Metformin Dosis Rendah Jangka Pendek dan Risiko Timbulnya Aterosklerosis pada Prediabetes Non Obes

Low-dose short-term metformin and the risk of atherosclerosis in non obese prediabetic.Background: The establishment of macrovascular (cardiovascular) event is initiated in the period of prediabetic. Metformin plays role in the carbohydrate and lipid metabolism as well as vascular protection. The mechanism of the cardiovascular event risk increase in the prediabetic individual has not been clearly established. The study was to determine if insulin resistance control by low-dose short-term metformin administration in the non-obese prediabetic individual might decrease the atherosclerosis risk.Method: The present study was a prospective, experimental study with pretest-posttest control group design. It was conducted on the first degree relative of type-2 DM patient who met the criteria of non-obese prediabetic individual. Subjects were randomly classified into treatment group (designed for metformin administration), and the control group (designed for placebo administration). The prediction of atherosclerosis risk was based on the hsCRP, PAI-1, VCAM-1 and fibrinogen levels.Results: The margin between pre and post metformin administration term were 1.89 vs 0.06 mg/L (p=0.001), 1.42 vs 0.84 IU/mL (p=0.015), 180.85 vs 03.81 mg/L (p=0.061) and 80.15 vs 31.42 mg/dL (p=0.001) for hsCRP, PAI-1, VCAM-1 and Fibrinogen in the treatment and control group, respectively.Conclusion: Low-dose short-term metformin administration might decrease the atherosclerosis risk factor in the non-obese prediabetic individuals

Kontribusi Lubang Angin dan Ventilasi Udara pada Bangunan Sobokartti Semarang dalam Mewujudkan Kenyamanan Termal

Di Kota Semarang terdapat beberapa bangunan yang berfungsi sebagai pertunjukan kesenian peninggalan penjajahan Belanda yang sudah ditetapkan sebagai bangunan cagar budaya dengan menggunakan ventilasi udara alami melalui lubang angin pada atap dan kisi-kisi jendela di dalam ruangan dari awal pembangunan tahun 1930 sampai sekarang, bangunan kesenian di Jl. Dr. Cipto yang diberi nama Volkstheater Sobokartti yang kini dikenal dengan nama Sobokartti karya Thomas Karsten. Metode penelitian ini menggunakan metode pengukuran langsung di lokasi lapangan dan menggunakan responden. Pelaksanaan pengukuran dilakukan selama 17 jam, masing-masing dilakukan dalam 1 jam sekali. Variabel yang diukur adalah suhu udara, kelembaban udara, pergerakan udara untuk memberikan kontribusi dalam mewujudkan Kenyamanan termal. Yang sementara itu nilai temperatur efektif dijadikan dasar dalam menentukan Kenyamanan termal pada bangunan Sobokartti. Hasil penelitian menunjukkan bahwa keberadaan lubang angin pada atap dan kisi – kisi jendela pada bangunan dapat berpengaruh pada kondisi Kenyamanan termal, terutama area dalam bangunan. Kesimpulan dari penelitian ini adalah kondisi didalam gedung tetap nyaman karena ventilasi udara di dalam gedung tetap terjaga dan berkecukupan dengan mengandalkan lubang angin pada atap dan kisi-kisi jendela

Classification of stratospheric extreme events according to their downward propagation to the troposphere

Abstract This study presents a classification of stratospheric extreme events during northern winter into events with or without a consistent downward propagation of anomalies to the troposphere. Anomalous strong and weak stratospheric polar vortex events are detected from daily time series of the polar cap averaged (60°–90°N) geopotential height anomaly. The method is applied to chemistry‐climate model data (E39CA and WACCM3.5) and reanalyses data (ERA40). The analyses show that in about 80% of all events no significant tropospheric response can be detected. The stratospheric perturbation of both weak and strong events with a significant tropospheric response persists significantly longer throughout the stratosphere compared to the events without a tropospheric response. The strength of the stratospheric perturbation determines the strength of the tropospheric response only to a small degree. Results are consistent across all three data sets

A comparative framework: how broadly applicable is a 'rigorous' critical junctures framework?

The paper tests Hogan and Doyle's (2007, 2008) framework for examining critical junctures. This framework sought to incorporate the concept of ideational change in understanding critical junctures. Until its development, frameworks utilized in identifying critical junctures were subjective, seeking only to identify crisis, and subsequent policy changes, arguing that one invariably led to the other, as both occurred around the same time. Hogan and Doyle (2007, 2008) hypothesized ideational change as an intermediating variable in their framework, determining if, and when, a crisis leads to radical policy change. Here we test this framework on cases similar to, but different from, those employed in developing the exemplar. This will enable us determine whether the framework's relegation of ideational change to a condition of crisis holds, or, if ideational change has more importance than is ascribed to it by this framework. This will also enable us determined if the framework itself is robust, and fit for the purposes it was designed to perform — identifying the nature of policy change

Multimodel climate and variability of the stratosphere

The stratospheric climate and variability from simulations of sixteen chemistryclimate models is evaluated. On average the polar night jet is well reproduced though its variability is less well reproduced with a large spread between models. Polar temperature biases are less than 5 K except in the Southern Hemisphere (SH) lower stratosphere in spring. The accumulated area of low temperatures responsible for polar stratospheric cloud formation is accurately reproduced for the Antarctic but underestimated for the Arctic. The shape and position of the polar vortex is well simulated, as is the tropical upwelling in the lower stratosphere. There is a wide model spread in the frequency of major sudden stratospheric warnings (SSWs), late biases in the breakup of the SH vortex, and a weak annual cycle in the zonal wind in the tropical upper stratosphere. Quantitatively, �metrics� indicate a wide spread in model performance for most diagnostics with systematic biases in many, and poorer performance in the SH than in the Northern Hemisphere (NH). Correlations were found in the SH between errors in the final warming, polar temperatures, the leading mode of variability, and jet strength, and in the NH between errors in polar temperatures, frequency of major SSWs, and jet strength. Models with a stronger QBO have stronger tropical upwelling and a colder NH vortex. Both the qualitative and quantitative analysis indicate a number of common and long�standing model problems, particularly related to the simulation of the SH and stratospheric variability

Northern winter climate change: assessment of uncertainty in CMIP5 projections related to stratosphere-troposphere coupling

Journal ArticlePublished versionFuture changes in the stratospheric circulation could have an important impact on northern winter tropospheric climate change, given that sea level pressure (SLP) responds not only to tropospheric circulation variations but also to vertically coherent variations in troposphere-stratosphere circulation. Here we assess northern winter stratospheric change and its potential to influence surface climate change in the Coupled Model Intercomparison Project-Phase 5 (CMIP5) multimodel ensemble. In the stratosphere at high latitudes, an easterly change in zonally averaged zonal wind is found for the majority of the CMIP5 models, under the Representative Concentration Pathway 8.5 scenario. Comparable results are also found in the 1% CO2 increase per year projections, indicating that the stratospheric easterly change is common feature in future climate projections. This stratospheric wind change, however, shows a signi fi cant spread among the models. By using linear regression, we quantify the impact of tropical upper troposphere warming, polar amplification, and the stratospheric wind change on SLP. We find that the intermodel spread in stratospheric wind change contributes substantially to the intermodel spread in Arctic SLP change. The role of the stratosphere in determining part of the spread in SLP change is supported by the fact that the SLP change lags the stratospheric zonally averaged wind change. Taken together, these findings provide further support for the importance of simulating the coupling between the stratosphere and the troposphere, to narrow the uncertainty in the future projection of tropospheric circulation changes

The complex behavior of El Niño winter 2015-2016

This paper examines the outstanding characteristics of the strong 2015-2016 El Nino (EN) winter and its impact over the European region through the stratosphere. Despite being classified as a strong eastern Pacific (EP) EN event, our analysis reveals an anomalous behavior, with some signatures that are more typical of central Pacific (CP) EN events instead. They include (i) a record-breaking value of the CP index, (ii) a stronger polar vortex in early and midwinter, due to reduced upward wave activity and a weakened Aleutian low, and (iii) the occurrence of one of the earliest stratospheric final warmings (SFWs) on record, which are more prone to occur during CP-EN. Following the SFW, a stratospheric influence on the Euro-Atlantic sector is reported in spring, with persistent Greenland blocking resulting in extreme precipitation over some southern European regions. Results highlight the importance of considering early SFWs as mediators of El Nino teleconnections

RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord

ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned \u3e50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of differentially expressed genes (DEG’s). Ingenuity Pathways Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF) found to be a major pathway regulator (IPA) and TNFα-induced protein 2 (TNFAIP2) as a major network “hub” gene (WGCNA). Using the oPOSSUM algorithm, we analyzed transcription factors (TF) controlling expression of the nine DEG/hub genes in the ALS samples and identified TF’s involved in inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms) reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be helpful in ALS patients

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen