Miracle-dz/UniFAR-FTUs huggingface dataset:
QMRA for Drinking Water: 2. The Effect of Pathogen Clustering in Single‐Hit Dose‐Response Models

Spatial and/or temporal clustering of pathogens will invalidate the commonly used assumption of Poisson‐distributed pathogen counts (doses) in quantitative microbial risk assessment. In this work, the theoretically predicted effect of spatial clustering in conventional “single‐hit” dose‐response models is investigated by employing the stuttering Poisson distribution, a very general family of count distributions that naturally models pathogen clustering and contains the Poisson and negative binomial distributions as special cases. The analysis is facilitated by formulating the dose‐response models in terms of probability generating functions. It is shown formally that the theoretical single‐hit risk obtained with a stuttering Poisson distribution is lower than that obtained with a Poisson distribution, assuming identical mean doses. A similar result holds for mixed Poisson distributions. Numerical examples indicate that the theoretical single‐hit risk is fairly insensitive to moderate clustering, though the effect tends to be more pronounced for low mean doses. Furthermore, using Jensen's inequality, an upper bound on risk is derived that tends to better approximate the exact theoretical single‐hit risk for highly overdispersed dose distributions. The bound holds with any dose distribution (characterized by its mean and zero inflation index) and any conditional dose‐response model that is concave in the dose variable. Its application is exemplified with published data from Norovirus feeding trials, for which some of the administered doses were prepared from an inoculum of aggregated viruses. The potential implications of clustering for dose‐response assessment as well as practical risk characterization are discussed.
Virtual reality and innovation networks: opportunity exploitation in dynamic SMEs

This paper examines the process of technological and organisational innovation within a SME (small and medium-sized enterprise) located in a relatively remote area of northwest England. Supply chain networks provide a mechanism by which closer relations can create opportunities to improve competitiveness of all the partners. It is argued that these opportunities can be extended geographically by the use of information and communications technologies (ICTs). The paper focuses on the accumulation of innovation capabilities developed through RWL's close relationship with its main customer, BNFL, and other firms within the supply chain. These relationships have enabled knowledge to be transferred both upstream and downstream creating a "virtual cluster" facilitated through reciprocal relationships between the main actors. Our conclusion is that virtual technologies depend heavily on shared perceptions of those participating in such networks. Furthermore, close relationships central to the sharing of tacit knowledge are best achieved through regular face-to-face interaction.
Chronic inflammatory demyelinating polyneuropathy associated with membranous glomerulonephritis: case report

A case of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) with Membranous Glomerulonephritis (MGN) is reported. This is the second case recorded in the literature and the article compares this case with the other reported case, including immunological implications.
On an Isoperimetric Problem with a Competing Nonlocal Term I: The Planar Case

This paper is concerned with a study of the classical isoperimetric problem modified by an addition of a nonlocal repulsive term. We characterize existence, nonexistence, and radial symmetry of the minimizers as a function of mass in the situation where the nonlocal term is generated by a kernel given by an inverse power of the distance. We prove that minimizers of this problem exist for sufficiently small masses and are given by disks with prescribed mass below a certain threshold when the interfacial term in the energy is dominant. At the same time, we prove that minimizers fail to exist for sufficiently large masses due to the tendency of the low‐energy configuration to split into smaller pieces when the nonlocal term in the energy is dominant. In the latter regime, we also establish linear scaling of energy with mass, suggesting that for large masses low‐energy configurations consist of many roughly equal‐size pieces far apart. In the case of slowly decaying kernels, we give a complete characterization of the minimizers. © 2012 Wiley Periodicals, Inc.
Avalanche Photodiodes Based on the AlInAsSb Materials System

We report avalanche photodiodes (APDs) fabricated from high-aluminum-content Al<italic><sub>x</sub></italic>In<sub> 1−</sub><italic><sub>x</sub></italic>As<italic><sub>y</sub></italic>Sb<sub>1−</sub><italic><sub>y</sub> </italic> lattice matched to GaSb that is grown within the miscibility gap using a digital alloy approach. The material was initially characterized through a series of Al<italic><sub>x</sub></italic>In<sub>1−</sub><italic><sub>x </sub></italic>As<italic><sub>y</sub></italic>Sb<sub>1−</sub><italic><sub>y</sub></italic> (<italic>x</italic> = 0.3, 0.4, 0.5, 0.6, 0.7) p-i-n structures. In order to achieve operation at telecommunications wavelengths, an Al<italic><sub>x</sub></italic>In<sub>1−</sub><italic><sub>x</sub></italic>As<italic><sub>y</sub></italic>Sb <sub>1−</sub><italic><sub>y</sub></italic> separate absorption, charge, and multiplication APD has been developed. Very low excess noise, as characterized by <italic>k</italic> ∼0.01−0.05, has been achieved.
Estimating group size from human speech: Three's a conversation, but four's a crowd

Much previous research has examined various aspects of auditory processing, including the localization of sounds, and the influence of lexical and indexical information on language processing. In the present set of experiments we explored the ability of listeners to estimate the number of speakers in a group solely from the information in an auditory signal. The bound on accurately estimating the number of simultaneous speakers is 3. We suggest that subitization—the ability to estimate numerosity of visual and auditory elements without explicitly counting these elements—rather than the capacity of short-term memory, may underlie this limitation. The cognitive constraint on estimating the number of simultaneous speakers may have implications for a wide variety of seemingly unrelated psychological phenomena.
Meta-analysis: Potentials and promise

The number of papers published on meta-analyses in medical research has increased sharply in the past 10 years (fig 1). The merits and perils of the somewhat mysterious procedure of meta-analysis, however, continue to be debated in the medical community.1 23 What, then, is meta-analysis? A useful definition was given by Huque: “A statistical analysis that combines or integrates the results of several independent clinical trials considered by the analyst to be ‘combinable. ’” 4 The terminology, however, is still debated, and expressions used concurrently include “overview,” “pooling,” and “quantitative synthesis. ” We believe that the term meta-analysis should be used to describe the statistical integration of separate studies, whereas “systematic review” is most appropriate for denoting any review of a body of data that uses clearly defined methods and criteria (box). Systematic reviews can include meta-analyses, appraisals of single trials, and other sources of evidence.6 In this article we examine the potentials and promise of meta-analysis of randomised controlled trials. In later articles of this series we will consider the practical steps involved in meta-analysis,7 examine various extensions beyond the calculation of a combined estimate,8 address potential biases and discuss strategies to detect and minimise the influence of these in meta-analysis of randomised trials9 and of observational studies.10 We will conclude with a discussion of unresolved issues and future developments.11 Details of relevant software will appear on the BMJ's website at the end of the series. Fig 1 Number of publications about meta-analysis, 1987–96 (results from Medline search using text word and medical subject heading “meta-analysis”) #### What's in a name? The case for “meta-analysis” The term meta-analysis for statistically combining and analysing data from separate studies is appropriate because:
What Would Pediatric Infectious Disease Consultants Recommend for Management of Culture-Negative Acute Hematogenous Osteomyelitis?

Objective: To assess the opinion of pediatric infectious disease (PID) specialists regarding the management of culture-negative acute hematogenous osteomyelitis. Methods: A questionnaire that included a hypothetical case scenario of a 4-year-old boy with culture-negative osteomyelitis was distributed via a Web-based system to PID specialists across the United States. Results: Of 481 eligible participants surveyed, 147 (31%) responded. For initial therapy of osteomyelitis, 37% of respondents chose a &bgr;-lactam, 24% chose clindamycin, 10% chose vancomycin as the sole therapy, and 29% chose a combination of these. The initial choice of antibiotics was correlated with the reported incidence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) in the institution (P < 0.01). In areas where the prevalence of CA-MRSA was intermediate (between 25% and 50%), the choice of antibiotics was more heterogeneous. For change from intravenous to oral therapy, approximately 70% of respondents would change to oral therapy sooner than 3 weeks depending on clinical, laboratory, and social factors. After significant clinical and laboratory (sedimentation rate and C-reactive protein) improvements, most respondents (69%) chose to treat for a total duration (intravenous and oral) of 3 to 4 weeks. Conclusions: This study illustrates that the empiric choice of antibiotics for treatment of acute hematogenous osteomyelitis was driven by the local prevalence of CA-MRSA. When the prevalence of CA-MRSA was intermediate, the recommendations for management of bone infections were more heterogeneous. Clinical trials are needed to compare the effect of different management strategies on outcome, side effects, and costs. Level of Evidence: Level V.
Identification of specific EP receptors responsible for the hemodynamic effects of PGE 2

LAURENT P. AUDOLY,1 STEPHEN L. TILLEY,2 JENNIFER GOULET,2 MIKELLE KEY,2 MYTRANG NGUYEN,2 JEFFREY L. STOCK,3 JOHN D. MCNEISH,3 BEVERLY H. KOLLER,2 AND THOMAS M. COFFMAN1 1Department of Medicine, Duke University and Durham Veterans Affairs Medical Centers, Durham 27710; 2Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599; and 3Center for Experimental Therapeutics, Pfizer, Groton, Connecticut 06340
Palm vitamin E and the healing of ethanol-induced gastric lesions.

The main focus of the study was to examine the effect of palm vitamin E (a tocotrienol-enriched fraction of palm oil) on the healing of ethanol-induced gastric mucosal lesions. The study was divided into three sections.Study 1 determined the gastric content of vitamin E after dietary supplementation with palm vitamin E for 3 weeks. Seven rats were fed a normal diet and another 7 were fed a palm vitamin E-enriched diet (150 mg/kg food). The gastric content of vitamin E levels were higher in rats fed with a palm vitamin E-enriched diet (p<0.01). Study 2 determined the time-dependent effects of palm vitamin E on gastric lesions and gastric acidity postethanol administration. Two groups of rats were fed either a normal rat diet or a palm vitamin E-enriched diet (150 mg/kg food). After 3 weeks, the control and a treated group received a single intragastric dose of 100% ethanol. Assessment of gastric lesions after 1 week showed a lower gastric lesion index in the palm vitamin E group compared with the controls (p<0.05) but there was no difference in the gastric acid content after 1 week between the two groups. Study 3 determined the effects of palm vitamin E on the gastric tissue content of malondialdehyde (MDA), PGE2 and gastric acidity without ethanol administration. The MDA content was lower in the palm vitamin E-treated group (p<0.05). However, the gastric acid and PGE2 content in both groups did not differ. The findings suggest that feeding with a palm vitamin E-enriched diet (150 mg/kg food) for 3 weeks resulted in a significant concentration of vitamin E in the gastric tissue. It was concluded that palm vitamin E may promote the healing of ethanol-induced gastric lesions through minimizing the lipid preoccupation process in the gastric mucous.
Developing Effective Interfaces for Cultural Heritage 3D Immersive Environments

Although the advantages of the use of 3D Immersive Virtual Environments for the presentation and communica- tion of Cultural Heritage have been demonstrated, the user interfaces and interaction techniques (in software and hardware) that are best suited have not yet been completely identified and deployed. This paper describes research conducted for developing and studying the usability of a historical town 3D Virtual Tour. For this, usability meth- ods combined with head-eyetracking technology were used to explore the suitability of these interfaces. The paper also reflects on issues raised during the design of the testing system for this experience. It is expected the results of this research will contribute towards developing effective interfaces for 3D immersive technologies as well as building a repository of lessons learned from evaluation.
Temporal lobe involvement in Japanese encephalitis: problems in differential diagnosis.

BACKGROUND AND PURPOSE On MR imaging and CT, Japanese encephalitis (JE) shows lesions in the thalami, substantia nigra, basal ganglia, cerebral cortex, cerebellum, brain stem, and white matter, whereas temporal lobe involvement is characteristically seen in Herpes simplex encephalitis (HSE). Temporal lobe involvement in JE may cause problems in differentiating it from HSE. We undertook this study to show the temporal lobe involvement pattern in JE and highlight differentiating features from temporal lobe involvement in HSE. METHODS Sixty-two patients with JE underwent CT or MR imaging or both. MR imaging was done in 53 and CT in 53. The diagnosis of JE was confirmed by cerebrospinal fluid (CSF) IgM enzyme-linked immunosorbent assay. RESULTS Eleven (17.7%) patients showed temporal lobe involvement with abnormal MR imaging in all. All the patients showed hippocampal involvement. Two patients showed extension of lesions into the amygdala and uncus with insular involvement in 1. The rest of the temporal lobe was spared. All patients had thalamic and substantia nigra involvement with basal ganglia involvement in 7. Six of 9 CT scans were abnormal and the temporal lesions were seen in 2. CONCLUSIONS The temporal lobe involvement pattern is fairly characteristic and mostly involves the hippocampus, usually sparing the rest of the temporal lobe. This and the concurrent involvement of the thalami, substantia nigra (SN), and basal ganglia allow differentiation from HSE. However, if the temporal lobe involvement is more severe, laboratory tests may be the only way to differentiate it from HSE, and it may be prudent to start antiviral therapy in the interim period.
Overexpression of CsrA (BB0184) Alters the Morphology and Antigen Profiles of Borrelia burgdorferi

ABSTRACT Borrelia burgdorferi, the agent of Lyme disease, alters its gene expression in response to highly disparate environmental signals encountered in its hosts. Among the relatively few regulators of adaptive gene expression present in the borrelial genome is an open reading frame (ORF), BB0184, annotated as CsrA (carbon storage regulator A). CsrA, in several bacterial species, has been characterized as a small RNA binding protein that functions as a global regulator affecting mRNA stability or levels of translation of multiple ORFs. Consistent with known functions of CsrA, overexpression of CsrA from B. burgdorferi (CsrABb) in Escherichia coli resulted in reduced accumulation of glycogen. We determined that csrABb is part of the flgK motility operon and that the synthesis of CsrABb was increased when B. burgdorferi was propagated under fed-tick conditions. Overexpression of CsrABb in B. burgdorferi strain B31 (ML23, lp25-negative clonal isolate) resulted in a clone, designated ES25, which exhibited alterations in colony morphology and a significant reduction in the levels of FlaB. Several lipoproteins previously characterized as playing a role in infectivity were also altered in ES25. Real-time reverse transcription-PCR analysis of RNA revealed significant differences in the transcriptional levels of ospC in ES25, while there were no such differences in the levels of other transcripts, suggesting posttranscriptional regulation of expression of these latter genes. These observations indicate that CsrABb plays a role in the regulation of expression of pathophysiological determinants of B. burgdorferi, and further characterization of CsrABb will help in better understanding of the regulators of gene expression in B. burgdorferi.
Elucidating the differences in pathogenicity between hepatitis E virus genotypes: The quest continues

Hepatitis E virus (HEV) is an emerging pathogen and the most common cause of acute hepatitis. Five genotypes have been described to be capable of infecting humans (genotype 1, gt2, gt3, gt4, and gt7), and two genotypes (gt5 and gt6) have been described that only affect other animals. HEV typically causes an acute self-limiting illness, and not all infections develop overt clinical signs. After an incubation period of 2 to 6 weeks, nonspecific symptoms, such as fever, nausea, abdominal pain, vomiting, anorexia, jaundice, and malaise, can develop. Excess mortality can be seen in individuals with an underlying chronic liver disease, in immunosuppressed patients, and in pregnant women. HEV infection during pregnancy can take a fulminant course, resulting in fulminant hepatic failure, membrane rupture, spontaneous abortion, and stillbirth. Numerous studies have shown a high mortality (20%-25%) in pregnant women, especially during the third trimester, and children who survive have increased neonatal morbidity and mortality. Importantly, HEV-induced complications during pregnancy are uniquely seen in developing countries and seem to be restricted to infections of gt1 and gt2. Only two cases of gt3 infection in pregnant women have been reported in industrialized countries, one occurring at the end of the second trimester and the second during week 34 of gestation. In both cases, no hospitalization was required and mother and child had a positive outcome. The cause of excess maternal mortality in HEVinfected pregnant women is currently not known and has been the subject of many studies. In this issue, Knegendorf et al. describe a placental-derived cell culture system (JEG-3) capable of supporting HEV replication and assessed potential genotype-dependent differences. While JEG-3 cells supported subgenomic HEV replication of gt3 (strain Kernow-C1 clone p6) to a similar level as HepG2 hepatocellular carcinoma cells, gt1 (strain Sar55) replication occurred but at a much lower rate compared to that in HepG2 cells. The authors also successfully demonstrated HEV infection in JEG-3 cells after electroporation of fulllength HEV RNA of gt3, including virion assembly and release of infectious viral particles that have similar biophysical characteristics as HEV particles typically produced in HepG2 cells. Infection with full-length gt1 HEV was not successful, but it remains unclear whether this is typical for gt1 viruses in JEG-3 cells or rather due to the inherent low replicative capacity of Sar55 in cell culture; most likely it is due to the latter. Interestingly, we recently showed that Sar55 propagates more efficiently and replicates at a much higher level in immune-deficient mice with humanized liver Abbreviations: gt, genotype; HEV, hepatitis E virus; IFNa-2a, interferon alpha-2a; RBV, ribavirin.
Patho-physiological observations of Sertoli cells in patients with germinal aplasia or severe germ cell depletion. Ultrastructural findings and hormone levels.

The purpose of this study was to examine the fine structure of Sertoli cells in patients with a severe or complete depletion of germ cells. In normal seminiferous tubules Sertoli cells are characterized by a cytoplasm rich in the common cellular organelles, particularly smooth endoplasmic reticulum and mitochondria. Lipid droplets, Golgi, rough endoplasmic reticulum, dense granules, annulate Iamellae and crystals of Charcot-B#{246}ttcher are also present, although the latter two Structures are not constantly observed. Occluding junctional complexes join adjacent Sertoli cells near the base of the seminiferous epithelium. In patients exhibiting germinal aplasia or severe germ cell depletion there are three morphological features of the Sertoli cells which stand out: 1) A marked increase in the number of fine filaments in the basal portion of the Sertoli cell cytoplasm. In some of these regions few other organdIes are present; 2) Extensive junctional complexes between neighboring Sertoli cells extending from the base of the tubule to the lumen; and 3) Elaborate interdigitations between the plasma membrane of adjacent Sertoli cells. In addition to these special features, many areas of Sertoli cells in germinal aplasia show the common organdies found in normal humans. It has previously been assumed that Sertoli cells are normal in patients with germinal aplasia, but the present ultrastructural study demonstrates that they possess certain morphological abnormalities. These observations are consistent with the conjecture that in patients with severe germ cell depletion the increase in plasma FSH may be due to impaired Sertoli cell function resulting in diminished feedback inhibition of gonadotropin release.
The Rice High-Affinity Potassium Transporter1;1 Is Involved in Salt Tolerance and Regulated by an MYB-Type Transcription Factor1[OPEN]

A rice potassium transporter contributes to salt tolerance and is regulated by a transcription factor. Sodium transporters play key roles in plant tolerance to salt stress. Here, we report that a member of the High-Affinity K+ Transporter (HKT) family, OsHKT1;1, in rice (Oryza sativa ‘Nipponbare’) plays an important role in reducing Na+ accumulation in shoots to cope with salt stress. The oshkt1;1 mutant plants displayed hypersensitivity to salt stress. They contained less Na+ in the phloem sap and accumulated more Na+ in the shoots compared with the wild type. OsHKT1;1 was expressed mainly in the phloem of leaf blades and up-regulated in response to salt stress. Using a yeast one-hybrid approach, a novel MYB coiled-coil type transcription factor, OsMYBc, was found to bind to the OsHKT1;1 promoter. In vivo chromatin immunoprecipitation and in vitro electrophoresis mobility shift assays demonstrated that OsMYBc binds to AAANATNC(C/T) fragments within the OsHKT1;1 promoter. Mutation of the OsMYBc-binding nucleotides resulted in a decrease in promoter activity of OsHKT1;1. Knockout of OsMYBc resulted in a reduction in NaCl-induced expression of OsHKT1;1 and salt sensitivity. Taken together, these results suggest that OsHKT1;1 has a role in controlling Na+ concentration and preventing sodium toxicity in leaf blades and is regulated by the OsMYBc transcription factor.