD, strongly supporting the higher photometric redshift solution. Importantly, we find a tight linear relation between the relative brightnesses of all nine sets of multiply lensed images and their relative magnifications as predicted by our model. This agreement provides a benchmark for the quality of the lens model, and establishes the robustness of our free-form lensing method for measuring model-independent geometric source distances and for deriving objective central cluster mass distributions. After correcting for its magnification the luminosity of MACS0647-JD remains relatively high at M UV = −19.4, which is within a factor of a few in flux of some surprisingly luminous z sime 10–11 candidates discovered recently in Hubble blank field surveys

Geometric Corroboration of the Earliest Lensed Galaxy at z ≃ 10.8 from Robust Free-form Modelling

A multiply lensed galaxy, MACS0647-JD, with a probable photometric redshift of z ≃ 10.7_(-0.4)^(+0.6) is claimed to constitute one of the very earliest known galaxies, formed well before reionization was completed. However, spectral evidence that MACS0647-JD lies at high redshift has proven infeasible and so here we seek an independent-lensing-based "geometric redshift" derived from the angles between the three lensed images of MACS0647-JD, using our free-form mass model (WSLAP+) for the lensing cluster MACSJ0647.7+7015 (at z = 0.591). Our lens model uses the nine sets of multiple images, including those of MACS0647-JD, identified by the CLASH survey toward this cluster. We convincingly exclude the low-redshift regime of z < 3, for which convoluted critical curves are generated by our method, as the solution bends to accommodate the wide angles of MACS0647-JD for this low redshift. Instead, a best fit to all sets of lensed galaxy positions and redshifts provides a geometric redshift of z≃ 10.8_(-0.4)^(+0.3) for MACS0647-JD, strongly supporting the higher photometric redshift solution. Importantly, we find a tight linear relation between the relative brightnesses of all nine sets of multiply lensed images and their relative magnifications as predicted by our model. This agreement provides a benchmark for the quality of the lens model, and establishes the robustness of our free-form lensing method for measuring model-independent geometric source distances and for deriving objective central cluster mass distributions. After correcting for its magnification the luminosity of MACS0647-JD remains relatively high at M UV = −19.4, which is within a factor of a few in flux of some surprisingly luminous z sime 10–11 candidates discovered recently in Hubble blank field surveys

Comparative effectiveness of dipeptidyl peptidase-4 (DPP-4) inhibitors and human glucagon-like peptide-1 (GLP-1) analogue as add-on therapies to sulphonylurea among diabetes patients in the Asia-Pacific region: a systematic review

The prevalence of diabetes mellitus is rising globally, and it induces a substantial public health burden to the healthcare systems. Its optimal control is one of the most significant challenges faced by physicians and policy-makers. Whereas some of the established oral hypoglycaemic drug classes like biguanide, sulphonylureas, thiazolidinediones have been extensively used, the newer agents like dipeptidyl peptidase-4 (DPP-4) inhibitors and the human glucagon-like peptide-1 (GLP-1) analogues have recently emerged as suitable options due to their similar efficacy and favorable side effect profiles. These agents are widely recognized alternatives to the traditional oral hypoglycaemic agents or insulin, especially in conditions where they are contraindicated or unacceptable to patients. Many studies which evaluated their clinical effects, either alone or as add-on agents, were conducted in Western countries. There exist few reviews on their effectiveness in the Asia-Pacific region. The purpose of this systematic review is to address the comparative effectiveness of these new classes of medications as add-on therapies to sulphonylurea drugs among diabetic patients in the Asia-Pacific countries. We conducted a thorough literature search of the MEDLINE and EMBASE from the inception of these databases to August 2013, supplemented by an additional manual search using reference lists from research studies, meta-analyses and review articles as retrieved by the electronic databases. A total of nine randomized controlled trials were identified and described in this article. It was found that DPP-4 inhibitors and GLP-1 analogues were in general effective as add-on therapies to existing sulphonylurea therapies, achieving HbA1c reductions by a magnitude of 0.59–0.90% and 0.77–1.62%, respectively. Few adverse events including hypoglycaemic attacks were reported. Therefore, these two new drug classes represent novel therapies with great potential to be major therapeutic options. Future larger-scale research should be conducted among other Asia-Pacific region to evaluate their efficacy in other ethnic groups

Bench to Bed Evidences for Pharmacokinetic and Pharmacodynamic Interactions Involving Oseltamivir and Chinese Medicine

Oseltamivir (OA), an ethyl ester prodrug of oseltamivir carboxylate (OC), is clinically used as a potent and selective inhibitor of neuraminidase. Chinese medicines have been advocated to combine with conventional drug for avian influenza. The current study aims to investigate the potential pharmacokinetic and pharmacodynamic interactions of a Chinese medicine formula, namely, Yin Qiao San and Sang Ju Yin (CMF1), commonly used for anti-influenza in combination with OA in both rat and human, and to reveal the underlined mechanisms. It was found that although Cmax, AUC and urinary recovery of OC, as well as metabolic ratio (AUCOC/AUCOA), were significantly decreased in a dose-dependent manner following combination use of CMF1 and OA in rat studies (P<0.01), such coadministration in 14 healthy volunteers only resulted in a trend of minor decrease in the related parameters. Further mechanistic studies found that although CMF1 could reduce absorption and metabolism of OA, it appears to enhance viral inhibition of OA (P<0.01). In summary, although there was potential interaction between OA and CMF1 found in rat studies, its clinical impact was expected to be minimal. The coadministration of OA and CMF1 at the clinical recommended dosages is, therefore, considered to be safe

Predictors of Patient Satisfaction in Spine Surgery: A Systematic Review

Background: Recently, there has been increased interest in patient satisfaction measures such as Press Ganey and Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys. In this systematic review, the spine surgery literature is analyzed to evaluate factors predictive of patient satisfaction as measured by these surveys. Methods: A thorough literature search was performed in PubMed/MEDLINE, Google Scholar, and Cochrane databases. All English-language articles from database inception to July 2020 were screened for study inclusion according to PRISMA guidelines. Results: Twenty-four of the 1899 published studies were included for qualitative analysis. There has been a statistically significant increase in the number of publications across years (P = 0.04). Overall, the studies evaluated the relationship between patient satisfaction and patient demographics (71%), preoperative and intraoperative clinical factors (21%), and postoperative factors (33%). Top positive predictors of patient satisfaction were patient and nursing/medical staff relationship (n = 4; 17%), physician–patient relationship (n = 4; 17%), managerial oversight of received care (n = 3; 13%), same sex/ethnicity between patient and physician (n = 2; 8%), and older age (n = 2; 8%). Top negative predictors of patient satisfaction were high Charlson Comorbidity Index/high disability/worse overall health functioning (n = 7; 29%), increased length of hospital stay (n = 4; 17%), high rating for pain/complications/readmissions (n = 4; 17%), and psychosocial factors (n = 3; 13%). Conclusions: There is heterogeneity in terms of different factors, both clinical and nonclinically related, that affect patient satisfaction ratings. More research is warranted to investigate the role of hospital consumer surveys in the spine surgical patient population

The effectiveness of dietary approaches to stop hypertension (DASH) counselling on estimated 10-year cardiovascular risk among patients with newly diagnosed grade 1 hypertension : a randomised clinical trial

The Dietary Approaches to Stop Hypertension (DASH) has been shown to lower blood pressure in the West. However, the real-life impact of DASH on reducing cardiovascular (CV) risk in routine clinical setting has not been studied. Methods A parallel-group, open-labelled, physician-blinded, randomised controlled trial was conducted in January–June 2013 and followed up for 6- and 12-months in primary care settings in Hong Kong. Patients newly diagnosed with grade 1 hypertension (aged 40–70 years) who had no concomitant medical conditions requiring dietary modifications were consecutively recruited. Subjects were randomised to standard education (usual care) (n = 275), or usual care plus dietitian-delivered DASH-based dietary counselling in a single one-to-one session (intervention) (n = 281). Primary outcomes were the changes in estimated 10-year CV risk. Results Outcome data were available for 504 (90.6%) and 485 (87.2%) patients at 6 and 12 months, respectively. There was no difference in the reduction of 10-year CV risk between the two groups at 6 months (−0.13%, 95% confidence interval [95% CI] −0.50% to 0.23%, p = 0.477) and 12 months (−0.08%, 95% CI −0.33% to 0.18%, p = 0.568). Multivariate regression analyses showed that male subjects, younger patients, current smokers, subjects with lower educational level, and those who dined out for main meals for ≥4 times in a typical week were significantly associated with no improvements in CV risk. Conclusions The findings may not support automatic referral of newly diagnosed grade 1 hypertensive patients for further one-to-one dietitian counselling on top of primary care physician's usual care. Patients with those risk factors identified should receive more clinical attention to reduce their CV risk

A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate

Serine is a both a proteinogenic amino acid and the source of one-carbon units essential for de novo purine and deoxythymidine synthesis. In the canonical glucose-derived serine synthesis pathway, Homo sapiens phosphoglycerate dehydrogenase (PHGDH) catalyzes the first, ratelimiting step. Genetic loss of PHGDH is toxic towards PHGDH-overexpressing breast cancer cell lines even in the presence of exogenous serine. Here, we use a quantitative high-throughput screen to identify small molecule PHGDH inhibitors. These compounds reduce the production of glucose-derived serine in cells and suppress the growth of PHGDH-dependent cancer cells in culture and in orthotopic xenograft tumors. Surprisingly, PHGDH inhibition reduced the incorporation into nucleotides of one-carbon units from glucose-derived and exogenous serine. We conclude that glycolytic serine synthesis coordinates the use of one-carbon units from endogenous and exogenous serine in nucleotide synthesis, and suggest that one-carbon unit wasting may contribute to the efficacy of PHGDH inhibitors in vitro and in vivo.Damon Runyon Cancer Research Foundation (Sally Gordon Fellowship DRG-112-12)United States. Dept. of Defense. Breast Cancer Research Program (Postdoctoral Fellowship BC120208)American Society for Radiation Oncology (Resident Seed Grant RA-2011-1)European Molecular Biology Organization (Long-Term Fellowship)National Institutes of Health (U.S.) (R03 DA034602-01A1, R01 CA129105, R01 CA103866, and R37 AI047389)United States. Department of Defense (W81XWH-14-PRCRP-IA)Alexander and Margaret Stewart Trus

Does nasal surgery improve multilevel surgical outcome in obstructive sleep apnea:A multicenter study on 735 patients

Objective Does nasal surgery affect multilevel surgical success outcome. Methods Prospective eight country nonrandomized trial of 735 obstructive sleep apnea (OSA) patients, who had multilevel palate and/or tongue surgery, divided into two groups, with or without nose surgery. Results There were 575 patients in nose group, 160 patients in no nose group. The mean age for nose group 44.6 ± 11.4, no nose group 44.2 ± 11.8. Mean preoperative BMI for nose group 27.5 ± 3.6, no nose group 27.5 ± 4.1, mean postoperative BMI nose group 26.3 ± 3.7, no nose group 27.1 ± 3.8 (P = .006). Mean preoperative AHI nose group 32.7 ± 19.4, no nose group 34.3 ± 25.0 (P = .377); and mean postoperative AHI nose group 13.5 ± 10.2, no nose group 17.1 ± 16.0 (P = .001). Mean preoperative ESS nose group was 11.3 ± 4.7, no nose group was 10.4 ± 5.4 (P = .051); and mean postoperative ESS nose group was 5.3 ± 3.2, no nose group was 6.7 ± 2.8 (P = .001). The nose group had higher percentage change (adjusted for age, gender, BMI) in AHI (33.7%, 95% CI 14% to 53.5%) compared to the no nose group (P = .001); the nose group also had more percentage change in ESS (37%, 95% CI 23.6% to 50.3%) compared to the no nose group (P < .001). Change in BMI did not affect AHI nor ESS change (Cohen effect 0.03 and 0.14, respectively). AHI change in both groups were also statistically significant in the mild OSA (P = .008) and the severe OSA (P = .01). Success rate of surgery for the nose group 68.2%, while the no nose group 55.0% (P = .002). Conclusion Combining nose surgery in multilevel surgery improves surgical success. Level of evidence IIC

Face-selective electrostatic control of hydrothermal zinc oxide nanowire synthesis

Rational control over the morphology and the functional properties of inorganic nanostructures has been a long-standing goal in the development of bottom-up device fabrication processes. We report that the geometry of hydrothermally grown zinc oxide nanowires can be tuned from platelets to needles, covering more than three orders of magnitude in aspect ratio (~0.1–100). We introduce a classical thermodynamics-based model to explain the underlying growth inhibition mechanism by means of the competitive and face-selective electrostatic adsorption of non-zinc complex ions at alkaline conditions. The performance of these nanowires rivals that of vapour-phase-grown nanostructures and their low-temperature synthesis (<60 °C) is favourable to the integration and in situ fabrication of complex and polymer-supported devices. We illustrate this capability by fabricating an all-inorganic light-emitting diode in a polymeric microfluidic manifold. Our findings indicate that electrostatic interactions in aqueous crystal growth may be systematically manipulated to synthesize nanostructures and devices with enhanced structural control.National Science Foundation (U.S.) (MIT Center for Bits and Atoms (NSF CCR0122419))Massachusetts Institute of Technology. Media LaboratoryKorea Foundation for Advanced StudiesSamsung Electronics Co. (research internship)Harvard University. Society of FellowsWallace H. Coulter Foundation (Early Career Award)Brain & Behavior Research Foundation (Young Investigator Award)National Science Foundation (U.S.)National Institutes of Health (U.S.) (Director’s New Innovator Award

Cardiac and vascular structure and function parameters do not improve with alternate nightly home hemodialysis: An interventional cohort study

Background: Nightly extended hours hemodialysis may improve left ventricular hypertrophy and function and endothelial function but presents problems of sustainability and increased cost. The effect of alternate nightly home hemodialysis (NHD) on cardiovascular structure and function is not known