Are there relevant animal models to set research priorities in LUTD? ICI-RS 2019.
To discuss animal models of lower urinary tract disorders (LUTD) and their translational impact. Report of discussions based on presented literature-search based reviews relevant for the purpose. Animal models can be used to investigate fundamental biological mechanisms, but also as tools to elucidate aspects of the pathogenesis of disease and to provide early evidence of any safety risk. Several different models may be required to obtain information that can have a translational impact. The term "translational research" covers not only the process of directly transferring knowledge from basic sciences to human trials to produce new drugs, devices, and treatment options for patients (T1 type translation) but also the implementation of early clinical research findings (phases I-III) into practice to improve care for patients (T2 type). Direct transfer of animal data to T2 is rarely possible, and the process often does not continue after the first trials in humans (phase I). It should be emphasized that many preclinical observations do not have (and do not need to have) immediate translational impact. No single animal model can mimic the complexity of the human disease. Still, animal models can be useful for gaining information on LUT function in humans, for elucidating pathophysiological mechanisms, and for the definition of targets for future drugs to treat LUT disorders.


Word-sentences and an interaction-based account of language evolution.
Considerations from an interaction-based approach to the evolution of language and the role of word-sentences therein show that the object-attribute ontology is arrived at a much later stage. Therefore, Hurford's arguments, by focusing on the predicate-argument structure, seem to miss out on most of the interesting aspects of the early stages in language evolution.


Mystacial Whisker Layout and Musculature in the Guinea Pig (Cavia porcellus): A Social, Diurnal Mammal.
All mammals (apart from apes and humans) have whiskers that make use of a similar muscle arrangement. Whisker specialists, such as rats and mice, tend to be nocturnal and arboreal, relying on their whisker sense of touch to guide exploration around tree canopies at night. As such, nocturnal arboreal rodents have many whiskers that are organised into a grid-like pattern, and moved using a complex array of muscles. Indeed, most arboreal, nocturnal mammals tend to have specialised whiskers that are longer and arranged in a dense, regular grid, compared with terrestrial, diurnal mammals. The guinea pig diverged early from murid rodents (around 75 million years ago), and are ground-dwelling, diurnal animals. It would be predicted that, as a terrestrial mammal, they may have less whiskers and a reduced muscle architecture compared to arboreal, nocturnal rodents. We examined the mystacial whisker layout, musculature and movement capacity of Guinea pig (Cavia porcellus) whiskers and found that they did indeed have a disorganized whisker layout, with a fortification around the eye area. In addition, there was a reduction in musculature, especially in the intrinsic muscles. Despite guinea pigs not cyclically moving their whiskers, the mystacial musculature was still very similar to that of murid rodents. We suggest that the conserved presence of whisker layout and musculature, even in visual mammals such as primates and guinea pigs, may indicate that whiskers still play an important role in these animals, including protecting the eyes and being involved in tactile social behaviors. Anat Rec, 300:527-536, 2017. © 2016 Wiley Periodicals, Inc.


Two sides of a coin: Perpetrators and survivors perspectives on the triad of alcohol, intimate partner violence and mental health in South India.
The present study explored the intersection among alcohol consumption, gender roles, intimate partner violence (IPV) and mental health from the perspective of heavy drinking men who also perpetrate IPV (perpetrators) and their spouses (survivors). Interpretive phenomenological approach was used, and in-depth interviews were conducted with adult married heavy drinking men who reported to have perpetrated IPV (N=10) and their spouses (N=10). These interviews were audio-recorded, and salient themes were generated using the NVivo software. Findings indicated a deeply embedded association among alcohol consumption, IPV, and mental health, with culturally sanctioned gender norms strongly contributing to this association. There was evidence for anxiety and depression in the survivors and emotional-behavioural and academic difficulties in their children. The study provides valuable insight into the intersecting problems of alcohol and IPV, which independently and together signify an emergent public health problem that can have immense ramifications on mental health of individuals and families.


Cognate MHC-TCR interaction leads to apoptosis of antigen-presenting cells.
Antigen presentation to T lymphocytes has been characterized extensively in terms of T lymphocyte activation and eventual cell death. In contrast, little is known about the consequences of antigen presentation for the antigen-presenting cell (APC). We have determined the outcome of major histocompatibility complex class II-restricted peptide presentation to a specific T cell. We demonstrate that specific T lymphocyte interaction with peptide-presenting APCs led to apoptosis in the APC population. In contrast, T lymphocyte interaction with nonpeptide-loaded APCs or APCs loaded with monosubstituted peptide failed to induce T lymphocyte secretion of interleukin-2 and APC apoptosis. Phosphatidylserine externalization and mitochondrial depolarization were used to evaluate APC apoptosis. Fas/Fas ligand interactions were not required, but cytoskeletal integrity and caspase activation were essential for APC apoptosis. Antigen presentation leading to T lymphocyte activation is therefore coordinated with apoptosis in the APC population and could provide a mechanism of immune response regulation by eliminating APCs, which have fulfilled their role as specific ligands for T lymphocyte activation. This pathway may have particular importance for APCs, which are not sensitive to death receptor-induced apoptosis.


Minimal Interference from Possessor Phrases in the Production of Subject-Verb Agreement.
We explore the language production process by eliciting subject-verb agreement errors. Participants were asked to create complete sentences from sentence beginnings such as The elf's/elves' house with the tiny window/windows and The statue in the elf's/elves' gardens. These are subject noun phrases containing a head noun and controller of agreement (statue) and two nonheads, a "local noun" (window(s)/garden(s)), and a possessor noun (elf's/elves'). Past research has shown that a plural nonhead noun (an "attractor") within a subject noun phrase triggers the production of verb agreement errors, and further, that the nearer the attractor to the head noun, the greater the interference. This effect can be interpreted in terms of relative hierarchical distance from the head noun, or via a processing window account, which claims that during production, there is a window in which the head and modifying material may be co-active, and an attractor must be active at the same time as the head to give rise to errors. Using possessors attached at different heights within the same window, we are able to empirically distinguish these accounts. Possessors also allow us to explore two additional issues. First, case marking of local nouns has been shown to reduce agreement errors in languages with "rich" inflectional systems, and we explore whether English speakers attend to case. Secondly, formal syntactic analyses differ regarding the structural position of the possessive marker, and we distinguish them empirically with the relative magnitude of errors produced by possessors and local nouns. Our results show that, across the board, plural possessors are significantly less disruptive to the agreement process than plural local nouns. Proximity to the head noun matters: a possessor directly modifying the head noun induce a significant number of errors, but a possessor within a modifying prepositional phrase did not, though the local noun did. These findings suggest that proximity to a head noun is independent of a "processing window" effect. They also support a noun phrase-internal, case-like analysis of the structural position of the possessive ending and show that even speakers of inflectionally impoverished languages like English are sensitive to morphophonological case-like marking.


Biomarkers of oxidative stress and cataract. Novel drug delivery therapeutic strategies targeting telomere reduction and the expression of telomerase activity in the lens epithelial cells with N-acetylcarnosine lubricant eye drops: anti-cataract which helps to prevent and treat cataracts in the eyes of dogs and other animals.
Cataracts in small animals are shown to be at least partially caused by oxidative damage to lens epithelial cells (LECs) and the internal lens; biomarkers of oxidative stress in the lens are considered as general biomarkers for life expectancy in the canine and other animals. Telomeres lengths and expressed telomerase activity in canine LECs may serve as important monitors of oxidative damage in normal LECs with documented higher levels of telomerase activity in cataractous LECs during cells' lifespan. Loss of functional telomere length below a critical threshold in LECs of canines during the effect of UV and chronic oxidative stress or metabolic failure, can activate programs leading to LEC senescence or death. Telomerase is induced in LECs of canines at critical stages of cataractogenesis initiation and exposure to oxidative stress through the involvement of catalytically active prooxidant transition metal (iron) ions. This work documents that transition metal ions (such as, ferrous ions- catalytic oxidants) might induce premature senescence in LECs of canines, telomere shortening with increased telomerase activity as adaptive response to UV light, oxidative and metabolic stresses. The therapeutic treatment with 1% N-acetylcarnosine (NAC) prodrug delivery is beneficial for prevention and dissolution of ripe cataracts in canines. This biological activity is based on the findings of ferroxidase activity pertinent to the dipeptide carnosine released ophthalmically from NAC prodrug of L-carnosine, stabilizing properties of carnosine on biological membranes based on the ability of the imidazole-containing dipeptides to interact with lipid peroxidation products and reactive oxygen species (ROS), to prevent membrane damage and delute the associated with membrane fragements protein aggregates. The advent of therapeutic treatment of cataracts in canines with N-acetylcarnosine lubricant eye drops through targeting the prevention of loss of functional telomere length below a critical threshold and "flirting" with an indirect effect with telomerase expression in LECs of canines during the effects of UV, chronic oxidative stress increases the successful rate of cataract management challenges in home veterinary care.


[High blood pressure prevalence in Oporto sedentary and regular exercise practicing people].
The association between the lack of exercise and prevalence of high blood pressure (HBP) is a well known fact. The non-pharmacological treatment for HBP includes regular aerobic exercise practicing. A total of 900 individuals, aged above 40, resident in Oporto, representing the 15 parishes of the city, were approached to answer a questionnaire about exercise habits and diagnosis of HBP. The exercise practitioner was defined as the one who practices aerobic exercise for a minimal period of 30 minutes at least 3 times a week. For data analysis non-parametric tests (Pearson's Chi-Square) were used through the Statistical Package for the Social Sciences (SPSS) software. The HBP prevalence in the sample was 39.67% (Confidence Interval (IC) 95%, 36,46% to 42,87%). The HBP prevalence in the exercise practitioners was inferior to the one of the non-practitioners (13,78% vs 25,89%, p < 0,001). This result is valid to the male 33,5% vs 51,6%, p < 0,001) and female population (27,1% vs 51,9%, p < 0,001), as well as to the population without the most frequent HBP-related comorbidities (21,8% vs 44,6%, p < 0,001). The HBP prevalence in the population resident in Oporto city is higher in the non-practitioners of regular exercise. The HBP prevalence, in both sexes, is higher in the non-practitioners of exercise. Finally, we can also conclude that the studied comorbidities don't bias the obtained results because the group of individuals who don't have them the HBP prevalence is still higher in the group of sedentary.


Reversal by a specific peptide (diacetyl-alpha gamma-L-diaminobutyryl-D-alanyl-D-alanine) of vancomycin inhibition in intact bacteria and cell-free preparations.
Vancomycin inhibited the growth of Bacillus megaterium, Staphylococcus aureus and Micrococcus lysodeikticus, and in cell-free preparations from B. megaterium it inhibited the formation of mucopeptide and enhanced the accumulation of the lipid intermediate in the biosynthetic pathway. All these inhibitory processes were reversed by the presence of a synthetic peptide analogous to un-cross-linked mucopeptide side chains, namely diacetyl-l-diaminobutyryl-d-alanyl-d-alanine. A considerable amount of vancomycin was found in recovering cells, whether recovery was caused by peptide or took place naturally because a low initial concentration of antibiotic was used. In cell-free preparations pretreated with vancomycin, continued inhibition of mucopeptide synthesis depended on the presence of cell-wall material. This inhibition was also reversible by added peptide.


Growth hormone excess in children with neurofibromatosis type 1-associated and sporadic optic pathway tumors.
To describe the clinical manifestations of growth hormone (GH) excess in children with optic pathway tumors (OPT). Descriptive case series of 5 children with OPT, 3 with associated neurofibromatosis type 1, referred for evaluation of accelerated linear growth. GH excess was evaluated by oral glucose tolerance tests with frequent sampling of GH levels. Precocious puberty was evaluated by basal luteinizing hormone and sex steroid hormone levels. Stimulation testing with leuprolide acetate (20 μg/kg subcutaneously) was conducted in patients with normal baseline testing. All patients had OPT involving both the hypothalamus and optic chiasm. All patients had elevated levels of the growth factor insulin-like growth factor 1 and on stimulation testing demonstrated an inability to suppress GH levels to < 1.0 ng/mL, indicating the presence of unregulated GH secretion. Additionally, all patients displayed biochemical evidence of precocious puberty. GH excess may be an under-recognized occurrence in the setting of neurofibromatosis type 1 and OPT. GH excess in such patients may contribute to continued brain tumor growth. Given the potential adverse consequences of unrestrained GH excess, all children with chiasmal or hypothalamic tumors who have rapid growth should be evaluated for both precocious puberty and GH excess.


Reconceptualizing practice with multilingual children with speech sound disorders: people, practicalities and policy.
The speech and language therapy profession is required to provide services to increasingly multilingual caseloads. Much international research has focused on the challenges of speech and language therapists' (SLTs) practice with multilingual children. To draw on the experience and knowledge of experts in the field to: (1) identify aspirations for practice, (2) propose recommendations for working effectively with multilingual children with speech sound disorders, and (3) reconceptualize understandings of and approaches to practice. Fourteen members of the International Expert Panel on Multilingual Children's Speech met in Cork, Ireland, to discuss SLTs' practice with multilingual children with speech sound disorders. Panel members had worked in 18 countries and spoke nine languages. Transcripts of the 6-h discussion were analysed using Cultural-Historical Activity Theory (CHAT) as a heuristic framework to make visible the reality and complexities of SLTs' practice with multilingual children. Aspirations and recommendations for reconceptualizing approaches to practice with multilingual children with speech sound disorders included: (1) increased training for working with multilingual children, their families, and interpreters, (2) increased training for transcribing speech in many languages, (3) increased time and resources for SLTs working with multilingual children and (4) use of the International Classification of Functioning, Disability and Health (ICF-CY). The reality and complexities of practice identified in this paper highlight that it is not possible to formulate and implement one 'gold standard' method of assessment and intervention for all multilingual children with speech sound disorders. It is possible, however, to underpin practice with a framework that ensures comprehensive assessment, accurate diagnosis and effective intervention. This paper proposes that by working towards the aspirations of the Expert Panel, SLTs can be empowered to facilitate appropriate services for multilingual children regardless of the context in which they live and the languages they speak.


Taurine concentrations in congestive heart failure.
The concentration of taurine in the left ventricular muscle of hearts of patients who died of chronic congestive heart failure was twice that of patients who died of other causes and had no cardiac pathology. There was no corresponding difference in taurine concentrations in aortic tissue between the two groups. Stress-induced hypertension in rats also led to an increase in taurine concentration in the heart, whereas that in skeletal muscle and brain showed no significant alteration when compared to unstressed animals. Spontaneously hypertensive rats, of the Wistar-derived Okamato strain, showed a similar elevation in cardiac taurine compared to age-matched control Wistar rats.


Protein phosphatase 1-dependent bidirectional synaptic plasticity controls ischemic recovery in the adult brain.
Protein kinases and phosphatases can alter the impact of excitotoxicity resulting from ischemia by concurrently modulating apoptotic/survival pathways. Here, we show that protein phosphatase 1 (PP1), known to constrain neuronal signaling and synaptic strength (Mansuy et al., 1998; Morishita et al., 2001), critically regulates neuroprotective pathways in the adult brain. When PP1 is inhibited pharmacologically or genetically, recovery from oxygen/glucose deprivation (OGD) in vitro, or ischemia in vivo is impaired. Furthermore, in vitro, inducing LTP shortly before OGD similarly impairs recovery, an effect that correlates with strong PP1 inhibition. Conversely, inducing LTD before OGD elicits full recovery by preserving PP1 activity, an effect that is abolished by PP1 inhibition. The mechanisms of action of PP1 appear to be coupled with several components of apoptotic pathways, in particular ERK1/2 (extracellular signal-regulated kinase 1/2) whose activation is increased by PP1 inhibition both in vitro and in vivo. Together, these results reveal that the mechanisms of recovery in the adult brain critically involve PP1, and highlight a novel physiological function for long-term potentiation and long-term depression in the control of brain damage and repair.


Resilience among patients across the cancer continuum: diverse perspectives.
Each phase of the cancer experience profoundly affects patients' lives. Much of the literature has focused on negative consequences of cancer; however, the study of resilience may enable providers to promote more positive psychosocial outcomes before, during, and after the cancer experience. The current review describes the ways in which elements of resilience have been defined and studied at each phase of the cancer continuum. Extensive literature searches were conducted to find studies assessing resilience during one or more stages of the adult cancer continuum. For all phases of the cancer continuum, resilience descriptions included preexisting or baseline characteristics, such as demographics and personal attributes (e.g., optimism, social support), mechanisms of adaptation, such as coping and medical experiences (e.g., positive provider communication), as well as psychosocial outcomes, such as growth and quality of life. Promoting resilience is a critical element of patient psychosocial care. Nurses may enable resilience by recognizing and promoting certain baseline characteristics and optimizing mechanisms of adaptation.


Identification of an immunodominant and highly immunopathogenic determinant in the retinal interphotoreceptor retinoid-binding protein (IRBP).
Interphotoreceptor retinoid-binding protein (IRBP), a glycoprotein specific for the retina and pineal gland, induces inflammatory changes in these two organs in immunized animals. We report here on the identification of an immunodominant determinant of bovine IRBP that is highly immunogenic and immunopathogenic in the Lewis rat. The peptide, which comprises the sequence 1169-1191 of bovine IRBP, was shown to be immunodominant by its capacity to stimulate lymphocytes sensitized against whole IRBP. A comparison was made between peptide 1169-1191 and another peptide, 1158-1180, which is nondominant but is immunogenic and immunopathogenic in the Lewis rat. Peptide 1169-1191 was found to be superior in its immunological capacities; the minimal dose of 1169-1191 needed to induce cellular immune response or disease in Lewis rats (0.02-0.1 nmol/rat) is congruent to 1,000 times smaller than that of 1158-1180. In addition, unlike the ocular disease induced by 1158-1180, the disease produced by 1169-1191 resembled that induced by whole IRBP in its kinetics and histopathological features. The immunological activity of 1169-1191 in the Lewis rat was localized to the 10 residues at the COOH terminus; no such activity was exhibited by the truncated peptide 1169-1188, which comprises the 20 residues at the NH2 terminus of the full peptide. The usefulness of this unique experimental system in analyzing the role of immunodominance in peptide immunogenicity and immunopathogenicity is underscored.


Aronia melanocarpa fruit extract exhibits anti-inflammatory activity in human aortic endothelial cells.
Altered expression of cell adhesion molecules (CAMs) has been implicated in a variety of chronic inflammatory conditions, including atherosclerosis. Regulation of adhesion molecule expression by specific redox-sensitive mechanisms has been reported. Additionally, it has been observed that the extract of Aronia melanocarpa (A. Melanocarpa) fruits, rich in polyphenols, exhibits potent anti-oxidant properties and displays cardioprotective activity. Human aortic endothelial cells (HAECs) were pretreated with various concentrations (primarily 50 μg/mL) of Aronia Melanocarpa fruit extract prior to treatment with TNFα (10 ng/mL) for various periods of time. The surface protein and mRNA expression of ICAM-1 and VCAM-1 were determined using flow cytometry and real-time RT-PCR, respectively. Adhesion of peripheral blood mononuclear leucocytes (PBMLs) to TNFα-treated HAECs was evaluated by an adhesion assay. Activation of NF-κB was evaluated by measuring NF-κB p65 phosphorylation using flow cytometry. ROS production was determined by reduction in fluorescent 2',7'-dichlorofluorescein diacetate (DCFH-DA). Tested A. Melanocarpa extract significantly inhibited the expression of ICAM-1 and VCAM-1, attenuated the phosphorylation of NF-κB p65 and decreased intracellular ROS production in TNFα-treated HAECs. We conclude that A. Melanocarpa fruit extract exhibits anti-inflammatory effects in HAECs by inhibiting the expression of endothelial CAMs, activation of NF-κB and production of ROS.


Characterisation of the overlap COPD-asthma phenotype. Focus on physical activity and health status.
Patients with COPD may share some clinical characteristics with asthma sufferers. This phenotypic overlap between COPD and asthma is not yet well characterised. We have analysed data from the EPI-SCAN study, an epidemiological, population-based study in Spain that included 3885 (40 to 80-year-old) subjects in order to investigate the clinical and systemic inflammatory characteristics of COPD patients previously diagnosed with asthma. Generic and COPD-specific quality of life, as well as physical activity, were also assessed through standardised and validated questionnaires. A total of 385 (10.1%) subjects were diagnosed with COPD, 67 (17.4%) being classified with the COPD-asthma overlap phenotype. Such patients were more likely to have dyspnea and wheezing (p<0.001 in both comparisons) and more frequent exacerbations (p<0.001). No differences in systemic inflammatory markers were observed except for lower NOx concentrations in overlap patients (p=0.013). This overlap phenotype significantly worsened specific quality of life (11.1 units on the St. George's Respiratory Questionnaire (SGRQ), 95%CI: 4.88-17.36) and reduced physical activity (3.49 units on the London Chest Activities of Daily Living (LCADL) scale, 95%CI: 1.06-5.94). In this population-based study, 17.4% of the individuals identified with COPD had an overlap COPD-asthma phenotype. This patient subgroup had more dyspnea, wheezing, exacerbations, worse respiratory-specific quality of life, and reduced levels of physical activity. Specific interventions may be required to adequately care for this subgroup of patients.


[Primary cutane manifestation of a precursor-B-lymphoblastic lymphoma in the external ear].
A Non-Hodgkin Lymphoma (NHL) represents nearly three percent of all malignant tumors. Thirty to fourty percent of the lymphomas are located extra-nodal. Within the head and neck region they might occur in the tonsils, tongue base or the sinuses, the larynx and the pharynx. A cutaneous manifestation is rare. We report on an extranodal B-cell-lymphoma of the ear in a young woman. She reported on a piercing of the pinna months before with a subsequent infection. This infection led to the development of a massive ear tumor. Histologic examination resulted in the final diagnosis. In spite of the considerable extent of the lymphoma there was no systemic manifestation and a total remission was induced by chemotherapy before adjuvant radiation.


Analysis of Anti-Cancer and Anti-Inflammatory Properties of 25 High-THC Cannabis Extracts.
Cannabis sativa is one of the oldest cultivated plants. Many of the medicinal properties of cannabis are known, although very few cannabis-based formulations became prescribed drugs. Previous research demonstrated that cannabis varieties are very different in their medicinal properties, likely due to the entourage effect-the synergistic or antagonistic effect of various cannabinoids and terpenes. In this work, we analyzed 25 cannabis extracts containing high levels of delta-9-tetrahydrocannabinol (THC). We used HCC1806 squamous cell carcinoma and demonstrated various degrees of efficiency of the tested extracts, from 66% to 92% of growth inhibition of cancer cells. Inflammation was tested by induction of inflammation with TNF-α/IFN-γ in WI38 human lung fibroblasts. The efficiency of the extracts was tested by analyzing the expression of COX2 and IL6; while some extracts aggravated inflammation by increasing the expression of COX2/IL6 by 2-fold, other extracts decreased inflammation, reducing expression of cytokines by over 5-fold. We next analyzed the level of THC, CBD, CBG and CBN and twenty major terpenes and performed clustering and association analysis between the chemical composition of the extracts and their efficiency in inhibiting cancer growth and curbing inflammation. A positive correlation was found between the presence of terpinene (pval = 0.002) and anti-cancer property; eucalyptol came second, with pval of 0.094. p-cymene and β-myrcene positively correlated with the inhibition of IL6 expression, while camphor correlated negatively. No significant correlation was found for COX2. We then performed a correlation analysis between cannabinoids and terpenes and found a positive correlation for the following pairs: α-pinene vs. CBD, p-cymene vs. CBGA, terpenolene vs. CBGA and isopulegol vs. CBGA. Our work, thus, showed that most of high-THC extracts demonstrate anti-cancer activity, while only certain selected extracts showed anti-inflammatory activity. Presence of certain terpenes, such as terpinene, eucalyptol, cymene, myrcene and camphor, appear to have modulating effects on the activity of cannabinoids.


Medullary catecholaminergic neurons in the normal human brain and in Parkinson's disease.
Parkinson's disease is thought to cause degeneration of melanin-pigmented catecholaminergic neurons throughout the brainstem, but little quantitative information is available on the fate of catecholaminergic neurons associated with the dorsal vagal complex or medullary reticular formation. We therefore examined these neurons in the normal human medulla and in the brains of patients with Parkinson's disease, using both a melanin stain and immunohistochemical methods with an antiserum against tyrosine hydroxylase. The greatest numbers of catecholaminergic neurons in the ventrolateral reticular formation (A1/C1 group) were located in the far rostral medulla, whereas the largest populations of catecholaminergic cells in the dorsal vagal complex (A2/C2 group) were found at the level of the area postrema. No loss of cells was observed in the A1/C1 group in the parkinsonian brains. In contrast, the A2/C2 group showed moderate loss of neurons, most marked at the level of the area postrema. This difference was entirely due to the loss of neurons in the medial component of the A2 group, a population that normally is only lightly pigmented, while the heavily pigmented neurons in the ventral and intermediate components of the A2 complex were unaffected. Parkinson's disease causes degeneration only of selected populations of medullary catecholaminergic neurons, without apparent relationship to the extent of melanin pigmentation.


Short-wavelength infrared tuneable filters on HgCdTe photoconductors.
The design, micro-fabrication, and electronic and optical performance of a tuneable short-wavelength infrared Fabry-Pérot microresonator on a mercury cadmium telluride photoconductor is presented. The maximum processing temperature of 125 degrees C has negligible effect on the electronic and optical performance of photoconductor test structures. Maximum responsivity, effective carrier lifetime and detectivity are 60x103 VW-1, 2x10-5 s and 8x1010 cmHz1/2W-1, respectively. The maximum effective carrier lifetime and specific detectivity are in good agreement with the theoretical maxima. Uncooled device operation is possible since responsivity is observed not to improve with thermo-electric cooling. Spectral tuning of the micro-filters is demonstrated over the wavelength range 1.7 to 2.2 mum using drive voltages up to 8 V, with the full-width-half-maximum of the resonance approximately 100 nm. Membrane deflection can be up to 40% of the cavity width.


Bioaccumulation of polychlorinated biphenyls and organochlorine pesticides in young-of-the-year bluefish (Pomatomus saltatrix) in the vicinity of a Superfund Site in New Bedford Harbor, Massachusetts, and in the adjacent waters.
Spatial gradients of polychlorinated biphenyls (PCBs) and organochlorine pesticides were examined in the young-of-the-year (YOY) bluefish (Pomatomus saltatrix) in the vicinity of a PCB Superfund Site in New Bedford Harbor, Massachusetts, and in the adjacent waters. PCB concentrations in bluefish varied between different locations, and also among fish from a given location. A generally decreasing gradient in PCB concentrations was evident as the bluefish were collected away from the Superfund Site. The average sum of PCB concentrations were highest for bluefish collected in the Upper Harbor between Interstate-195 Bridge and Coggeshall Street Bridge (Upper Harbor), followed by bluefish in Lower Harbor from north of Popes Island Bridge (Lower Harbor), and bluefish from Outer Harbor south of Hurricane Barrier (Outer Harbor). The levels of PCBs in bluefish from Clarks Cove and PCBs in bluefish from Buzzards Bay were similar and lowest among all bluefish specimens analyzed in the present study. Pesticide concentrations were about one order of magnitude or lower than the PCB concentrations, and the gradient of pesticide concentrations generally followed the gradient of PCB concentrations. Some of the commonly detected pesticides in the order of decreasing concentrations included DDTs and metabolites, heptachlor epoxide, endosulfan sulfate, and α-chlordane. Distribution of PCBs and organochlorine pesticides were examined in the tissues of YOY bluefish from Clarks Cove. PCBs and lipids in the brain samples of YOY bluefish were generally numerically greater than PCBs in the liver samples, but these differences were not statistically significant. PCBs and lipids in hypaxial muscle samples were numerically greater than PCBs in epaxial muscle samples, although these two groups of tissues were not statistically different. Despite the higher susceptibility of lighter PCB homologs to geophysical and biogeochemical weathering processes, the relative dominance of lighter homologs in the Upper Harbor and Lower Harbor samples suggested ongoing or recent sources of these lighter PCBs, particularly Aroclor 1242 and Aroclor 1016 in this area. The presence of heavier homologs in the Upper Harbor and Lower Harbor bluefish samples could be attributed to Aroclor 1252 and Aroclor 1254 that were being used in relatively smaller quantities in the manufacture of electrical components in addition to Aroclor 1242 and Aroclor 1016. The concentration of heavier PCB homologs appears to increase in YOY bluefish the further away from the PCB Superfund Site in the Acushnet Estuary the samples were collected. Principal component analyses of PCB 153 normalized concentrations of the individual PCB congeners resulted in two general groupings; a relatively tight group comprised of YOY bluefish from Upper Harbor, Lower Harbor, and Outer Harbor, and a rather loose and more dispersed group comprised of Buzzards Bay bluefish and the tissue samples of bluefish from Clarks Cove. Principal component analyses of major pesticides suggested close groupings of bluefish from Clarks Cove and bluefish from Buzzards Bay. Pesticides in bluefish from Upper Harbor, Lower Harbor, and Outer Harbor formed a loose group, with some bluefish from these locations populating close to Clarks Cove and Buzzards Bay bluefish. Although PCBs have been implicated in various behavioral and health effects in the experimental and field studies, the deleterious effects of chronic exposure to high concentrations of PCBs and the potential for recruitment of New Bedford Harbor YOY bluefish population to the adult stock remains obscure. Adaptive or evolutionary resistance to contaminants have been documented in resident species in some highly contaminated estuaries, however similar responses have not been investigated in the migratory species like bluefish. The results of the present study provide a reference baseline for YOY bluefish for "before-and-after" comparative studies and other toxicological studies for the New Bedford Harbor Superfund Site that is currently being remediated.


Mindfulness Trait Predicts Neurophysiological Reactivity Associated with Negativity Bias: An ERP Study.
This study explored the relationship of mindfulness trait with the early and late stages of affective processing, by examining the two corresponding ERP components, P2 and LPP, collected from twenty-two male Chinese participants with a wide range of meditation experiences. Multiple regression analyses was performed on the mindfulness scores, as measured by CAMS-R, with the subjective affective ratings and ERP data collected during an emotion processing task. The results showed that increased mindfulness scores predicted increased valence ratings of negative stimuli (less negative), as well as increased P2 amplitudes at the frontocentral location for positive compared to negative stimuli. Based on these findings, a plausible mechanism of mindfulness in reducing negativity bias was discussed. Moreover, our results replicated previous findings on the age-related increase of P2 amplitudes at the frontal sites for positive compared to neutral stimuli. Since the locations at which P2 amplitudes were found as associated with age and mindfulness differed, as did the emotional contents of the stimuli being compared, indicating that the effect of age did not confound our findings on mindfulness and the two factors might operate on early affective processing from distinct sources and mechanisms.


HLA-DR expression and differential trafficking of monocyte subsets following low to intermediate risk surgery.
Reduced HLA-DR expression on monocytes has been suggested as a predictive marker of immunosuppression following very high risk surgery, but there are few reports in lower risk surgery. In 32 patients undergoing low to intermediate risk surgery, blood samples were analysed by flow cytometry for HLA-DR expression and numbers in both CD14(high) and CD14(low)CD16+ monocyte subsets. The numbers of CD14(high) monocytes increased at 24 h (mean (SD), 5.0 (2.2) vs 7.6 (3.9) x 10(5) cells.ml(-1); p < 0.01) while CD14(low)CD16+ monocytes decreased (0.68 (0.36) vs 0.44 (0.36) x 10(5) cells.ml(-1); p < 0.01). HLA-DR expression was significantly reduced in both subsets by 24 h (mean (SD) fluorescent intensity 440 (310) vs 160 (130) for CD14(high) and 1000 (410) vs 560 (380) for CD14(low)CD16+ subsets; p < 0.01). This reduction of monocyte HLA-DR expression 24 h following lower risk surgery raises questions about the purported clinical utility of this biomarker as an early predictor of postoperative complications. Our results also suggest that surgery induces significant trafficking (i.e. mobilisation, margination and extravasation) of monocyte subsets, and that monocyte HLA-DR depression is the result of a down-regulatory phenomenon (decreased protein expression on each cell) rather than the differential trafficking of monocyte subsets.


High-resolution spectral information enables phenotyping of leaf epicuticular wax in wheat.
Epicuticular wax (EW) is the first line of defense in plants for protection against biotic and abiotic factors in the environment. In wheat, EW is associated with resilience to heat and drought stress, however, the current limitations on phenotyping EW restrict the integration of this secondary trait into wheat breeding pipelines. In this study we evaluated the use of light reflectance as a proxy for EW load and developed an efficient indirect method for the selection of genotypes with high EW density. Cuticular waxes affect the light that is reflected, absorbed and transmitted by plants. The narrow spectral regions statistically associated with EW overlap with bands linked to photosynthetic radiation (500 nm), carotenoid absorbance (400 nm) and water content (~ 900 nm) in plants. The narrow spectral indices developed predicted 65% (EWI-13) and 44% (EWI-1) of the variation in this trait utilizing single-leaf reflectance. However, the normalized difference indices EWI-4 and EWI-9 improved the phenotyping efficiency with canopy reflectance across all field experimental trials. Indirect selection for EW with EWI-4 and EWI-9 led to a selection efficiency of 70% compared to phenotyping with the chemical method. The regression model EWM-7 integrated eight narrow wavelengths and accurately predicted 71% of the variation in the EW load (mg·dm-2) with leaf reflectance, but under field conditions, a single-wavelength model consistently estimated EW with an average RMSE of 1.24 mg·dm-2 utilizing ground and aerial canopy reflectance. Overall, the indices EWI-1, EWI-13 and the model EWM-7 are reliable tools for indirect selection for EW based on leaf reflectance, and the indices EWI-4, EWI-9 and the model EWM-1 are reliable for selection based on canopy reflectance. However, further research is needed to define how the background effects and geometry of the canopy impact the accuracy of these phenotyping methods.


Molecular structure differences between the antiviral Nucleoside Analogue 5-iodo-2'-deoxyuridine and the natural nucleoside 2'-deoxythymidine using MP2 and DFT methods: conformational analysis, crystal simulations, DNA pairs and possible behaviour.
5-iodo-2'-deoxyuridine Nucleoside Analogue (IUdR) was the first selective antiviral nucleoside against herpes simplex virus type 1 and 2, and it was also a meaningful anticancer drug. Within a full study of this drug and its possible behaviour, previously, a comprehensive theoretical conformational analysis by MP2 and B3LYP was carried out, and all the possible stable structures were determined with full relaxation of all geometrical parameters. The search located 45 stable structures, and in all them, the whole conformational parameters ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], P, [Formula: see text]max) were analyzed as well as the NBO natural atomic charges. Comparisons of the conformers with those of the natural Nucleoside 2'-deoxythymidine (dT) were carried out, and the main differences between IUdR and dT were analyzed. The accuracy of the methods used was probed with the simulation of the X-ray crystal data by a tetramer form. Watson-Crick (WC) IUdR/dT···2'-deoxyadenosine pairs were analyzed for the first time using quantum chemical calculations, as well as the mispairing IUdR/dT···2'-deoxyguanosine. As result, it is observed that IUdR give rises to a slightly stronger WC pair and weaker mispairing than those with dT, therefore deforming slightly the DNA axis and difficulting the growth of the DNA virus and consequently, killing it.


Sutureless vs sutured posterior costal cartilage grafting in laryngotracheal reconstruction in children.
To compare the postoperative course, complication rate, and decannulation rate in children who underwent either sutureless or sutured posterior costal cartilage grafting during laryngotracheal reconstruction (LTR). Retrospective chart review. Tertiary care children's medical center. The study included children who required posterior costal cartilage grafting when undergoing LTR for subglottic stenosis between the years of 2000 and 2009 by the senior author (J.E.M.) and who had adequate records for review. Postoperative complications, including the incidence of graft prolapse, restenosis or reobstruction requiring surgical intervention, and decannulation rate. Forty-nine children who underwent 52 procedures met the inclusion criteria for this study. All patients had grade III acquired subglottic stenosis and underwent double-staged LTR. Twenty procedures were performed with a sutureless posterior graft, and 32 were performed with suture placement. None of the 20 procedures that were performed with a sutureless graft had prolapse of the graft into the airway compared with 2 of 32 prolapsed posterior grafts (6%) that were sutured (P = .52). Eleven of 20 children (55%) with sutureless posterior grafts compared with 24 of 32 children (75%) who underwent sutured posterior grafts required endoscopic surgical intervention for restenosis or reobstruction (P = .22). Decannulation was achieved in 19 of 20 sutureless cases (95%) and in 28 of 30 cases (93%) in which sutures were placed (P = .56) after a single LTR and necessary endoscopic interventions occurring at 6.3 months and 4.9 months, respectfully (P = .42). Sutureless posterior costal cartilage grafting in children with acquired grade III subglottic stenosis is an equally effective and secure technique compared with sutured posterior grafting during double-staged LTR.


A homolog of Drosophila grainy head is essential for epidermal integrity in mice.
The Drosophila cuticle is essential for maintaining the surface barrier defenses of the fly. Integral to cuticle resilience is the transcription factor grainy head, which regulates production of the enzyme required for covalent cross-linking of the cuticular structural components. We report that formation and maintenance of the epidermal barrier in mice are dependent on a mammalian homolog of grainy head, Grainy head-like 3. Mice lacking this factor display defective skin barrier function and deficient wound repair, accompanied by reduced expression of transglutaminase 1, the key enzyme involved in cross-linking the structural components of the superficial epidermis. These findings suggest that the functional mechanisms involving protein cross-linking that maintain the epidermal barrier and induce tissue repair are conserved across 700 million years of evolution.


Uromodulin (Tamm-Horsfall glycoprotein): a renal ligand for lymphokines.
The protein portion of the immunosuppressive glycoprotein uromodulin is identical to the Tamm-Horsfall urinary glycoprotein and is synthesized in the kidney. Evidence that the glycoproteins are the same is based on amino acid sequence identity, immunologic cross-reactivity, and tissue localization to the thick ascending limb of Henle's loop. Nucleic acid sequencing of clones for uromodulin isolated from a complementary DNA bank from human kidney predicts a protein 639 amino acids in length, including a 24--amino acid leader sequence and a cysteine-rich mature protein with eight potential glycosylation sites. Uromodulin and preparations of Tamm-Horsfall glycoprotein bind to recombinant murine interleukin-1 (rIL-1) and human rIL-1 alpha, rIL-1 beta, and recombinant tumor necrosis factor (rTNF). Uromodulin isolated from urine of pregnant women by lectin adherence is more immunosuppressive than material isolated by the original salt-precipitation protocol of Tamm and Horsfall. Immunohistologic studies demonstrate that rIL-1 and rTNF bind to the same area of the human kidney that binds to antiserum specific for uromodulin. Thus, uromodulin (Tamm-Horsfall glycoprotein) may function as a unique renal regulatory glycoprotein that specifically binds to and regulates the circulating activity of a number of potent cytokines, including IL-1 and TNF.


A stem-loop in the 3' untranslated region mediates iron-dependent regulation of transferrin receptor mRNA stability in the cytoplasm.
Expression of the human transferrin receptor (hTR) and its mRNA is strongly induced by iron deprivation. By measuring transcription elongation rates, levels of hTR-specific nuclear RNA, and mRNA half-lives, we found this regulation to occur posttranscriptionally in the cytoplasm. Analysis of hTR cDNA mutants with deletions in the 3' untranslated region revealed the existence of two distinct domains, both of which are essential for regulation in mouse L cells. The regulated phenotype correlates with the presence of a stem-loop structure predicted by a computer algorithm. Expression of point and deletion mutants affecting the stem-loop confirmed the requirement for this secondary structure in regulation. The 3' untranslated region of hTR cDNA was sufficient to confer iron-dependent regulation on another gene.


Monomeric YoeB toxin retains RNase activity but adopts an obligate dimeric form for thermal stability.
Chromosomally-encoded toxin-antitoxin complexes are ubiquitous in bacteria and regulate growth through the release of the toxin component typically in a stress-dependent manner. Type II ribosome-dependent toxins adopt a RelE-family RNase fold and inhibit translation by degrading mRNAs while bound to the ribosome. Here, we present biochemical and structural studies of the Escherichia coli YoeB toxin interacting with both a UAA stop and an AAU sense codon in pre- and post-mRNA cleavage states to provide insights into possible mRNA substrate selection. Both mRNAs undergo minimal changes during the cleavage event in contrast to type II ribosome-dependent RelE toxin. Further, the 16S rRNA decoding site nucleotides that monitor the mRNA in the aminoacyl(A) site adopt different orientations depending upon which toxin is present. Although YoeB is a RelE family member, it is the sole ribosome-dependent toxin that is dimeric. We show that engineered monomeric YoeB is active against mRNAs bound to both the small and large subunit. However, the stability of monomeric YoeB is reduced ∼20°C, consistent with potential YoeB activation during heat shock in E. coli as previously demonstrated. These data provide a molecular basis for the ability of YoeB to function in response to thermal stress.


Oncologic effectiveness of nerve-sparing radical hysterectomy in cervical cancer.
Nerve-sparing radical hysterectomy (NSRH) was introduced with the aim to reduce pelvic dysfunctions related to conventional radical hysterectomy (RH). Here, we sought to assess the effectiveness and safety of NSRH in a relatively large number of the patients of cervical cancer (CC) patients undergoing either primary surgery or neoadjuvant chemotherapy (NACT) followed by surgery. Outcomes of consecutive patients undergoing NSRH and of a historical cohort of patients undergoing conventional RH were retrospectively reviewed. This study included 325 (49.8%) and 327 (50.2%) undergoing NSRH and RH, respectively. Via a multivariable model, nodal status was the only factor predicting for DFS (hazard ratio [HR]=2.09; 95% confidence interval [CI]=1.17-3.73; p=0.01). A trend towards high risk of recurrence was observed for patients affected by locally advanced cervical cancer (LACC) undergoing NACT followed by surgery (HR=2.57; 95% CI=0.95-6.96; p=0.06). Type of surgical procedures (NSRH vs. RH) did not influence risk of recurrence (p=0.47). Similarly, we observed that the execution of NSRH rather than RH had not a detrimental effect on OS (HR=1.19; 95% CI=0.16-9.01; p=0.87). Via multivariable model, no factor directly correlated with OS. No difference in early complication rates was observed between the study groups. Conversely, a significant higher number of late complications was reported in RH versus NSRH groups (p=0.02). Our data suggested that NSRH upholds effectiveness of conventional RH, without increasing recurrence and complication rates but improving pelvic dysfunction rates.


Significance of coliforms and enterococci in fish products.
Coliforms, more recently fecal coliforms, and enterococci are often used to assess the hygienic quality of foods. Although these bacteria serve rather successfully as an index of fecal pollution of water supplies, their usefulness in measuring fecal pollution in foods is less than satisfactory. The ratio and correlation of coliforms and enterococci in fish-fillet and lobster-meat samples led us to conclude that these organisms originated from improperly sanitized working surfaces, where they survive and multiply, and not from fecal pollution. Therefore, the presence of coliforms and enterococci in fish fillets and lobster meat reflects the quality of fish-plant sanitation and not the direct fecal pollution of these products.


The effects of depleted self-control strength on skill-based task performance.
The purpose of this study was to examine the effects of depleted self-control strength on skill-based sports task performance. Sixty-two participants completed the following: a baseline dart-tossing task (20 tosses), with measures of accuracy, reaction time, and myoelectrical activity of the arms taken throughout; a self-control depletion (experimental) or a nondepletion (control) manipulation; and a second round of dart tossing. As hypothesized, participants in the experimental condition had poorer mean accuracy at Round 2 than control condition participants, and a significant decline in accuracy from Round 1 to Round 2. Experimental condition participants also demonstrated poorer consistency in accuracy compared with control condition participants at Round 2 and a significant deterioration in consistency from Round 1 to Round 2. In addition, consistency in reaction time improved significantly for the control group but not for the experimental group. The results of this study provide evidence that ego depletion effects occur in the performance of a skill-based sports task.


A herpesvirus vector for expression of glycosylated membrane antigens: fusion proteins of pseudorabies virus gIII and human immunodeficiency virus type 1 envelope glycoproteins.
We describe experiments using the swine herpesvirus, pseudorabies virus (PRV), as a vector for expression of hybrid membrane protein genes. In particular, we present the construction and analysis of three infectious PRV mutants expressing chimeric viral membrane proteins composed of portions of the PRV envelope glycoprotein gIII and of the human retrovirus, human immunodeficiency virus type 1 (HIV-1), envelope glycoproteins gp120 and gp41. All of the chimeric genes contain the transcription control sequences and the first 157 codons of PRV gIII (known to contain signals sufficient for efficient export of the encoded peptide out of the cell) fused to different regions of the HIV-1 envelope. The mutant viruses express novel glycosylated fusion proteins that are immunoprecipitated by polyvalent sera specific for gIII, as well as acquired immunodeficiency syndrome patient sera. The levels of expression are lower than expected due primarily to instability or altered processing of the hybrid mRNA. We could not detect cleavage of chimeric proteins carrying the gp120-gp41 protease processing site. The use of localization signals contained within herpesvirus membrane proteins to direct chimeric proteins to desired cellular locations is discussed.


Differential effects of FTY720 on the B cell compartment in a mouse model of multiple sclerosis.
MP4-induced experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis (MS), which enables targeted research on B cells, currently much discussed protagonists in MS pathogenesis. Here, we used this model to study the impact of the S1P1 receptor modulator FTY720 (fingolimod) on the autoreactive B cell and antibody response both in the periphery and the central nervous system (CNS). MP4-immunized mice were treated orally with FTY720 for 30 days at the peak of disease or 50 days after EAE onset. The subsequent disease course was monitored and the MP4-specific B cell/antibody response was measured by ELISPOT and ELISA. RNA sequencing was performed to determine any effects on B cell-relevant gene expression. S1P1 receptor expression by peripheral T and B cells, B cell subset distribution in the spleen and B cell infiltration into the CNS were studied by flow cytometry. The formation of B cell aggregates and of tertiary lymphoid organs (TLOs) was evaluated by histology and immunohistochemistry. Potential direct effects of FTY720 on B cell aggregation were studied in vitro. FTY720 significantly attenuated clinical EAE when treatment was initiated at the peak of EAE. While there was a significant reduction in the number of T cells in the blood after FTY720 treatment, B cells were only slightly diminished. Yet, there was evidence for the modulation of B cell receptor-mediated signaling upon FTY720 treatment. In addition, we detected a significant increase in the percentage of B220+ B cells in the spleen both in acute and chronic EAE. Whereas acute treatment completely abrogated B cell aggregate formation in the CNS, the numbers of infiltrating B cells and plasma cells were comparable between vehicle- and FTY720-treated mice. In addition, there was no effect on already developed aggregates in chronic EAE. In vitro B cell aggregation assays suggested the absence of a direct effect of FTY720 on B cell aggregation. However, FTY720 impacted the evolution of B cell aggregates into TLOs. The data suggest differential effects of FTY720 on the B cell compartment in MP4-induced EAE.


Histologic Healing Rates of Medical Therapies for Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Histologic remission is a potentially valuable means of assessing disease activity and treatment response in ulcerative colitis (UC). However, the efficacy of existing therapies to achieve this outcome is unclear. We performed a systematic review and meta-analysis of histologic outcomes in UC randomized controlled trials and examined the relationship between histologic and endoscopic outcomes. MEDLINE, EMBASE, CENTRAL, and the Cochrane IBD Register were searched for randomized controlled trials of aminosalicylates, corticosteroids, immunosuppressives, biologics, and small molecules. Histologic and endoscopic remission and response data were independently extracted and pooled using binomial-normal random-effect or fixed-effect models. Pooled efficacy estimates were calculated as risk ratios (RRs) using the Mantel-Haenszel method. Univariable and multivariable random-effect meta-regression models examined factors associated with histologic remission. Seventy-four studies (68 induction and 7 maintenance) were identified. Topical aminosalicylate enemas [37.2%, 95% confidence interval (CI), 29.0-46.3] and suppositories (44.9%, 95% CI, 28.9-62.3) had the highest induction of histologic remission rates. Aminosalicylate enemas (RR = 4.14, 95% CI, 2.35-7.31), aminosalicylate suppositories (RR = 3.94, 95% CI, 1.26-12.32), and budesonide multimatrix (RR = 1.47, 95% CI 1.08-1.99) had higher histologic remission rates than placebo. Data were lacking for biologics and immunosuppressives. The pooled histologic remission rate for placebo in induction studies was 10.4% (95% CI, 7.1-15.2). Histologic and endoscopic remission correlated strongly (r = 0.66; 95% CI, 0.50-0.78). In multivariate analysis of placebo-arm data, less severe clinical disease activity and corticosteroid use were associated with higher histologic remission rates. Similarly, mild clinical disease activity was associated with higher histologic remission rates when active-arm data were analyzed. Histologic remission rates for current UC treatments ranged from 15.0% to 44.9% according to drug class and patient population with the highest rates observed for topical aminosalicylates. Placebo remission rates were low with relatively narrow CIs. These data provide benchmarks to inform future trial design. Histologic remission is a potential treatment target in clinical practice.


Vitamin E for the treatment of children with hepatitis B e antigen-positive chronic hepatitis: A systematic review and meta-analysis.
To assess vitamin E efficacy, defined as its ability to induce hepatitis B e antigen (HBeAg) seroconversion, in children with HBeAg-positive persistent hepatitis. In July 2016, we extracted articles published in MEDLINE and the Cochrane Library using the following search terms: "chronic hepatitis B", "children", "childhood", "therapy", "treatment", "vitamin E", "tocopherols", "tocotrienols". Only randomized controlled trials (RCTs) published in English language were collected. Three RCTs met inclusion criteria and were considered in the present meta-analysis. Overall, 23/122 children in the treatment group underwent HBeAg seroconversion vs 3/74 in the control group (OR = 3.96, 95%CI: 1.18-13.25, P = 0.025). Although our meta-analysis has several limits, including the very small number of available studies and enrolled children with HBeAg positivity-related hepatitis, it suggests that vitamin E use may enhance the probability to induce HBeAg seroconversion in these patients. Further well designed and adequately sized trials are required to confirm or deny these very preliminary results.


A nonstationary model of newborn EEG.
The detection of seizure in the newborn is a critical aspect of neurological research. Current automatic detection techniques are difficult to assess due to the problems associated with acquiring and labelling newborn electroencephalogram (EEG) data. A realistic model for newborn EEG would allow confident development, assessment and comparison of these detection techniques. This paper presents a model for newborn EEG that accounts for its self-similar and nonstationary nature. The model consists of background and seizure submodels. The newborn EEG background model is based on the short-time power spectrum with a time-varying power law. The relationship between the fractal dimension and the power law of a power spectrum is utilized for accurate estimation of the short-time power law exponent. The newborn EEG seizure model is based on a well-known time-frequency signal model. This model addresses all significant time-frequency characteristics of newborn EEG seizure which include; multiple components or harmonics, piecewise linear instantaneous frequency laws and harmonic amplitude modulation. Estimates of the parameters of both models are shown to be random and are modelled using the data from a total of 500 background epochs and 204 seizure epochs. The newborn EEG background and seizure models are validated against real newborn EEG data using the correlation coefficient. The results show that the output of the proposed models have a higher correlation with real newborn EEG than currently accepted models (a 10% and 38% improvement for background and seizure models, respectively).


Positional cloning of Sorcs1, a type 2 diabetes quantitative trait locus.
We previously mapped the type 2 diabetes mellitus-2 locus (T2dm2), which affects fasting insulin levels, to distal chromosome 19 in a leptin-deficient obese F2 intercross derived from C57BL/6 (B6) and BTBR T+ tf/J (BTBR) mice. Introgression of a 7-Mb segment of the B6 chromosome 19 into the BTBR background (strain 1339A) replicated the reduced insulin linked to T2dm2. The 1339A mice have markedly impaired insulin secretion in vivo and disrupted islet morphology. We used subcongenic strains derived from 1339A to localize the T2dm2 quantitative trait locus (QTL) to a 242-kb segment comprising the promoter, first exon and most of the first intron of the Sorcs1 gene. This was the only gene in the 1339A strain for which we detected amino acid substitutions and expression level differences between mice carrying B6 and BTBR alleles of this insert, thereby identifying variation within the Sorcs1 gene as underlying the phenotype associated with the T2dm2 locus. SorCS1 binds platelet-derived growth factor, a growth factor crucial for pericyte recruitment to the microvasculature, and may thus have a role in expanding or maintaining the islet vasculature. Our identification of the Sorcs1 gene provides insight into the pathway underlying the pathophysiology of obesity-induced type 2 diabetes mellitus.


When left is not right: handedness effects on learning object-manipulation words using pictures with left- or right-handed first-person perspectives.
According to the body-specificity hypothesis, hearing action words creates body-specific mental simulations of the actions. Handedness should, therefore, affect mental simulations. Given that pictures of actions also evoke mental simulations and often accompany words to be learned, would pictures that mismatch the mental simulation of words negatively affect learning? We investigated effects of pictures with a left-handed, right-handed, or bimanual perspective on left- and right-handers' learning of object-manipulation words in an artificial language. Right-handers recalled fewer definitions of words learned with a corresponding left-handed-perspective picture than with a right-handed-perspective picture. For left-handers, there was no effect of perspective. These findings suggest that mismatches between pictures and mental simulations evoked by hearing action words can negatively affect right-handers' learning. Left-handers, who encounter the right-handed perspective frequently, could presumably overcome the lack of motor experience with visual experience and, therefore, not be influenced by picture perspective.


Is there any relationship between red blood cell distribution width and prognosis of brain death?
Accumulating evidence has demonstrated that RDW (red blood cell distribution width) may independently predict clinically important outcomes in many populations. However, the role of RDW has not been elucidated in brain death. We conducted this study with the aim of evaluating the predictive value of RDW in brain death. A retrospective study of seventy-seven of brain death cases during 36 months were evaluated at university hospitals, affiliated in Tehran, Iran. Demographical data include age, sex, BMI and cause of brain death, also laboratory results (red blood cell distribution, mean corpuscular volume, hemoglobin) collected by checklists from patient records. Having the three RDW measurements (days of hospital admission, day of brain death, and day of cardiac arrest) required. Time interval from hospital admission until brain death was 5.27±4.07. The mean age of brain death cases was 32.65±16.53. The mean RDW values on days of hospital admission, the day of brain death, and the day of cardiac arrest were 14.53±1.98, 15.12±1.93 and 15.18±2.07, respectively. Results of the repeated-measures ANOVA test reveal that RDW level was constantly higher in the traumatic patient group compared to the non-traumatic ones (P=0.008). The frequency of brain death was high in patients with high RDW values. RDW might be a prognostic biomarker for brain death. More prospective studies with large sample size and long follow-up period should be carried out to determine the prognostic significance of RDW and brain death in future.


Visualization studies on evidence-based medicine domain knowledge (series 2): structural diagrams of author networks.
To investigate the output of evidence-based medicine (EBM) researchers in China and elsewhere by examining the EBM domains they work within and the networks that exist among them; using visualization methods to analyze these relationships. This maps the current situation and helps with the identification of areas for future growth. We used co-citation matrixes with Pathfinder networks and hierarchical clustering algorithms, and constructed a co-author matrix which were analyzed with a whole network approach. The analyzed matrixes were visualized with the UCINET program. Much of the development of EBM has been centered around three authors, David Sackett, Gordon Guyatt and L Manchikanti, within three different clusters. The main authors of EBM articles in China were divided into nine academic domains. The relations among core authors of articles indexed by the Science Citation Index (SCI) was loose. There was a stronger co-authorship network among core authors in the Chinese literature, with three groups and 21 cliques. Nine distinct academic communities appeared to have formed around Li Youping, Liu Ming and Zhang Mingming. The EBM literature contains several key clusters, with universities in high-income countries being the source of the majority of articles. Outside China, McMaster University in Canada, the original home of EBM, is the dominant producer of EBM publications. In China, Sichuan University is the main source of EBM publications. The EBM cooperation network in China is comprised of three major groups, the largest and most productive in this sample is led by Li Youping with Liu Ming, Zhang Mingming, Li Jing, Wang Li, Wu Taixiang, and Liu Guanjian as central members.


Acceptability and feasibility of a brief substance use intervention for adolescents in Cape Town, South Africa: A pilot study.
Substance use is prevalent among South African adolescents, but few interventions exist to reduce risk of harm. This study assesses the feasibility, acceptability and preliminary effects of a brief intervention for reducing adolescent substance use and other risk behaviours. This single-arm feasibility test recruited 30 substance-using adolescents and their primary caregiver. Participants received separate interventions (2 sessions for adolescents, 1 session for caregivers), with a subsample randomly selected for post-intervention interviews. Feasibility was measured by the proportion of eligible adolescents who were enrolled and retained in the study. Interviews explored acceptability, and changes in outcomes from baseline to 1-month follow-up assessed preliminary effects of the intervention. Thirty of 43 (69.8%) eligible adolescents and their caregivers were enrolled, with 29 adolescents (96.7%) and 28 caregivers (93.3%) completing the intervention. Twenty-eight adolescents (93.3%) and 29 caregivers (96.7%) were retained at follow-up. Frequency of alcohol, cannabis use and delinquent-type behaviours decreased significantly from baseline to follow-up. Participants appreciated the intervention content and delivery and felt that it facilitated behaviour change. Suggestions for improving the intervention were provided. This study found that the intervention is feasible, acceptable and had promising effects on adolescent behaviour. Efficacy must be established with a randomised controlled trial.


GelSight: High-Resolution Robot Tactile Sensors for Estimating Geometry and Force.
Tactile sensing is an important perception mode for robots, but the existing tactile technologies have multiple limitations. What kind of tactile information robots need, and how to use the information, remain open questions. We believe a soft sensor surface and high-resolution sensing of geometry should be important components of a competent tactile sensor. In this paper, we discuss the development of a vision-based optical tactile sensor, GelSight. Unlike the traditional tactile sensors which measure contact force, GelSight basically measures geometry, with very high spatial resolution. The sensor has a contact surface of soft elastomer, and it directly measures its deformation, both vertical and lateral, which corresponds to the exact object shape and the tension on the contact surface. The contact force, and slip can be inferred from the sensor's deformation as well. Particularly, we focus on the hardware and software that support GelSight's application on robot hands. This paper reviews the development of GelSight, with the emphasis in the sensing principle and sensor design. We introduce the design of the sensor's optical system, the algorithm for shape, force and slip measurement, and the hardware designs and fabrication of different sensor versions. We also show the experimental evaluation on the GelSight's performance on geometry and force measurement. With the high-resolution measurement of shape and contact force, the sensor has successfully assisted multiple robotic tasks, including material perception or recognition and in-hand localization for robot manipulation.


Plasticity Beyond V1: Reinforcement of Motion Perception upon Binocular Central Retinal Lesions in Adulthood.
Induction of a central retinal lesion in both eyes of adult mammals is a model for macular degeneration and leads to retinotopic map reorganization in the primary visual cortex (V1). Here we characterized the spatiotemporal dynamics of molecular activity levels in the central and peripheral representation of five higher-order visual areas, V2/18, V3/19, V4/21a,V5/PMLS, area 7, and V1/17, in adult cats with central 10° retinal lesions (both sexes), by means of real-time PCR for the neuronal activity reporter gene zif268. The lesions elicited a similar, permanent reduction in activity in the center of the lesion projection zone of area V1/17, V2/18, V3/19, and V4/21a, but not in the motion-driven V5/PMLS, which instead displayed an increase in molecular activity at 3 months postlesion, independent of visual field coordinates. Also area 7 only displayed decreased activity in its LPZ in the first weeks postlesion and increased activities in its periphery from 1 month onward. Therefore we examined the impact of central vision loss on motion perception using random dot kinematograms to test the capacity for form from motion detection based on direction and velocity cues. We revealed that the central retinal lesions either do not impair motion detection or even result in better performance, specifically when motion discrimination was based on velocity discrimination. In conclusion, we propose that central retinal damage leads to enhanced peripheral vision by sensitizing the visual system for motion processing relying on feedback from V5/PMLS and area 7.SIGNIFICANCE STATEMENT Central retinal lesions, a model for macular degeneration, result in functional reorganization of the primary visual cortex. Examining the level of cortical reactivation with the molecular activity marker zif268 revealed reorganization in visual areas outside V1. Retinotopic lesion projection zones typically display an initial depression in zif268 expression, followed by partial recovery with postlesion time. Only the motion-sensitive area V5/PMLS shows no decrease, and even a significant activity increase at 3 months post-retinal lesion. Behavioral tests of motion perception found no impairment and even better sensitivity to higher random dot stimulus velocities. We demonstrate that the loss of central vision induces functional mobilization of motion-sensitive visual cortex, resulting in enhanced perception of moving stimuli.


Manganese is critical for antitumor immune responses via cGAS-STING and improves the efficacy of clinical immunotherapy.
CD8+ T cell-mediated cancer clearance is often suppressed by the interaction between inhibitory molecules like PD-1 and PD-L1, an interaction acts like brakes to prevent T cell overreaction under normal conditions but is exploited by tumor cells to escape the immune surveillance. Immune checkpoint inhibitors have revolutionized cancer therapeutics by removing such brakes. Unfortunately, only a minority of cancer patients respond to immunotherapies presumably due to inadequate immunity. Antitumor immunity depends on the activation of the cGAS-STING pathway, as STING-deficient mice fail to stimulate tumor-infiltrating dendritic cells (DCs) to activate CD8+ T cells. STING agonists also enhance natural killer (NK) cells to mediate the clearance of CD8+ T cell-resistant tumors. Therefore STING agonists have been intensively sought after. We previously discovered that manganese (Mn) is indispensable for the host defense against cytosolic dsDNA by activating cGAS-STING. Here we report that Mn is also essential in innate immune sensing of tumors and enhances adaptive immune responses against tumors. Mn-insufficient mice had significantly enhanced tumor growth and metastasis, with greatly reduced tumor-infiltrating CD8+ T cells. Mechanically, Mn2+ promoted DC and macrophage maturation and tumor-specific antigen presentation, augmented CD8+ T cell differentiation, activation and NK cell activation, and increased memory CD8+ T cells. Combining Mn2+ with immune checkpoint inhibition synergistically boosted antitumor efficacies and reduced the anti-PD-1 antibody dosage required in mice. Importantly, a completed phase 1 clinical trial with the combined regimen of Mn2+ and anti-PD-1 antibody showed promising efficacy, exhibiting type I IFN induction, manageable safety and revived responses to immunotherapy in most patients with advanced metastatic solid tumors. We propose that this combination strategy warrants further clinical translation.


Cancer, aging and cellular senescence.
Normal cells do not divide indefinitely due to a process termed cellular or replicative senescence. Several lines of evidence suggest that replicative senescence evolved to protect higher eukaryotes, particularly mammals, from developing cancer. Senescent cells differ from their presenescent counterparts in three way: 1) they arrest growth and cannot be stimulated to reenter the cell cycle by physiological mitogens; 2) they become resistant to apoptotic cell death; 3) they acquire altered differentiated functions. Replicative senescence occurs because, owing to the biochemistry of DNA replication, cells acquire one or more critically short telomere. The mechanism by which a short telomere induces the senescent phenotype is unknown. Recent findings suggest that certain types of DNA damage and inappropriate mitogenic signals can also cause cells to adopt a senescent phenotype. Thus, cells respond to a number of potentially oncogenic stimuli by adopting a senescent phenotype. These findings suggest that the senescence response is a fail-safe mechanism that protects cells from tumorigenic transformation. Despite the protection from cancer conveyed by cellular senescence and other mechanisms that suppress tumorigenesis, the development of cancer is almost inevitable as mammalian organisms age. Why is this the case? Certainly, aging predisposes cells to accumulate mutations, several of which are necessary before malignant transformation occurs, particularly in humans. However, many benign or relatively well-controlled tumors may also harbor many potentially oncogenic mutations, suggesting that the tissue microenvironment can suppress the expression of many malignant phenotypes. Although the idea remains controversial, cellular senescence has also been proposed to contribute to organismal aging. Senescent cells have recently been shown to accumulate with age in human tissues. One possibility is that the tissue microenvironment is disrupted by the accumulation of dysfunctional senescent cells. Thus, mutation accumulation may synergize with the accumulation of senescent cells, leading to increasing risk for developing cancer that is a hallmark of mammalian aging.


Variations of the accessory nerve: anatomical study including previously undocumented findings-expanding our misunderstanding of this nerve.
The anatomy of the accessory nerve has been well described but continued new clinical and anatomical findings exemplify our lack of a full understanding of the course of this nerve. Therefore, this study aimed to expand on our knowledge of the course of the 11th cranial nerve via anatomical dissections. Fifty-six cadavers (112 sides) underwent dissection of the accessory nerve from its cranial and spinal origins to its emergence into the posterior cervical triangle. Immunohistochemistry was performed when appropriate. Our findings included two cases (1.8%) where the nerve was duplicated, one intracranially and one extracranially. One accessory nerve (0.9%) was found to enter its own dural compartment within the jugular foramen. The majority of sides (80%) were found to have a cranial root of the accessory nerve. Thirty-one sides (28%) had connections to cervical dorsal roots medially and three sides (2.7%) laterally. Medial connections were most common with the C1 nerve. Medial components of these dorsal root connections were all sensory in nature. However, lateral components were motor on two sides (1.8%). Nerves traveled anterior to the internal jugular vein on 88% of sides. One (0.9%) left side nerve joined an interneural anastomosis between the dorsal rootlets. Macroganglia were found on the spinal part of the intracranial nerve on 13% of sides. The lesser occipital nerve arose directly from the accessory nerve on two sides (1.8%) and communicated with the accessory nerve on 5.4% of sides. One side (0.9%) was found to communicate with the facial nerve with both nerves innervating the sternocleidomastoid muscle. Additional anatomical knowledge of the variants of the accessory nerve may benefit patient care when this nerve is pathologically involved.


Pharmacokinetics and pharmacodynamics of acepromazine in horses.
A specific, sensitive, reverse-phase high-performance liquid chromatographic assay for acepromazine, with analytic sensitivity as low as 5 ng/ml of plasma, and electrochemical detection with an oxidation potential of 0.7 V, was used to study the pharmacokinetics of acepromazine given at a dosage of 0.15 mg/kg of body weight in horses. The relation between effect and pharmacokinetics of the drug was examined. The effects studied included those on blood pressure, pulse, PCV, measures of respiration function, and sedation. Intravenously administered doses led to a biphasic concentration decay pattern with an alpha-phase distribution half-life of < 3 minutes. The beta-phase half-life was in the range of 50 to 150 minutes. The CNS effects peaked at 20 minutes after administration, and the hemodynamic effects peaked at 100 minutes. In all horses, the most sensitive variable was the PCV, which decreased by up to 20% (P < 0.0001). Systolic, diastolic, and mean blood pressures decreased (P < 0.0001); heart rate was unchanged (P > 0.05). Neither blood gas tensions nor blood pH changed noticeably (P > 0.05). In all horses studied, acepromazine had a significant (P < 0.0001) sedative effect, as observed by posture and alertness. None of the observed pharmacodynamic effects correlated well with plasma acepromazine concentration. These effects persisted beyond the time of detectable acepromazine concentration, indicating that they might be caused by active metabolites, or that their timing could result from complex pharmacokinetic compartment influences.


Patient characteristics and patterns of use for lumbar spine radiographs: results from the Veterans Health Study.
Longitudinal data from the Veterans Health Study, an observational study of male patients receiving Veterans Administration ambulatory care, were analyzed. To identify patient characteristics that predict different patterns in the use of lumbar spine radiographs. In this study, 401 patients with low back pain receiving ambulatory care services in four Veterans Administration outpatient clinics in the greater Boston area were followed for 12 months. Participants were mailed the Medical Outcome Study Short Form Health Survey and participated in scheduled interviews that included the completion of a low back questionnaire, a comorbidity index, and a straight leg raising test. Four groups of patients were defined according to the patterns of use for lumbar spine radiographs: prior use, repeat use, no use, and new use of lumbar spine radiographs. These groups were compared in terms of sociodemographics, comorbid conditions, low back pain intensity, radiating leg pain, straight leg raising, Medical Outcome Study Short Form Health Survey scores, and low back disability days. The patients with new lumbar spine radiographs showed worse physical and psychological distress than the participants in the other three groups. In contrast, the patients with no lumbar spine radiographs reported minor physical impairment. Compared with patients who had no repeat radiographs, patients with repeat lumbar spine radiographs had similar scores on physical health, but they showed worse scores of mental health. Both physical and psychological factors contribute to having new radiographic examinations, whereas psychological factors have increased importance in the repeat use of roentgenographic examinations. Repeat radiographs appear to be overused, judging by the severity of physical impairment as measured by low back pain intensity, the Medical OutcomeStudy Short Form Health Survey, and disability days.


Radiographic evaluation of conical tapered platform-switched implants in the posterior mandible: 1-year results of a two-center prospective study.
Long-term success of dental implants depends on healthy peri-implant soft tissues and adequate bone levels. This prospective study aims to assess bone level changes around implants with internal conical connection and platform-switching abutments in the posterior mandible. Adult patients missing at least two teeth in the posterior mandible and with a natural tooth mesial to the implant site received two or three adjacent internal conical connection implants. After a minimum transmucosal healing period of 8 weeks, single crown restorations were cemented over platform-switching abutments. Changes in marginal bone levels were measured in standardized periapical radiographs from surgery and loading (baseline) to 12 months post-loading. Twenty-four patients received 52 implants. Bone remodeling took place between surgery and loading (-0.53 ± 0.40 mm). From loading to 12 months, there was a mean bone gain of 0.12 ± 0.42 mm which occurred mainly in the first 6 months after prosthesis delivery (0.11 ± 0.36 mm) and stabilized afterward. A total of 71.7% of all implants presented bone preservation or gain. No implant was lost at 1 year and the success rate was 100%. Patient inquiry revealed high satisfaction. Internal conical connection implants with platform-switching abutments presented high success rate and enhancement or preservation of marginal bone levels after 1 year of loading.


Risk factors for trichomoniasis among women with human immunodeficiency virus (HIV) infection at a public clinic in Los Angeles County, California: implications for HIV prevention.
Persons with human immunodeficiency virus (HIV) infection who subsequently develop an acute sexually transmitted disease have an increased probability of transmitting HIV. Therefore, characterizing such persons can help direct prevention efforts to a group who are likely to be continuing sources of HIV transmission. We assessed the incidence and factors associated with trichomoniasis in a cohort of HIV-infected women receiving care at a public clinic in Los Angeles County, California from 1992 through 1995. Demographic, clinical, and behavioral data were available from medical records and from patient interviews. Trichomonas infection was the most frequently identified sexually transmitted disease and was found in 37 (17.4%) of 212 women representing a crude incidence rate of 14.1 per 100 person-years experience. The crude rate of trichomoniasis was highest in black women (69.0 per 100 person-years), women with a history of trading sex for drugs or money (51.0 per 100 person-years), those using crack or cocaine (35.5 per 100 person-years), women with four or more sex partners (43.0 per 100 person years), and those born in the United States (23.3 per 100 person-years). Among women with severe immunosuppression (CD4+ count < 200), 18.4% (18 of 98) were diagnosed with trichomoniasis. After multivariate analysis using a Cox proportional hazards approach, black race (adjusted rate ratio [RR] = 5.6, 95% confidence interval [CI] = 2.3, 13.3) continued to be strongly associated with Trichomonas infection. Trading sex for money or drugs (adjusted RR = 25.2, 95% CI = 4.3, 148.6) and single marital status (adjusted RR = 3.7, 95% CI = 1.1, 13.0) were independent risk factors for trichomoniasis in nonblack women but not among black women. Data from this study indicate that Trichomonas may be a frequently acquired infection in HIV-positive women. Our findings suggest that HIV-infected women who are black, and nonblack women who trade sex for money or drugs or are unmarried, are at increased risk of trichomoniasis and therefore may be more likely to transmit HIV infection. Local HIV prevention strategies should target such women for intervention efforts.


Episodic long-term memory of spoken discourse masked by speech: what is the role for working memory capacity?
To investigate whether working memory capacity (WMC) modulates the effects of to-be-ignored speech on the memory of materials conveyed by to-be-attended speech. Two tasks (reading span, Daneman & Carpenter, 1980; Rönnberg et al., 2008; and size-comparison span, Sörqvist, Ljungberg, & Ljung, 2010) were used to measure individual differences in WMC. Episodic long-term memory of spoken discourse was measured by requesting participants to listen to stories masked either by normal speech or by a rotated version of that speech and to subsequently answer questions on the content of the stories. Normal speech impaired performance on the episodic long-term memory test, and both WMC tasks were negatively related to this effect, indicating that individuals with high WMC are less susceptible to disruption. Moreover, further analyses revealed that size-comparison span (a task that requires resolution of semantic confusion by inhibition processes) is a stronger predictor of the effect than is reading span. Cognitive control processes support listening in adverse conditions. In particular, inhibition processes acting to resolve semantic confusion seem to underlie the relationship between WMC and susceptibility to distraction from masking speech.


Monitoring excess unplanned return to theatre following colorectal cancer surgery.
To develop a risk-adjustment model for unplanned return to theatre (URTT) outcomes following colorectal surgeries in Australia and New Zealand hospitals and apply top-down and bottom-up statistical process control methods for fair comparison of hospitals and surgeons' URTT rates. We analysed URTT outcomes from hospitals contributing data to the Bi-National Colorectal Cancer Audit clinical registry between 2007 and 2016. Preoperative and intraoperative covariates were considered for risk adjustment. A risk-adjusted rate funnel plot was prepared for between-hospital comparisons and identification of outlying hospitals with unusually high rates of URTT. Cumulative observed-minus-expected charts with cumulative sum signals were then presented for surgeons within an outlying hospital. The study included 15 134 patients and 166 surgeons across 70 hospitals. The weighted average URTT rate was 5.2%. The risk-adjustment model identified 12 preoperative and intraoperative variables that significantly raise the risk of URTT: male sex, American Society of Anesthesiologists score, emergency admissions, conversion entry, left hemicolectomy, total colectomy, proctocolectomy, lower anterior resection, ultra-low anterior resection, abdominoperineal resection, organ resection and excess lymph nodes harvested. Right hemicolectomy significantly reduced risk of URTT. URTT rates were not found to significantly vary across seniority of operator; however, comparisons were limited by lack of data on junior operators. The funnel plot identified five hospitals as 'possible outliers' and hospital T was identified as a 'definite outlier'. The cumulative observed-minus-expected charts with cumulative sum signals showed that within hospital T, one surgeon among three had a particularly bad run of URTTs. Feedback from aggregated URTT outcomes using a risk-adjusted rate funnel plot is enhanced when follow-up examination of outlying hospitals is conducted with concurrent application of cumulative observed-minus-expected charts with cumulative sum signals.


Complications of ERCP: a prospective study.
Studies of ERCP-related morbidity seldom include a sufficient patient follow-up. The aim of this study was to characterize and to evaluate the frequency of complications, cardiopulmonary untoward events in particular. All patients undergoing ERCP during a 2-year period were included in this prospective study. Complications were assessed at the time of ERCP and by postal/telephone contact at 30-days after the procedure. A total of 1177 ERCPs were included in the analysis, of which 56.2% were therapeutic. The 30-day complication rate was 15.9%; the procedure-related mortality rate was 1.0%. Post-ERCP pancreatitis occurred in 3.8% of patients (3 deaths). Hemorrhage or perforation occurred with 0.9% and 1.1%, respectively, of the procedures (3 deaths). One perforation that resulted in the death of the patient occurred after placement of an endoprosthesis. Cholangitis occurred in relation to 5% of the ERCP procedures (3 deaths). Cardiorespiratory complications occurred in 2.3% (2 deaths). Dilated bile duct ( p = 0.0001), placement of stent ( p = 0.001), and use of more than 40 mg of hyoscine-N-butyl bromide ( p < 0.05) were risk factors for complications by multivariate analysis. Risk of pancreatitis was increased with age under 40 years ( p = 0.0078), placement of stent ( p = 0.031), and a dilated bile duct ( p = 0.036). This prospective study confirms that the complication rate of ERCP including therapeutic procedures is high. Cardiopulmonary complications were not as common as expected, despite being the special focus of the study.


Analysis of viral diversity for vaccine target discovery.
Viral vaccine target discovery requires understanding the diversity of both the virus and the human immune system. The readily available and rapidly growing pool of viral sequence data in the public domain enable the identification and characterization of immune targets relevant to adaptive immunity. A systematic bioinformatics approach is necessary to facilitate the analysis of such large datasets for selection of potential candidate vaccine targets. This work describes a computational methodology to achieve this analysis, with data of dengue, West Nile, hepatitis A, HIV-1, and influenza A viruses as examples. Our methodology has been implemented as an analytical pipeline that brings significant advancement to the field of reverse vaccinology, enabling systematic screening of known sequence data in nature for identification of vaccine targets. This includes key steps (i) comprehensive and extensive collection of sequence data of viral proteomes (the virome), (ii) data cleaning, (iii) large-scale sequence alignments, (iv) peptide entropy analysis, (v) intra- and inter-species variation analysis of conserved sequences, including human homology analysis, and (vi) functional and immunological relevance analysis. These steps are combined into the pipeline ensuring that a more refined process, as compared to a simple evolutionary conservation analysis, will facilitate a better selection of vaccine targets and their prioritization for subsequent experimental validation.


Surface developmental dyslexia is as prevalent as phonological dyslexia when appropriate control groups are employed.
Previous investigations of the incidence of developmental surface and phonological dyslexia using reading-age-matched control groups have identified many more phonological dyslexics (poor nonword reading relative to irregular-word reading) than surface dyslexics (poor irregular-word reading relative to nonword reading). However, because the measures that have been used to estimate reading age include irregular-word reading ability, they appear inappropriate for assessing the incidence of surface dyslexia. The current study used a novel method for generating control groups whose reading ability was matched to that of the dyslexic sample. The incidence of surface dyslexia was assessed by comparing dyslexic performance with that of a control group who were matched with the dyslexics on a test of nonword reading. The incidence of phonological dyslexia was assessed with reference to a control group who were matched with the dyslexics at irregular-word reading. These control groups led to the identification of an approximately equal number of children with surface and phonological dyslexia. It appeared that selecting control participants who were matched with dyslexics for reading age led to the recruitment of individuals with relatively high nonword reading scores relative to their irregular-word reading scores compared with other types of control group. The theoretical implications of these findings are discussed.


Connectivity Restoration in Wireless Sensor Networks via Space Network Coding.
The problem of finding the number and optimal positions of relay nodes for restoring the network connectivity in partitioned Wireless Sensor Networks (WSNs) is Non-deterministic Polynomial-time hard (NP-hard) and thus heuristic methods are preferred to solve it. This paper proposes a novel polynomial time heuristic algorithm, namely, Relay Placement using Space Network Coding (RPSNC), to solve this problem, where Space Network Coding, also called Space Information Flow (SIF), is a new research paradigm that studies network coding in Euclidean space, in which extra relay nodes can be introduced to reduce the cost of communication. Unlike contemporary schemes that are often based on Minimum Spanning Tree (MST), Euclidean Steiner Minimal Tree (ESMT) or a combination of MST with ESMT, RPSNC is a new min-cost multicast space network coding approach that combines Delaunay triangulation and non-uniform partitioning techniques for generating a number of candidate relay nodes, and then linear programming is applied for choosing the optimal relay nodes and computing their connection links with terminals. Subsequently, an equilibrium method is used to refine the locations of the optimal relay nodes, by moving them to balanced positions. RPSNC can adapt to any density distribution of relay nodes and terminals, as well as any density distribution of terminals. The performance and complexity of RPSNC are analyzed and its performance is validated through simulation experiments.


Effect of a founder event on variation in the genetic sex-determining system of the fire ant Solenopsis invicta.
Effects of a recent founder event on genetic diversity in wild populations of the fire ant Solenopsis invicta were studied, with particular attention given to the genetic sex-determining system. Diploid males are far more common relative to haploid males in introduced populations than in native populations of fire ants, and queens that produce diploid males account for a significantly larger proportion of the mated queens in introduced than in native populations. Differences between native and introduced populations in attributes of the mating systems (i.e., queen mating frequency or level of inbreeding) can be excluded as factors contributing to these different levels of diploid male production. Thus, we conclude that diploid males have increased in frequency in introduced populations because of a loss of allelic diversity at the sex-determining locus (loci). This loss of sex alleles has generated a substantial increase in the estimated segregational genetic load associated with production of sterile diploid males in introduced populations over the load in native populations. The loss of allelic diversity in the sex-determining system in introduced S. invicta is paralleled by a loss of electrophoretically detectable rare alleles at protein-encoding loci. Such concordance between these different types of markers is predicted because each of the many sex alleles present in the native populations is expected to be rare. Estimates of expected heterozygosity (Hexp) based on 76 electrophoretic loci do not differ significantly between the native and introduced fire ant populations, illustrating the lack of sensitivity of this measure for detecting many types of bottlenecks.