A Geographically-Restricted but Prevalent Mycobacterium tuberculosis Strain Identified in the West Midlands Region of the UK between 1995 and 2008

Background: We describe the identification of, and risk factors for, the single most prevalent Mycobacterium tuberculosis strain in the West Midlands region of the UK.Methodology/Principal Findings: Prospective 15-locus MIRU-VNTR genotyping of all M. tuberculosis isolates in the West Midlands between 2004 and 2008 was undertaken. Two retrospective epidemiological investigations were also undertaken using univariable and multivariable logistic regression analysis. The first study of all TB patients in the West Midlands between 2004 and 2008 identified a single prevalent strain in each of the study years (total 155/3,056 (5%) isolates). This prevalent MIRU-VNTR profile (32333 2432515314 434443183) remained clustered after typing with an additional 9-loci MIRU-VNTR and spoligotyping. The majority of these patients (122/155, 79%) resided in three major cities located within a 40 km radius. From the apparent geographical restriction, we have named this the "Mercian" strain. A multivariate analysis of all TB patients in the West Midlands identified that infection with a Mercian strain was significantly associated with being UK-born (OR = 9.03, 95% CI = 4.56-17.87, p 65 years old (OR = 0.25, 95% CI = 0.09-0.67, p < 0.01). A second more detailed investigation analyzed a cohort of 82 patients resident in Wolverhampton between 2003 and 2006. A significant association with being born in the UK remained after a multivariate analysis (OR = 9.68, 95% CI = 2.00-46.78, p < 0.01) and excess alcohol intake and cannabis use (OR = 6.26, 95% CI = 1.45-27.02, p = .01) were observed as social risk factors for infection.Conclusions/Significance: The continued consistent presence of the Mercian strain suggests ongoing community transmission. Whilst significant associations have been found, there may be other common risk factors yet to be identified. Future investigations should focus on targeting the relevant risk groups and elucidating the biological factors that mediate continued transmission of this strain

Cardiovascular profile of vasculitis patients at tertiary care center

Background: The vasculitides are a heterogenous group of conditions characterized by blood vessel inflammation and necrosis. Vasculitides are relatively uncommon conditions whose etiology is still poorly understood. Objective of the research was to study the cardiovascular profile of vasculitis patients at a tertiary care centre.Methods: The present hospital based observational study was conducted in the department of internal medicine, Sher-i-Kashmir Institute of Medical Sciences (SKIMS), Srinagar, Jammu and Kashmir, India. The study had two parts: retrospective and prospective. In the retrospective part, all patients of vasculitis who were admitted or evaluated in outpatient department (OPD) from March 2012 to September 2018, were enrolled for the analysis. In the prospective part, all patients of vasculitis admitted or evaluated in OPD from October 2018 to May 2020 were enrolled for study.Results: Out of total 77 patients studied, 39 (50.6%) were prospective cases and 38 (49.4%) cases were of retrospective nature. Normal echocardiographic and electrocardiography (ECG) findings were seen in majority of all three groups. Computed tomography (CT) angio shows involvement of right subclavian artery in 9 (40.9%) patients, 8 (36.4%) patients had involvement of left subclavian artery, 6 (27.3%) patients had involvement of arch of aorta, CT angio was suggestive of involvement left common carotid artery 5 patients, 2 patients each had involvement of celiac artery, bilateral iliac, ascending aorta, normal CT angio findings. Arterial Doppler was suggestive of involvement of right common carotid artery (CCA) and left CCA in 4 (30.8%) patients each, right superior cerebellar artery (SCA) involvement in 3 (23.1%) patients, left SCA involvement in 4 (30.8%) patients, left right brachiocephalic artery (RBA), right RA and B/L UA involvement was observed in 1 (7.7%) patient each.Conclusions: The association between cardiovascular disease and a vasculitis is well documented. our study discusses the association between cv disease and vasculitis

Support and Assessment for Fall Emergency Referrals (SAFER 1) trial protocol. Computerised on-scene decision support for emergency ambulance staff to assess and plan care for older people who have fallen: evaluation of costs and benefits using a pragmatic cluster randomised trial

Background: Many emergency ambulance calls are for older people who have fallen. As half of them are left at home, a community-based response may often be more appropriate than hospital attendance. The SAFER 1 trial will assess the costs and benefits of a new healthcare technology - hand-held computers with computerised clinical decision support (CCDS) software - to help paramedics decide who needs hospital attendance, and who can be safely left at home with referral to community falls services. Methods/Design: Pragmatic cluster randomised trial with a qualitative component. We shall allocate 72 paramedics ('clusters') at random between receiving the intervention and a control group delivering care as usual, of whom we expect 60 to complete the trial. Patients are eligible if they are aged 65 or older, live in the study area but not in residential care, and are attended by a study paramedic following an emergency call for a fall. Seven to 10 days after the index fall we shall offer patients the opportunity to opt out of further follow up. Continuing participants will receive questionnaires after one and 6 months, and we shall monitor their routine clinical data for 6 months. We shall interview 20 of these patients in depth. We shall conduct focus groups or semi-structured interviews with paramedics and other stakeholders. The primary outcome is the interval to the first subsequent reported fall (or death). We shall analyse this and other measures of outcome, process and cost by 'intention to treat'. We shall analyse qualitative data thematically. Discussion: Since the SAFER 1 trial received funding in August 2006, implementation has come to terms with ambulance service reorganisation and a new national electronic patient record in England. In response to these hurdles the research team has adapted the research design, including aspects of the intervention, to meet the needs of the ambulance services. In conclusion this complex emergency care trial will provide rigorous evidence on the clinical and cost effectiveness of CCDS for paramedics in the care of older people who have fallen

HbA1cmeasurement and relationship to incident stroke

Aims: To determine the proportion of people with diabetes who have Hb A1c measured, what proportion achieve an HbA1c level of &lt; 58 mmol/mol (7.5%), the frequency of testing and if there was any change in HbA1c level in the year before and the year after an incident stroke. Methods: This study used the Secure Anonymised Information Linkage (SAIL) databank, which stores hospital data for the whole of Wales and ~65% of Welsh general practice records, to identify cases of stroke in patients with diabetes between 2000 and 2010. These were matched against patients with diabetes but without stroke disease. We assessed the frequency of HbA1c testing and change in HbA1c in the first year after stroke. Estimation was made of the proportion of patients achieving an HbA1c measurement ≤ 58 mmol/mol (7.5%). Results: There were 1741 patients with diabetes and stroke. Of these, 1173 (67.4%) had their HbA1c checked before their stroke and 1137 (65.3%) after their stroke. In the control group of 16 838 patients with diabetes but no stroke, 8413 (49.9%) and 9288 (55.1%) had their HbA1c checked before and after the case-matched stroke date, respectively. In patients with diabetes and stroke, HbA1c fell from 7.7 to 7.3% after their stroke ( P&lt;0.001). Before the study, 55.0% of patients with stroke had an HbA1c ≥58 mmol/mol compared with 65.2% of control patients, these figures were 62.5% and 65.3% after the stroke. Conclusions: The frequency of diabetes testing was higher in patients who had experienced a stroke before and after their incident stroke compared with control patients but did not increase after their stroke. Glucose control improved significantly in the year after a stroke

Strengthening Food Security through Technologies

Securing food for 1.35 billion Indians and doubling the income of farmers by 2022, as stated by the government, are challenging tasks. India’s performance is below average in all three aspects of food security: availability, affordability, and quality and safety. It is an irony that the nation with largest cultivable land in the world (142 million ha) is facing food insecurity in spite of wide agro-ecoregions that enable cultivation of land even for three seasons in the large area. A large population (58%) depends on agriculture for its livelihood but the contribution of this sector to country's gross domestic product (GDP) has declined continuously since 1950 and was 15% in 2018. Although, the country has transformed itself from dependency on imports to selfsufficiency still the challenge is to remove the farm distress in the country. Current farmers’ field yields are lower by two to four folds than the achievable potential. In addition, the value realisation from the market is 30 to 35% only. This is because 59 % of the farmers in India do not get essential information from any agency. The major hurdles for achieving the goals set by the government are low investment in agricultural technologies, low adoption of key technologies by the farmers largely due to lack of knowledge/information, poor physical infrastructure, and involvement of large number of intermediaries in the value chains. Lack of awareness among farmers about good agricultural management practices is a key factor for stagnant productivity levels. The mind-set of all actors involved in agriculture needs to change so that they work collectively as a team instead of working independently in silos if the agrarian situation is to be transformed

Statistical Inference for Valued-Edge Networks: Generalized Exponential Random Graph Models

Across the sciences, the statistical analysis of networks is central to the production of knowledge on relational phenomena. Because of their ability to model the structural generation of networks, exponential random graph models are a ubiquitous means of analysis. However, they are limited by an inability to model networks with valued edges. We solve this problem by introducing a class of generalized exponential random graph models capable of modeling networks whose edges are valued, thus greatly expanding the scope of networks applied researchers can subject to statistical analysis

Antibiotic effectiveness on biofilm-producing Escherichia coli isolated from catheterized patients

Biofilm is one of the factors that facilitate the occurrence of catheter-associated urinary tract infection (CAUTI). Escherichia coli is reported as one of the most dominant bacteria that have virulence factors including biofilm formation. Uropathogenic E. coli (UPEC) shows increasing resistance to several antibiotics. Examination of the antibiotic sensitivity on the biofilm-producing E. coli and its activity on biofilm formation are important for selecting high effectiveness antibiotics which is beneficial for the management of CAUTI patients. A total of 35 E. coli isolates were recultured in the medium of LB agar and blood agar. The isolates were evaluated the sensitivity based on their MIC value to several antibiotics. In addition, the antibiofilm activity of the antibiotics based on their MBIC value was also evaluated. The data obtained were analyzed both descriptively and analytically. Almost the E. coli isolates have good sensitivity to meropenem antibiotics, amoxicillin-clavulanic acid, and Fosfomycin. However, among the evaluated antibiotics, only fosfomycin that showed antibiofilm activity. The different in terms of the resistance phenotype between the urinary isolates and the catheter isolates was observed. However, there were no significantly differences in the MIC value (pMIC=0.522) and the MBIC value (pMBIC = 0.523). In conclusion, the alternatives of antibiotic therapy for the planktonic bacteria are amoxicillin-clavulanic acid and fosfomycin, while for the biofilm bacteria is fosfomycin. A biofilm screening examination on the catheter to improve the effectiveness of therapy management for CAUTI patients is recommended

Assessment of platelet function in patients with stroke using multiple electrode platelet aggregometry: a prospective observational study

Background There is a link between high on-treatment platelet reactivity (HPR) and adverse vascular events in stroke. This study aimed to compare multiple electrode platelet aggregometry (MEA), in healthy subjects and ischaemic stroke patients, and between patients naive to antiplatelet drugs (AP) and those on regular low dose AP. We also aimed to determine prevalence of HPR at baseline and at 3–5 days after loading doses of aspirin. Methods Patients with first ever ischaemic stroke were age and sex-matched to a healthy control group. Three venous blood samples were collected: on admission before any treatment given (baseline); at 24 h and 3–5 days after standard treatment. MEA was determined using a Mutliplate® analyser and agonists tested were arachidonic acid (ASPI), adenosine diphosphate (ADP) and collagen (COL). Results Seventy patients (mean age 73 years [SD 13]; 42 men, 28 women) were age and sex-matched to 72 healthy subjects. Thirty-three patients were on antiplatelet drugs (AP) prior to stroke onset and 37 were AP-naive. MEA results for all agonists were significantly increased in AP-naive patients compared to healthy subjects: ADP 98 ± 31 vs 81 ± 24, p < 0.005; ASPI 117 ± 31 vs 98 ± 27, p < 0.005; COL 100 ± 25 vs 82 ± 20, p < 0.005. For patients on long term AP, 33% (10/30) of patients were considered aspirin-resistant. At 3–5 days following loading doses of aspirin, only 11.1% were aspirin resistant based on an ASPI cut-off value of 40 AU*min. Conclusions Many patients receiving low dose aspirin met the criteria of aspirin resistance but this was much lower at 3–5 days following loading doses of aspirin. Future studies are needed to establish the causes of HPR and potential benefits of individualizing AP treatment based on platelet function testing

Mir-21-Sox2 Axis Delineates Glioblastoma Subtypes with Prognostic Impact.

UNLABELLED: Glioblastoma (GBM) is the most aggressive human brain tumor. Although several molecular subtypes of GBM are recognized, a robust molecular prognostic marker has yet to be identified. Here, we report that the stemness regulator Sox2 is a new, clinically important target of microRNA-21 (miR-21) in GBM, with implications for prognosis. Using the MiR-21-Sox2 regulatory axis, approximately half of all GBM tumors present in the Cancer Genome Atlas (TCGA) and in-house patient databases can be mathematically classified into high miR-21/low Sox2 (Class A) or low miR-21/high Sox2 (Class B) subtypes. This classification reflects phenotypically and molecularly distinct characteristics and is not captured by existing classifications. Supporting the distinct nature of the subtypes, gene set enrichment analysis of the TCGA dataset predicted that Class A and Class B tumors were significantly involved in immune/inflammatory response and in chromosome organization and nervous system development, respectively. Patients with Class B tumors had longer overall survival than those with Class A tumors. Analysis of both databases indicated that the Class A/Class B classification is a better predictor of patient survival than currently used parameters. Further, manipulation of MiR-21-Sox2 levels in orthotopic mouse models supported the longer survival of the Class B subtype. The MiR-21-Sox2 association was also found in mouse neural stem cells and in the mouse brain at different developmental stages, suggesting a role in normal development. Therefore, this mechanism-based classification suggests the presence of two distinct populations of GBM patients with distinguishable phenotypic characteristics and clinical outcomes. SIGNIFICANCE STATEMENT: Molecular profiling-based classification of glioblastoma (GBM) into four subtypes has substantially increased our understanding of the biology of the disease and has pointed to the heterogeneous nature of GBM. However, this classification is not mechanism based and its prognostic value is limited. Here, we identify a new mechanism in GBM (the miR-21-Sox2 axis) that can classify ∼50% of patients into two subtypes with distinct molecular, radiological, and pathological characteristics. Importantly, this classification can predict patient survival better than the currently used parameters. Further, analysis of the miR-21-Sox2 relationship in mouse neural stem cells and in the mouse brain at different developmental stages indicates that miR-21 and Sox2 are predominantly expressed in mutually exclusive patterns, suggesting a role in normal neural development

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy