Asymptomatic Clostridium difficile Colonisation and Onward Transmission

Introduction Combined genotyping/whole genome sequencing and epidemiological data suggest that in endemic settings only a minority of Clostridium difficile infection, CDI, is acquired from other cases. Asymptomatic patients are a potential source for many unexplained cases. Methods We prospectively screened a cohort of medical inpatients in a UK teaching hospital for asymptomatic C. difficile carriage using stool culture. Electronic and questionnaire data were used to determine risk factors for asymptomatic carriage by logistic regression. Carriage isolates were compared with all hospital/community CDI cases from the same geographic region, from 12 months before the study to 3 months after, using whole genome sequencing and hospital admission data, assessing particularly for evidence of onward transmission from asymptomatic cases. Results Of 227 participants recruited, 132 provided ≥1 stool samples for testing. 18 participants were culture-positive for C. difficile, 14/132(11%) on their first sample. Independent risk factors for asymptomatic carriage were patient reported loose/frequent stool (but not meeting CDI criteria of ≥3 unformed stools in 24 hours), previous overnight hospital stay within 6 months, and steroid/immunosuppressant medication in the last 6 months (all p≤0.02). Surprisingly antibiotic exposure in the last 6 months was independently associated with decreased risk of carriage (p = 0.005). The same risk factors were identified excluding participants reporting frequent/loose stool. 13/18(72%) asymptomatically colonised patients carried toxigenic strains from common disease-causing lineages found in cases. Several plausible transmission events to asymptomatic carriers were identified, but in this relatively small study no clear evidence of onward transmission from an asymptomatic case was seen. Conclusions Transmission events from any one asymptomatic carrier are likely to be relatively rare, but as asymptomatic carriage is common, it may still be an important source of CDI, which could be quantified in larger studies. Risk factors established for asymptomatic carriage may help identify patients for inclusion in such studies

Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus

BACKGROUND: Diabetic nephropathy is a serious complication of diabetes mellitus and is associated with considerable morbidity and high mortality. There is increasing evidence to suggest that dysregulation of the epigenome is involved in diabetic nephropathy. We assessed whether epigenetic modification of DNA methylation is associated with diabetic nephropathy in a case-control study of 192 Irish patients with type 1 diabetes mellitus (T1D). Cases had T1D and nephropathy whereas controls had T1D but no evidence of renal disease. METHODS: We performed DNA methylation profiling in bisulphite converted DNA from cases and controls using the recently developed Illumina Infinium(R) HumanMethylation27 BeadChip, that enables the direct investigation of 27,578 individual cytosines at CpG loci throughout the genome, which are focused on the promoter regions of 14,495 genes. RESULTS: Singular Value Decomposition (SVD) analysis indicated that significant components of DNA methylation variation correlated with patient age, time to onset of diabetic nephropathy, and sex. Adjusting for confounding factors using multivariate Cox-regression analyses, and with a false discovery rate (FDR) of 0.05, we observed 19 CpG sites that demonstrated correlations with time to development of diabetic nephropathy. Of note, this included one CpG site located 18 bp upstream of the transcription start site of UNC13B, a gene in which the first intronic SNP rs13293564 has recently been reported to be associated with diabetic nephropathy. CONCLUSION: This high throughput platform was able to successfully interrogate the methylation state of individual cytosines and identified 19 prospective CpG sites associated with risk of diabetic nephropathy. These differences in DNA methylation are worthy of further follow-up in replication studies using larger cohorts of diabetic patients with and without nephropathy

Multiplexed, High Density Electrophysiology with Nanofabricated Neural Probes

Extracellular electrode arrays can reveal the neuronal network correlates of behavior with single-cell, single-spike, and sub-millisecond resolution. However, implantable electrodes are inherently invasive, and efforts to scale up the number and density of recording sites must compromise on device size in order to connect the electrodes. Here, we report on silicon-based neural probes employing nanofabricated, high-density electrical leads. Furthermore, we address the challenge of reading out multichannel data with an application-specific integrated circuit (ASIC) performing signal amplification, band-pass filtering, and multiplexing functions. We demonstrate high spatial resolution extracellular measurements with a fully integrated, low noise 64-channel system weighing just 330 mg. The on-chip multiplexers make possible recordings with substantially fewer external wires than the number of input channels. By combining nanofabricated probes with ASICs we have implemented a system for performing large-scale, high-density electrophysiology in small, freely behaving animals that is both minimally invasive and highly scalable

Grand challenges in biodiversity-ecosystem functioning research in the era of science-policy platforms require explicit consideration of feedbacks

Feedbacks are an essential feature of resilient socio-economic systems, yet the feedbacks between biodiversity, ecosystem services and human wellbeing are not fully accounted for in global policy efforts that consider future scenarios for human activities and their consequences for nature. Failure to integrate feedbacks in our knowledge frameworks exacerbates uncertainty in future projections and potentially prevents us from realizing the full benefits of actions we can take to enhance sustainability. We identify six scientific research challenges that, if addressed, could allow future policy, conservation and monitoring efforts to quantitatively account for ecosystem and societal consequences of biodiversity change. Placing feedbacks prominently in our frameworks would lead to (i) coordinated observation of biodiversity change, ecosystem functions and human actions, (ii) joint experiment and observation programmes, (iii) more effective use of emerging technologies in biodiversity science and policy, and (iv) a more inclusive and integrated global community of biodiversity observers. To meet these challenges, we outline a five-point action plan for collaboration and connection among scientists and policymakers that emphasizes diversity, inclusion and open access. Efforts to protect biodiversity require the best possible scientific understanding of human activities, biodiversity trends, ecosystem functions and—critically—the feedbacks among them

Strategies to reduce clinical inertia in hypertensive kidney transplant recipients

<p>Abstract</p> <p>Background</p> <p>Many kidney transplant recipients have hypertension. Elevated systolic blood pressures are associated with lower patient and kidney allograft survival.</p> <p>Methods</p> <p>This retrospective analysis examined the prevalence of clinical inertia (failure to initiate or increase therapy) in the treatment of hypertension before and after the introduction of an automated device (BpTRU) in the kidney transplant clinic.</p> <p>Results</p> <p>Historically only 36% (49/134) of patients were prescribed a change in therapy despite a systolic blood pressure ≥ 130 mmHg. After the introduction of BpTRU, 56% (62/110) of the patients had a change in therapy. In a multivariate logistic regression analysis of the entire cohort (n = 244) therapeutic changes were associated with higher blood pressures (OR 1.08 per mmHg, 95% CI 1.04–1.12) and use of the BpTRU (OR 2.12, 95% CI 1.72–3.83). In addition patients on more medications were also more likely to have a change in therapy.</p> <p>Conclusion</p> <p>Blood pressure measurement with automated devices may help reduce clinical inertia in the kidney transplant clinic.</p

Declining Burden of Malaria Over two Decades in a Rural Community of Muheza District, North-Eastern Tanzania.

The recently reported declining burden of malaria in some African countries has been attributed to scaling-up of different interventions although in some areas, these changes started before implementation of major interventions. This study assessed the long-term trends of malaria burden for 20 years (1992--2012) in Magoda and for 15 years in Mpapayu village of Muheza district, north-eastern Tanzania, in relation to different interventions as well as changing national malaria control policies.\ud Repeated cross-sectional surveys recruited individuals aged 0 -- 19 years from the two villages whereby blood smears were collected for detection of malaria parasites by microscopy. Prevalence of Plasmodium falciparum infections and other indices of malaria burden (prevalence of anaemia, splenomegaly and gametocytes) were compared across the years and between the study villages. Major interventions deployed including mobile clinic, bed nets and other research activities, and changes in national malaria control policies were also marked. In Magoda, the prevalence of P. falciparum infections initially decreased between 1992 and 1996 (from 83.5 to 62.0%), stabilized between 1996 and 1997, and further declined to 34.4% in 2004. A temporary increase between 2004 and 2008 was followed by a progressive decline to 7.2% in 2012, which is more than 10-fold decrease since 1992. In Mpapayu (from 1998), the highest prevalence was 81.5% in 1999 and it decreased to 25% in 2004. After a slight increase in 2008, a steady decline followed, reaching <5% from 2011 onwards. Bed net usage was high in both villages from 1999 to 2004 (>=88%) but it decreased between 2008 and 2012 (range, 28% - 68%). After adjusting for the effects of bed nets, age, fever and year of study, the risk of P. falciparum infections decreased significantly by >=97% in both villages between 1999 and 2012 (p < 0.001). The prevalence of splenomegaly (>40% to <1%) and gametocytes (23% to <1%) also decreased in both villages.Discussion and conclusionsA remarkable decline in the burden of malaria occurred between 1992 and 2012 and the initial decline (1992 -- 2004) was most likely due to deployment of interventions, such as bed nets, and better services through research activities. Apart from changes of drug policies, the steady decline observed from 2008 occurred when bed net coverage was low suggesting that other factors contributed to the most recent pattern. These results suggest that continued monitoring is required to determine causes of the changing malaria epidemiology and also to monitor the progress towards maintaining low malaria transmission and reaching related millennium development goals

Dinosaur Speed Demon: The Caudal Musculature of Carnotaurus sastrei and Implications for the Evolution of South American Abelisaurids

In the South American abelisaurids Carnotaurus sastrei, Aucasaurus garridoi, and, to a lesser extent Skorpiovenator bustingorryi, the anterior caudal ribs project at a high dorsolateral inclination and have interlocking lateral tips. This unique morphology facilitated the expansion of the caudal hypaxial musculature at the expense of the epaxial musculature. Distinct ridges on the ventrolateral surfaces of the caudal ribs of Aucasaurus garridoi are interpreted as attachment scars from the intra caudofemoralis/ilio-ischiocaudalis septa, and confirm that the M. caudofemoralis of advanced South American abelisaurids originated from a portion of the caudal ribs. Digital muscle models indicate that, relative to its overall body size, Carnotaurus sastrei had a substantially larger M. caudofemoralis than any other theropod yet studied. In most non-avian theropods, as in many extant sauropsids, the M. caudofemoralis served as the primary femoral retractor muscle during the locomotive power stroke. This large investment in the M. caudofemoralis suggests that Carnotaurus sastrei had the potential for great cursorial abilities, particularly short-burst sprinting. However, the tightly interlocking morphology of the anterior caudal vertebrae implies a reduced ability to make tight turns. Examination of these vertebral traits in evolutionary context reveals a progressive sequence of increasing caudofemoral mass and tail rigidity among the Abelisauridae of South America

Evidence for Avian Intrathoracic Air Sacs in a New Predatory Dinosaur from Argentina

Background: Living birds possess a unique heterogeneous pulmonary system composed of a rigid, dorsally-anchored lung and several compliant air sacs that operate as bellows, driving inspired air through the lung. Evidence from the fossil record for the origin and evolution of this system is extremely limited, because lungs do not fossilize and because the bellow-like air sacs in living birds only rarely penetrate (pneumatize) skeletal bone and thus leave a record of their presence. Methodology/Principal Findings: We describe a new predatory dinosaur from Upper Cretaceous rocks in Argentina, Aerosteon riocoloradensis gen. et sp. nov., that exhibits extreme pneumatization of skeletal bone, including pneumatic hollowing of the furcula and ilium. In living birds, these two bones are pneumatized by diverticulae of air sacs (clavicular, abdominal) that are involved in pulmonary ventilation. We also describe several pneumatized gastralia (‘‘stomach ribs’’), which suggest that diverticulae of the air sac system were present in surface tissues of the thorax. Conclusions/Significance: We present a four-phase model for the evolution of avian air sacs and costosternal-driven lung ventilation based on the known fossil record of theropod dinosaurs and osteological correlates in extant birds: (1) Phase I—Elaboration of paraxial cervical air sacs in basal theropods no later than the earliest Late Triassic. (2) Phase II—Differentiation of avian ventilatory air sacs, including both cranial (clavicular air sac) and caudal (abdominal air sac) divisions, in basal tetanurans during the Jurassic. A heterogeneous respiratory tract wit