Sociodemographic Trends in National Ambulatory Care Visits for Hepatitis C Virus Infection

Poor and non-white patients are disproportionately infected with the hepatitis C virus (HCV). The objective of this research is to determine sociodemographic patterns of HCV-related ambulatory care visits over time. Data from the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey-Outpatient (NHAMCS-OPD) for the years 1997–2005 were analyzed in 3-year intervals. Demographic and other variables were compared for each period, and multivariable logistic regression was performed to examine whether the likelihood of a visit being HCV-related (versus non-HCV) was independently associated with (1) race and/or (2) Medicaid status over time. The total number of HCV-related ambulatory visits more than doubled from 3,583,585 during the years 1997–1999 to 8,027,166 during 2003–2005. During this time, the proportion of non-whites and Medicaid recipients presenting for HCV-related visits approximately doubled (non-whites: 16% vs. 33%, P = 0.04; Medicaid recipients: 10% vs. 25%, P = 0.07). In 2003–2005, HCV-related visits were more than twice as likely to occur among non-white patients vs. white patients (OR = 2.49; 95% CI: 1.60–3.86) and patients on Medicaid vs. non-Medicaid (3.49; 1.79–6.80). Our results show that HCV-associated ambulatory care visits are increasing, with a greater proportion of visits occurring among non-white patients and Medicaid recipients

Absence of Detectable Influenza RNA Transmitted via Aerosol during Various Human Respiratory Activities – Experiments from Singapore and Hong Kong

Two independent studies by two separate research teams (from Hong Kong and Singapore) failed to detect any influenza RNA landing on, or inhaled by, a life-like, human manikin target, after exposure to naturally influenza-infected volunteers. For the Hong Kong experiments, 9 influenza-infected volunteers were recruited to breathe, talk/count and cough, from 0.1 m and 0.5 m distance, onto a mouth-breathing manikin. Aerosolised droplets exhaled from the volunteers and entering the manikin’s mouth were collected with PTFE filters and an aerosol sampler, in separate experiments. Virus detection was performed using an in-house influenza RNA reverse-transcription polymerase chain reaction (RT-PCR) assay. No influenza RNA was detected from any of the PTFE filters or air samples. For the Singapore experiments, 6 influenza-infected volunteers were asked to breathe (nasal/mouth breathing), talk (counting in English/second language), cough (from 1 m/0.1 m away) and laugh, onto a thermal, breathing manikin. The manikin’s face was swabbed at specific points (around both eyes, the nostrils and the mouth) before and after exposure to each of these respiratory activities, and was cleaned between each activity with medical grade alcohol swabs. Shadowgraph imaging was used to record the generation of these respiratory aerosols from the infected volunteers and their impact onto the target manikin. No influenza RNA was detected from any of these swabs with either team’s in-house diagnostic influenza assays. All the influenza-infected volunteers had diagnostic swabs taken at recruitment that confirmed influenza (A/H1, A/H3 or B) infection with high viral loads, ranging from 105-108 copies/mL (Hong Kong volunteers/assay) and 104–107 copies/mL influenza viral RNA (Singapore volunteers/assay). These findings suggest that influenza RNA may not be readily transmitted from naturally-infected human source to susceptible recipients via these natural respiratory activities, within these exposure time-frames. Various reasons are discussed in an attempt to explain these findings.published_or_final_versio

Malignant potential of intrahepatic biliary papillomatosis: a case report and review of the literature

BACKGROUND: Biliary papillomatosis (BP) is a rare disease entity with a strong malignant potential. It is characterized by multiple papillary adenomas involving both the intrahepatic and extrahepatic biliary tree. BP was considered in the past to be a disease with low malignant potential. However, a current review of the English literature revealed a high rate of malignant occurrence of approximately 41% and histological analysis along with the expression pattern of mucin core proteins (MUC) and mucin carbohydrate antigens suggests that BP is a borderline or low grade malignant neoplasm with a high malignant potential. CASE PRESENTATION: A 68 year-old male patient was referred to our hospital due to the presence of sudden right upper quadrant abdominal pain, nausea and dark urine. Imaging workup demonstrated dilatation of the left hepatic duct without the presence of a space-occupying lesion. A left hepatectomy and cholecystectomy were carried out and histological analysis revealed a moderately to poorly differentiated carcinoma of the left hepatic duct in the background of biliary papillomatosis. Postoperative course was uneventful. Unfortunately, two years after initial diagnosis the patient rapidly deteriorated and died from multiple pulmonary secondary deposits. CONCLUSION: BP should not be considered to be a benign disease. The clinical behavior, the high recurrence rate and the even higher malignant transformation occurrence, as well as the presence of carcinogenetic indicators (K-ras mutation, overexpression of p53, MUC and Tn antigens) strongly support that BP is a low-grade neoplasm with high malignant potential

Extra-corporeal membrane oxygenation for refractory cardiogenic shock after adult cardiac surgery:a systematic review and meta-analysis

Background - Postcardiotomy cardiogenic shock (PCCS) refractory to inotropic support and intra-aortic balloon pump (IABP) occurs rarely but is almost universally fatal without mechanical circulatory support. In this systematic review and meta-analysis we looked at the evidence behind the use of veno-arterial extra-corporeal membrane oxygenation (VA ECMO) in refractory PCCS from a patient survival rate and determinants of outcome viewpoint. Methods - A systematic review was performed in January 2017 using PubMed (with no defined time period) using the keywords “postcardiotomy”, “cardiogenic shock”, “extracorporeal membrane oxygenation” and “cardiac surgery”. We excluded papers pertaining to ECMO following paediatric cardiac surgery, medical causes of cardiogenic shock, as well as case reports, review articles, expert opinions, and letters to the editor. Once the studies were collated, a meta-analysis was performed on the proportion of survivors in those papers that met the inclusion criteria. Meta-regression was performed for the most commonly reported adverse prognostic indicators (API). Results - We identified 24 studies and a cumulative pool of 1926 patients from 1992 to 2016. We tabulated the demographic data, including the strengths and weaknesses for each of the studies, outcomes of VA ECMO for refractory PCCS, complications, and APIs. All the studies were retrospective cohort studies. Meta-analysis of the moderately heterogeneous data (95% CI 0.29 to 0.34, p 70 years, 95% CI −0.057 to 0.001, P = 0.058), and long ECMO support (95% CI −0.068 to 0.166, P = 0.412). Postoperative renal failure, high EuroSCORE (>20%), diabetes mellitus, obesity, rising lactate whilst on ECMO, gastrointestinal complications had also been reported. Conclusion - Haemodynamic support with VA ECMO provides a survival benefit with reasonable intermediate and long-term outcomes. Many studies had reported advanced age, renal failure and prolonged VA ECMO support as the most likely APIs for VA ECMO in PCCS. EuroSCORE can be utilized to anticipate the need for prophylactic perioperative VA ECMO in the high-risk category. APIs can be used to aid decision-making regarding both the institution and weaning of ECMO for refractory PCCS

Spin polarization versus lifetime effects at point contacts between superconducting niobium and normal metals

Point-contact Andreev reflection spectroscopy is used to measure the spin polarization of metals but analysis of the spectra has encountered a number of serious challenges, one of which is the difficulty to distinguish the effects of spin polarization from those of the finite lifetime of Cooper pairs. We have recently confirmed the polarization-lifetime ambiguity for Nb-Co and Nb-Cu contacts and suggested to use Fermi surface mismatch, the normal reflection due to the difference of Fermi wave vectors of the two electrodes, to solve this dilemma. Here we present further experiments on contacts between superconducting Nb and the ferromagnets Fe and Ni as well as the noble metals Ag and Pt that support our previous results. Our data indicate that the Nb - normal metal interfaces have a transparency of up to about 80 per cent and a small, if not negligible, spin polarization.Comment: 7 pages, 2 figures, submitted to Proceedings of the 26th Conference on Low Temperature Physic

Impacts of climate change on plant diseases – opinions and trends

There has been a remarkable scientific output on the topic of how climate change is likely to affect plant diseases in the coming decades. This review addresses the need for review of this burgeoning literature by summarizing opinions of previous reviews and trends in recent studies on the impacts of climate change on plant health. Sudden Oak Death is used as an introductory case study: Californian forests could become even more susceptible to this emerging plant disease, if spring precipitations will be accompanied by warmer temperatures, although climate shifts may also affect the current synchronicity between host cambium activity and pathogen colonization rate. A summary of observed and predicted climate changes, as well as of direct effects of climate change on pathosystems, is provided. Prediction and management of climate change effects on plant health are complicated by indirect effects and the interactions with global change drivers. Uncertainty in models of plant disease development under climate change calls for a diversity of management strategies, from more participatory approaches to interdisciplinary science. Involvement of stakeholders and scientists from outside plant pathology shows the importance of trade-offs, for example in the land-sharing vs. sparing debate. Further research is needed on climate change and plant health in mountain, boreal, Mediterranean and tropical regions, with multiple climate change factors and scenarios (including our responses to it, e.g. the assisted migration of plants), in relation to endophytes, viruses and mycorrhiza, using long-term and large-scale datasets and considering various plant disease control methods

Nucleosome-coupled expression differences in closely-related species

<p>Abstract</p> <p>Background</p> <p>Genome-wide nucleosome occupancy is negatively related to the average level of transcription factor motif binding based on studies in yeast and several other model organisms. The degree to which nucleosome-motif interactions relate to phenotypic changes across species is, however, unknown.</p> <p>Results</p> <p>We address this challenge by generating nucleosome positioning and cell cycle expression data for <it>Saccharomyces bayanus </it>and show that differences in nucleosome occupancy reflect cell cycle expression divergence between two yeast species, <it>S. bayanus </it>and <it>S. cerevisiae</it>. Specifically, genes with nucleosome-depleted MBP1 motifs upstream of their coding sequence show periodic expression during the cell cycle, whereas genes with nucleosome-shielded motifs do not. In addition, conserved cell cycle regulatory motifs across these two species are more nucleosome-depleted compared to those that are not conserved, suggesting that the degree of conservation of regulatory sites varies, and is reflected by nucleosome occupancy patterns. Finally, many changes in cell cycle gene expression patterns across species can be correlated to changes in nucleosome occupancy on motifs (rather than to the presence or absence of motifs).</p> <p>Conclusions</p> <p>Our observations suggest that alteration of nucleosome occupancy is a previously uncharacterized feature related to the divergence of cell cycle expression between species.</p

Combining Feature Selection and Integration—A Neural Model for MT Motion Selectivity

Background: The computation of pattern motion in visual area MT based on motion input from area V1 has been investigated in many experiments and models attempting to replicate the main mechanisms. Two different core conceptual approaches were developed to explain the findings. In integrationist models the key mechanism to achieve pattern selectivity is the nonlinear integration of V1 motion activity. In contrast, selectionist models focus on the motion computation at positions with 2D features. Methodology/Principal Findings: Recent experiments revealed that neither of the two concepts alone is sufficient to explain all experimental data and that most of the existing models cannot account for the complex behaviour found. MT pattern selectivity changes over time for stimuli like type II plaids from vector average to the direction computed with an intersection of constraint rule or by feature tracking. Also, the spatial arrangement of the stimulus within the receptive field of a MT cell plays a crucial role. We propose a recurrent neural model showing how feature integration and selection can be combined into one common architecture to explain these findings. The key features of the model are the computation of 1D and 2D motion in model area V1 subpopulations that are integrated in model MT cells using feedforward and feedback processing. Our results are also in line with findings concerning the solution of the aperture problem. Conclusions/Significance: We propose a new neural model for MT pattern computation and motion disambiguation that i

Therapeutic efficacy in a hemophilia B model using a biosynthetic mRNA liver depot system

DNA-based gene therapy has considerable therapeutic potential, but the challenges associated with delivery continue to limit progress. Messenger RNA (mRNA) has the potential to provide for transient production of therapeutic proteins, without the need for nuclear delivery and without the risk of insertional mutagenesis. Here we describe the sustained delivery of therapeutic proteins in vivo in both rodents and non-human primates via nanoparticle-formulated mRNA. Nanoparticles formulated with lipids and lipid-like materials were developed for delivery of two separate mRNA transcripts encoding either human erythropoietin (hEPO) or factor IX (hFIX) protein. Dose-dependent protein production was observed for each mRNA construct. Upon delivery of hEPO mRNA in mice, serum EPO protein levels reached several orders of magnitude (>125 000-fold) over normal physiological values. Further, an increase in hematocrit (Hct) was established, demonstrating that the exogenous mRNA-derived protein maintained normal activity. The capacity of producing EPO in non-human primates via delivery of formulated mRNA was also demonstrated as elevated EPO protein levels were observed over a 72-h time course. Exemplifying the possible broad utility of mRNA drugs, therapeutically relevant amounts of human FIX (hFIX) protein were achieved upon a single intravenous dose of hFIX mRNA-loaded lipid nanoparticles in mice. In addition, therapeutic value was established within a hemophilia B (FIX knockout (KO)) mouse model by demonstrating a marked reduction in Hct loss following injury (incision) to FIX KO mice