What eddy-covariance measurements tell us about prior land flux errors in CO2-flux inversion schemes

0.2 after 200 km). Separating out the plant functional types did not increase the spatial correlations, except for the deciduous broad-leaved forests. Using the statistics of the flux measurements as a proxy for the statistics of the prior flux errors was shown not to be a viable approach. A statistical model allowed us to upscale the site-level flux error statistics to the coarser spatial and temporal resolutions used in regional or global models. This approach allowed us to quantify how aggregation reduces error variances, while increasing correlations. As an example, for a typical inversion of grid point (300 km × 300 km) monthly fluxes, we found that the prior flux error follows an approximate e-folding correlation length of 500 km only, with correlations from one month to the next as large as 0.6

The role of multiple marks in epigenetic silencing and the emergence of a stable bivalent chromatin state

We introduce and analyze a minimal model of epigenetic silencing in budding yeast, built upon known biomolecular interactions in the system. Doing so, we identify the epigenetic marks essential for the bistability of epigenetic states. The model explicitly incorporates two key chromatin marks, namely H4K16 acetylation and H3K79 methylation, and explores whether the presence of multiple marks lead to a qualitatively different systems behavior. We find that having both modifications is important for the robustness of epigenetic silencing. Besides the silenced and transcriptionally active fate of chromatin, our model leads to a novel state with bivalent (i.e., both active and silencing) marks under certain perturbations (knock-out mutations, inhibition or enhancement of enzymatic activity). The bivalent state appears under several perturbations and is shown to result in patchy silencing. We also show that the titration effect, owing to a limited supply of silencing proteins, can result in counter-intuitive responses. The design principles of the silencing system is systematically investigated and disparate experimental observations are assessed within a single theoretical framework. Specifically, we discuss the behavior of Sir protein recruitment, spreading and stability of silenced regions in commonly-studied mutants (e.g., sas2, dot1) illuminating the controversial role of Dot1 in the systems biology of yeast silencing.Comment: Supplementary Material, 14 page

Comparing the effect of STan (cardiotocographic electronic fetal monitoring (CTG) plus analysis of the ST segment of the fetal electrocardiogram) with CTG alone on emergency caesarean section rates: study protocol for the STan Australian Randomised controlled Trial (START).

BACKGROUND: Cardiotocography is almost ubiquitous in its use in intrapartum care. Although it has been demonstrated that there is some benefit from continuous intrapartum fetal monitoring using cardiotocography, there is also an increased risk of caesarean section which is accompanied by short-term and long-term risks to the mother and child. There is considerable potential to reduce unnecessary operative delivery with up to a 60% false positive diagnosis of fetal distress using cardiotocography alone. ST analysis of the fetal electrocardiogram is a promising adjunct to cardiotocography alone, and permits detection of metabolic acidosis of the fetus, potentially reducing false positive diagnosis of fetal distress. METHODS: This study will be a single-centre, parallel-group, randomised controlled trial, conducted over 3 years. The primary hypothesis will be that the proportion of women with an emergency caesarean section on ST analysis will not equal that for women on cardiotocography monitoring alone. Participants will be recruited at the Women's and Children's Hospital, a high-risk specialty facility with approximately 5000 deliveries per annum. A total of 1818 women will be randomised to the treatment or conventional arm with an allocation ratio of 1:1, stratified by parity. The primary outcome is emergency caesarean section (yes/no). Statistical analysis will follow standard methods for randomised trials and will be performed on an intention-to-treat basis. Secondary maternal and neonatal outcomes will also be analysed. Additional study outcomes include psychosocial outcomes, patient preferences and cost-effectiveness. DISCUSSION: Approximately 20% of Australian babies are delivered by emergency caesarean section. This will be the first Australian trial to examine ST analysis of the fetal electrocardiogram as an adjunct to cardiotocography as a potential method for reducing this proportion. The trial will be among the first to comprehensively examine ST analysis, taking into account the impact on psychosocial well-being as well as cost-effectiveness. This research will provide Australian evidence for clinical practice and guideline development as well as for policy-makers and consumers to make informed, evidence-based choices about care in labour. TRIAL REGISTRATION: ANZCTR, ACTRN1261800006268 . Registered on 19 January 2018

Identification and validation of differentially expressed genes for targeted therapy in NSCLC using integrated bioinformatics analysis

BackgroundDespite the high prevalence of lung cancer, with a five-year survival rate of only 23%, the underlying molecular mechanisms of non-small cell lung cancer (NSCLC) remain unknown. There is a great need to identify reliable candidate biomarker genes for early diagnosis and targeted therapeutic strategies to prevent cancer progression.MethodsIn this study, four datasets obtained from the Gene Expression Omnibus were evaluated for NSCLC- associated differentially expressed genes (DEGs) using bioinformatics analysis. About 10 common significant DEGs were shortlisted based on their p-value and FDR (DOCK4, ID2, SASH1, NPR1, GJA4, TBX2, CD24, HBEGF, GATA3, and DDR1). The expression of significant genes was validated using experimental data obtained from TCGA and the Human Protein Atlas database. The human proteomic data for post- translational modifications was used to interpret the mutations in these genes.ResultsValidation of DEGs revealed a significant difference in the expression of hub genes in normal and tumor tissues. Mutation analysis revealed 22.69%, 48.95%, and 47.21% sequence predicted disordered regions of DOCK4, GJA4, and HBEGF, respectively. The gene-gene and drug-gene network analysis revealed important interactions between genes and chemicals suggesting they could act as probable drug targets. The system-level network showed important interactions between these genes, and the drug interaction network showed that these genes are affected by several types of chemicals that could serve as potential drug targets.ConclusionsThe study demonstrates the importance of systemic genetics in identifying potential drug- targeted therapies for NSCLC. The integrative system- level approach should contribute to a better understanding of disease etiology and may accelerate drug discovery for many cancer types

A Low Power Multi-Class Migraine Detection Processor Based on Somatosensory Evoked Potentials

Migraine is a disabling neurological disorder that can be recurrent and persist for long durations. The continuous monitoring of the brain activities can enable the patient to respond on time before the occurrence of the approaching migraine episode to minimize the severity. Therefore, there is a need for a wearable device that can ensure the early diagnosis of a migraine attack. This brief presents a low latency, and power-efficient feature extraction and classification processor for the early detection of a migraine attack. Somatosensory Evoked Potentials (SEP) are utilized to monitor the migraine patterns in an ambulatory environment aiming to have a processor integrated on-sensor for power-efficient and timely intervention. In this work, a complete digital design of the wearable environment is proposed. It allows the extraction of multiple features including multiple power spectral bands using 256-point fast Fourier transform (FFT), root mean square of late HFO bursts and latency of N20 peak. These features are then classified using a multi-classification artificial neural network (ANN)-based classifier which is also realized on the chip. The proposed processor is placed and routed in a 180nm CMOS with an active area of 0.5mm(2). The total power consumption is 249 mu W while operating at a 20MHz clock with full computations completed in 1.31ms

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Volvulus as a complication of chronic intestinal pseudo-obstruction syndrome

Chronic intestinal pseudo-obstruction syndrome (CIPS) is a severe motility disorder of the gastrointestinal tract that presents with continuous or recurrent symptoms and signs of intestinal obstruction without evidence of a structural lesion occluding the intestinal lumen. Mechanical obstruction might occur in these patients as well but is typically difficult to distinguish from an exacerbation of CIPS. We report two pediatric cases in which mechanical obstruction by volvulus mimicked an exacerbation of CIPS, requiring surgical intervention. Conclusion: Awareness of the possibility of true mechanical obstruction in CIPS patients during an exacerbation episode is needed, as this is a severe condition and usually requires surgical intervention

HIV-1 subtype A infection in a community of intravenous drug users in Pakistan

BACKGROUND: Data on the subtypes of HIV in a population help in predicting the potential foci of epidemic, tracking the routes of infection and following the patterns of the virus' genetic divergence. Globally, the most prevalent HIV infection is the HIV-1 subtype C. In Asia, predominant subtypes of HIV-1 are B, C, and CRF-01AE. During the last few years, HIV prevalence in Pakistan has taken the form of a concentrated epidemic in at least two high risk groups, namely, Intravenous Drug Users (IDUs) and Male Sex Workers (MSWs). Factors that have facilitated the proliferation of HIV infection include transmission through a large number of repatriates and needle-sharing intravenous drug users, unscreened blood transfusions, and sexual illiteracy. The HIV subtypes infecting Pakistani populations have not been explored to date. In this study, we analyzed HIV-1 subtypes from in a high-risk community of IDUs in Karachi, the largest city of Pakistan. METHODS: Samples were collected from 34 IDUs after their informed consent. In addition, the study subjects were administered a questionnaire regarding their sexual behavior and travel history. For HIV analysis, DNA was extracted from the samples and analyzed for HIV types and subtypes using subtype-specific primers in a nested polymerase chain reaction (PCR). The results from this PCR were further confirmed using the Heteroduplex Mobility Assay (HMA). RESULTS: We found HIV-1 subtype A in all the 34 samples analyzed. A few of the study subjects were found to have a history of travel and stay in the United Arab Emirates. The same subjects also admitted to having contact with commercial sex workers during their stay abroad. CONCLUSION: Our study therefore shows clade A HIV-1 to be prevalent among the IDUs in Karachi. As the prevalence of HIV in Pakistan continues to rise, more work needs to be done to track the infection, and to analyze the strains of HIV spreading through the country

Parenteral Medication Prescriptions, Dispensing and Administration Habits in Mongolia

High levels of injection prescribing were reported in Mongolia. Understanding the factors influencing the injection prescribing is essential to reduce their inappropriate use. The study evaluated the views, experiences and attitudes of community members associated with the prescribing of injections in Mongolia. A structured questionnaire focusing on respondents’ characteristics, experiences and views about injections was developed and administered face-to-face to community members in Ulaanbaatar, Mongolia. Standard descriptive statistics were used to summarize demographic data and responses to the questionnaires. Dependant variables were compared using Kruskal-Wallis Tests for independence. Statistical analyses were performed using SPSS Version 21.0. Six hundred participants were approached and the response rate was 79% (n 474). Almost half of the respondents were aged between 31 and 50 (n 228, 48.1%) and 40.9% of respondents were male (n 194). Most respondents were from Ulaanbaatar city (n 407, 85.7%). All respondents had received injections in the past and 268 (56.5%) had received injection in the past year. The most common reason for having an injection in the past year was reported as treatment of a disease (n 163, 60.8%), or for administration of vitamins (n 70, 26.1%). Injections were prescribed by a doctor (n 353, 74.9%), dispensed by a pharmacist (n 283, 59.7%) and administered by a nurse (n 277, 54.9%). Only 16% of all respondents had the expectation of receiving injections when they visited a doctor (n 77). An important perception regarding injections was that they hastened the recovery process (n 269, 56.8%). When asked their opinion about therapeutic injections, 40% of all respondents agreed that injections were a better medicine (n 190) than oral medications, with older respondents strongly agreeing (p<0.001). Based on this total sample, approximately 1891 injections per 1000 patients were administered. The excessive injection use seems to be promoted by inappropriate prescribing, dispensing and administration of medication by doctors and others