Seasonal variations in water quality and major threats to Ramsagar reservoir, India

Ramsagar reservoir, a small inland reservoir located in Datia district, Madhya Pradesh is constructed over Nichroli nallah, in the basin of Sindh River. The physico-chemical characteristics, trophic status and pollution studies of Ramsagar reservoir have been studied from April, 2003 to March, 2005. The nutrients including silicates (0.65 - 8.42 mgl-1), sulphates (1.50 - 8.87 mgl-1), phosphates (0.013 - 0.054 mgl-1), nitrates (0.011 - 0.033 mgl-1) and potassium (1.97 - 4.86 mgl-1) are in sufficient quantities for the growth of aquatic animals in the reservoir. The above study indicated that the Ramsagar reservoir is under the category of mesotrophic water body slightly inclined towards eutrophication. Therefore, the conservation and management of this water body is very much required

Antiarrhythmic Medication for Atrial Fibrillation (AIM-AF) study: A physician survey of sotalol use and patient monitoring in the EU and USA

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Sanofi Introduction In the recent 2020 European Society of Cardiology (ESC) guidelines, sotalol was downgraded from a Class IA to a llbA recommendation and advised not to be prescribed in patients with specific co-morbidities. All patients given sotalol should also be closely monitored for proarrhythmic risk factors. To date, American guidelines have not changed. Our study sought to understand the use of sotalol in AF patients and monitoring compliance across the USA and in the EU, with regards to the recent ESC guideline change. Method An online physician survey of cardiologists, cardiac electrophysiologists (EPs) and interventional EPs (N = 569) was conducted in the USA, Germany, Italy and the UK. All respondents were actively treating ≥10 AF patients who received drug therapy and/or who had received or were referred for ablation. This survey included topics on AF types and antiarrhythmic drug (AAD) treatment practices in those with AF +/- co-morbidities (including left ventricular hypertrophy [LVH], LV heart failure, and sinus node dysfunction or renal impairment). Results Sotalol was prescribed across all patient sub-groups, with high use in those with hypertension (49% of physicians) and revascularised coronary artery disease (44%). Sotalol use was consistently higher among US respondents than EU clinicians across co-morbidity categories (heart failure with reduced ejection fraction: 25% vs 14% [guideline deviation]; hypertension: 53% vs 44%; valve disease: 33% vs 23%; recent myocardial infarction [MI]: 44% vs 22%; old MI: 52% vs 31%, respectively). Use was also generally higher among EPs compared with cardiologists, but remained low in patients with minimal or no structural heart disease across all groups. Many respondents prescribed sotalol in those with LVH (35%) or renal impairment (22%), despite guidelines advising against this due to proarrhythmia risk. This contrasts with expressed respondent concerns, as 43% cited ventricular proarrythmia risk as a reason for not using sotalol. Although respondents noted concern over such risks, as per the new guidelines, routine monitoring for these factors was not performed as follows: electrocardiograms (ECG) (19% [US: 23%; EU: 15%]), renal function assessment (42% [US: 36%; EU: 50%]) or electrolyte monitoring (48% [US: 49%; EU: 46%]). Respondents reported sotalol is typically initiated in hospital (45% of patients) or in outpatients with intensive ECG monitoring (37%), but is also being started in non-monitored outpatients (19%). Conclusions Although sotalol use among EU clinicians was lower compared with the USA, which may reflect recent ESC guideline changes, the extent of monitoring practices that would indicate avoidance in those with proarrhythmic risk factors was insufficient. The lack of routine monitoring for specific factors, such as renal impairment or electrolytes, and unmonitored outpatient initiation highlights an ongoing need for further education on maximising safety when using AADs. Abstract Figure

Parameterized Verification of Safety Properties in Ad Hoc Network Protocols

We summarize the main results proved in recent work on the parameterized verification of safety properties for ad hoc network protocols. We consider a model in which the communication topology of a network is represented as a graph. Nodes represent states of individual processes. Adjacent nodes represent single-hop neighbors. Processes are finite state automata that communicate via selective broadcast messages. Reception of a broadcast is restricted to single-hop neighbors. For this model we consider a decision problem that can be expressed as the verification of the existence of an initial topology in which the execution of the protocol can lead to a configuration with at least one node in a certain state. The decision problem is parametric both on the size and on the form of the communication topology of the initial configurations. We draw a complete picture of the decidability and complexity boundaries of this problem according to various assumptions on the possible topologies.Comment: In Proceedings PACO 2011, arXiv:1108.145

Real-world utilization of the pill-in-the-pocket method for terminating episodes of atrial fibrillation: data from the multinational Antiarrhythmic Interventions for Managing Atrial Fibrillation (AIM-AF) survey

AIMS: Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. Episodes may stop spontaneously (paroxysmal AF); may terminate only via intervention (persistent AF); or may persist indefinitely (permanent AF) (see European and American guidelines, referenced below, for more precise definitions). Recently, there has been renewed interest in an approach to terminate AF acutely referred to as 'pill-in-the-pocket' (PITP). The PITP is recognized in both the US and European guidelines as an effective option using an oral antiarrhythmic drug for acute conversion of acute/recent-onset AF. However, how PITP is currently used has not been systematically evaluated. METHODS AND RESULTS: The recently published Antiarrhythmic Interventions for Managing Atrial Fibrillation (AIM-AF) survey included questions regarding current PITP usage, stratified by US vs. European countries surveyed, by representative countries within Europe, and by cardiologists vs. electrophysiologists. This manuscript presents the data from this planned sub-study. Our survey revealed that clinicians in both the USA and Europe consider PITP in about a quarter of their patients, mostly for recent-onset AF with minimal or no structural heart disease (guideline appropriate). However, significant deviations exist. See the Graphical abstract for a summary of the data. CONCLUSION: Our findings highlight the frequent use of PITP and the need for further physician education about appropriate and optimal use of this strategy

Real-world utilization of the pill-in-the-pocket method for terminating episodes of atrial fibrillation: data from the multinational Antiarrhythmic Interventions for Managing Atrial Fibrillation (AIM-AF) survey.

AIMS: Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. Episodes may stop spontaneously (paroxysmal AF); may terminate only via intervention (persistent AF); or may persist indefinitely (permanent AF) (see European and American guidelines, referenced below, for more precise definitions). Recently, there has been renewed interest in an approach to terminate AF acutely referred to as 'pill-in-the-pocket' (PITP). The PITP is recognized in both the US and European guidelines as an effective option using an oral antiarrhythmic drug for acute conversion of acute/recent-onset AF. However, how PITP is currently used has not been systematically evaluated. METHODS AND RESULTS: The recently published Antiarrhythmic Interventions for Managing Atrial Fibrillation (AIM-AF) survey included questions regarding current PITP usage, stratified by US vs. European countries surveyed, by representative countries within Europe, and by cardiologists vs. electrophysiologists. This manuscript presents the data from this planned sub-study. Our survey revealed that clinicians in both the USA and Europe consider PITP in about a quarter of their patients, mostly for recent-onset AF with minimal or no structural heart disease (guideline appropriate). However, significant deviations exist. See the Graphical abstract for a summary of the data. CONCLUSION: Our findings highlight the frequent use of PITP and the need for further physician education about appropriate and optimal use of this strategy

AIM-AF: A Physician Survey in the United States and Europe.

Background Guideline recommendations are the accepted reference for selection of therapies for rhythm control of atrial fibrillation (AF). This study was designed to understand physicians' treatment practices and adherence to guidelines. Methods and Results The AIM-AF (Antiarrhythmic Medication for Atrial Fibrillation) study was an online survey of clinical cardiologists and electrophysiologists that was conducted in the United States and Europe (N=629). Respondents actively treated ≥30 patients with AF who received drug therapy, and had received or were referred for ablation every 3 months. The survey comprised 96 questions on physician demographics, AF types, and treatment practices. Overall, 54% of respondents considered guidelines to be the most important nonpatient factor influencing treatment choice. Across most queried comorbidities, amiodarone was selected by 60% to 80% of respondents. Other nonadherent usage included sotalol by 21% in patients with renal impairment; dofetilide initiation (16%, United States only) outside of hospital; class Ic agents by 6% in coronary artery disease; and dronedarone by 8% in patients with heart failure with reduced ejection fraction. Additionally, rhythm control strategies were frequently chosen in asymptomatic AF (antiarrhythmic drugs [AADs], 35%; ablation, 8%) and subclinical AF (AADs, 38%; ablation, 13%). Despite guideline algorithms emphasizing safety first, efficacy (48%) was selected as the most important consideration for AAD choice, followed by safety (34%). Conclusions Despite surveyed clinicians recognizing the importance of guidelines, nonadherence was frequently observed. While deviation may be reasonable in selected patients, in general, nonadherence has the potential to compromise patient safety. These findings highlight an underappreciation of the safe use of AADs, emphasizing the need for interventions to support optimal AAD selection

Gastrointestinal adenocarcinomas of the esophagus, stomach, and colon exhibit distinct patterns of genome instability and oncogenesis

A more detailed understanding of the somatic genetic events that drive gastrointestinal adenocarcinomas is necessary to improve diagnosis and therapy. Using data from high-density genomic profiling arrays, we conducted an analysis of somatic copy-number aberrations in 486 gastrointestinal adenocarcinomas including 296 esophageal and gastric cancers. Focal amplifications were substantially more prevalent in gastric/esophageal adenocarcinomas than colorectal tumors. We identified 64 regions of significant recurrent amplification and deletion, some shared and others unique to the adenocarcinoma types examined. Amplified genes were noted in 37% of gastric/esophageal tumors, including in therapeutically targetable kinases such as ERBB2, FGFR1, FGFR2, EGFR, and MET, suggesting the potential use of genomic amplifications as biomarkers to guide therapy of gastric and esophageal cancers where targeted therapeutics have been less developed compared with colorectal cancers. Amplified loci implicated genes with known involvement in carcinogenesis but also pointed to regions harboring potentially novel cancer genes, including a recurrent deletion found in 15% of esophageal tumors where the Runt transcription factor subunit RUNX1 was implicated, including by functional experiments in tissue culture. Together, our results defined genomic features that were common and distinct to various gut-derived adenocarcinomas, potentially informing novel opportunities for targeted therapeutic interventions

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy.

We performed massively parallel sequencing of paired tumor/normal samples from 203 multiple myeloma (MM) patients and identified significantly mutated genes and copy number alterations and discovered putative tumor suppressor genes by determining homozygous deletions and loss of heterozygosity. We observed frequent mutations in KRAS (particularly in previously treated patients), NRAS, BRAF, FAM46C, TP53, and DIS3 (particularly in nonhyperdiploid MM). Mutations were often present in subclonal populations, and multiple mutations within the same pathway (e.g., KRAS, NRAS, and BRAF) were observed in the same patient. In vitro modeling predicts only partial treatment efficacy of targeting subclonal mutations, and even growth promotion of nonmutated subclones in some cases. These results emphasize the importance of heterogeneity analysis for treatment decisions