Evidence for Directed Evolution of Larger Size Motif in Arabidopsis thaliana Genome

Transcription control of gene expression depends on a variety of interactions mediated by the core promoter region, sequence specific DNA-binding proteins, and their cognate promoter elements. The prominent group of cis acting elements in plants contains an ACGT core. The cis element with this core has been shown to be involved in abscisic acid, salicylic acid, and light response. In this study, genome-wide comparison of the frequency of occurrence of two ACGT elements without any spacers as well as those separated by spacers of different length was carried out. In the first step, the frequency of occurrence of the cis element sequences across the whole genome was determined by using BLAST tool. In another approach the spacer sequence was randomized before making the query. As expected, the sequence ACGTACGT had maximum occurrence in Arabidopsis thaliana genome. As we increased the spacer length, one nucleotide at a time, the probability of its occurrence in genome decreased. This trend continued until an unexpectedly sharp rise in frequency of (ACGT)N25(ACGT). The observation of higher probability of bigger size motif suggests its directed evolution in Arabidopsis thaliana genome

Size, composition and distribution of human resource for health in India: new estimates using National Sample Survey and Registry data

Objectives We provide new estimates on size, composition and distribution of human resource for health in India and compare with the health workers population ratio as recommended by the WHO. We also estimate size of non-health workers engaged in health sector and the size of technically qualified health professionals who are not a part of the health workforce. Design Nationally representative cross-section household survey and review of published documents by the Central Bureau of Health Intelligence. Setting National Participants Head of household/key informant in a sample of 101 724 households. Interventions Not applicable. Primary and secondary outcome measures The primary outcome was the number and density of health workers,and the secondary outcome was the percentage of health workers who are technically qualified and the percentage of individuals technically qualified and not in workforce. Results The total size of health workforce estimated from the National Sample Survey (NSS) data is 3.8 million as of January 2016, which is about 1.2 million less than the total number of health professionals registered with different councils and associations. The density of doctors and nurses and midwives per 10 000 population is 20.6 according to the NSS and 26.7 based on the registry data. Health workforce density in rural India and states in eastern India is lower than the WHO minimum threshold of 22.8 per 10 000 population. More than 80% of doctors and 70% of nurses and midwives are employed in the private sector. Approximately 25% of the currently working health professionals do not have the required qualifications as laid down by professional councils, while 20% of adequately qualified doctors are not in the current workforce. Conclusions Distribution and qualification of health professionals are serious problems in India when compared with the overall size of the health workers. Policy should focus on enhancing the quality of health workers and mainstreaming professionally qualified persons into the health workforce

Effect of fingolimod on health-related quality of life in paediatric patients with multiple sclerosis: results from the phase 3 PARADIG MS Study

Background In the PARADIG MS Study, fingolimod demonstrated superior efficacy versus interferon (IFN) β-1a and comparable overall incidence of adverse events but slightly higher rate of serious adverse events in patients with paediatric-onset multiple sclerosis (PoMS). Here, we report the health-related quality of life (HRQoL) outcomes from PARADIG MS . Methods Patients with PoMS (N=215; aged 10–<18 years) were randomised to once-daily oral fingolimod (N=107) or once-weekly intramuscular IFN β-1a (N=108). HRQoL outcomes were assessed using the 23-item Pediatric Quality of Life (PedsQL) scale that comprises Physical and Psychosocial Health Summary Scores (including Emotional, Social and School Functioning). A post hoc inferential analysis evaluated changes in self-reported or parent-reported PedsQL scores from baseline up to 2 years between treatment groups using an analysis of covariance model. Results Treatment with fingolimod showed improvements versus IFN β-1a on the PedsQL scale in both the self-reported and parent-reported Total Scale Scores (4.66 vs −1.16, p≤0.001 and 2.71 vs −1.02, p≤0.05, respectively). The proportion of patients achieving a clinically meaningful improvement in the PedsQL Total Scale Score was two times higher with fingolimod versus IFN β-1a per the self-reported scores (47.5% vs 24.2%, p=0.001), and fingolimod was favoured versus IFN β-1a per the parent-reported scores (37.8% vs 24.7%, p=non-significant). Group differences in self-reported Total Scale Scores in favour of fingolimod were most pronounced among patients who had ≥2 relapses in the year prior to study entry or who showed improving or stable Expanded Disability Status Scale scores during the study. Conclusion Fingolimod improved HRQoL compared with IFN β-1a in patients with PoMS as evidenced by the self-reported and parent-reported PedsQL scores

I4S: Capturing shopper’s in-store interactions

National Research Foundation (NRF) Singapore under IDM Futures Funding; Ministry of Education, Singapore under its Academic Research Funding Tier

Sustainable food security decision-making : an agent-based modelling approach.

Ensuring a consistent and regular availability of food is crucial for food security. Food markets, supplied through both domestic production and international trade, are governed by several risks emerging from unpredictable supply chain disruptions, volatility of commodity prices, along with other unforeseen circumstances such as natural disasters. To mitigate the challenges threatening the stability of food systems, decision-making within the food sector should be enhanced and robust to accommodate any changes that might cause food shortages. Dynamic models, that can predict the behavior of food systems in order to avoid potential future knock-on effects and deficits, are incumbent to ensure the sustainable performance of food systems. This study proposes a dynamic decision-making scheme that simulates strategies of the perishable food market under different circumstances. An agent-based model (ABM) is developed and implemented using python MESA library for a case study in Qatar, illustrating the potential performance of tomato under three different scenarios to be considered, namely: (a) baseline scenario - aiming to reflect current production and market conditions; (b) water resource efficiency scenario - basing decisions on crop water requirement (CWR) depending on weather conditions; and (c) economic risk scenario - applying the concept of forward contracts to hedge against future uncertainties in crop prices. The findings of this study demonstrate that under the baseline conditions, a tomato crop can be supplied through a combination of domestic production and imports depending on the available inventories and prices imposed by exporters. The results obtained for the CWR scenario suggest the need for total reliance on imports in order to meet domestic demand, as there is potentially high-water loss, which amounts to an average of 4.9 Billion m3 per year, if tomato is grown locally. In contrast, the results from the forward contract scenario recommend a 57% dependency on local production in order to mitigate the effects of volatility in global food prices, which contributes to a 63% reduction in environmental emissions. Findings of this research provide insight into the factors that influence strategic decision making by the food sector to enhance its economic and environmental performances under diverse circumstances

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely