Dual deep modeling: multi-level modeling with dual potencies and its formalization in F-Logic.
An enterprise database contains a global, integrated, and consistent representation of a company's data. Multi-level modeling facilitates the definition and maintenance of such an integrated conceptual data model in a dynamic environment of changing data requirements of diverse applications. Multi-level models transcend the traditional separation of class and object with clabjects as the central modeling primitive, which allows for a more flexible and natural representation of many real-world use cases. In deep instantiation, the number of instantiation levels of a clabject or property is indicated by a single potency. Dual deep modeling (DDM) differentiates between source potency and target potency of a property or association and supports the flexible instantiation and refinement of the property by statements connecting clabjects at different modeling levels. DDM comes with multiple generalization of clabjects, subsetting/specialization of properties, and multi-level cardinality constraints. Examples are presented using a UML-style notation for DDM together with UML class and object diagrams for the representation of two-level user views derived from the multi-level model. Syntax and semantics of DDM are formalized and implemented in F-Logic, supporting the modeler with integrity checks and rich query facilities.


EDEL: ENEA DOSEMETER FOR EYE LENS.
Since the publication of International Commission on Radiological Protection statement in 2011 on tissue reaction, eye lens radiation protection played an important role in exposed personnel dosimetry. For this reason, the Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA) Individual Monitoring Service decided to study a prototype to fulfil specific requests (e.g. for survey in interventional department and intercomparisons). On the basis of such preliminary investigation, a new eye lens dosemeter was developed. The new dosemeter, named EDEL (ENEA Dosemeter for Eye Lens), was characterised in terms of Hp(3), the operational quantity related to eye lens monitoring. The investigation was performed experimentally and optimised using the Monte Carlo MCNP6 code. The new prototype was thought to fulfil two main requests: the reliability of the dosimetric data and the portability of the dosemeter itself. The new dosemeter will soon be supplied to the collaborating hospitals for workplace test measurements.


Mycotoxin Contamination of Rice in China.
Mycotoxin contamination in rice is generally lower than in other cereals such as corn or wheat. However, over 65% of the population in China consumes rice as a staple food. Due to the diversity of the climate across China, the southern region is characterized by high temperatures and humidities, especially in rainy season. Such conditions are optimal for the growth of fungi. The accumulative and transferrable characteristics of fungi mycotoxins pose a great potential threat as confirmed by high incidences of liver cancer in the Yangtze delta region. Major mycotoxins identified in China are aflatoxins and ochratoxin A, as well as fumonisins. The contents of aflatoxin B1 (AFB1 ) in rice are varied among different provinces and regions and generally less than 5 μg/kg. Although high incidences of positive aflatoxins samples have widely been detected, few samples were detected as exceeding the national's maximum residue limit (10 μg/kg). Limited information is available on risk assessment of human health hazards of mycotoxins in rice, children should be paid more attention to due to their having the highest mycotoxins exposure level, although the risks are generally at low levels from rice. Mycotoxins are mainly distributed in the outer layer of the paddy rice (also called rough rice, referring to whole rice grain with the hulls), and the AFB1 content in bran is 8.4 times greater than that in brown rice (hulled rice). Further investigation should focus on isolation and identification of mycotoxins-producing fungal strains, especially unknown mycotoxigenic fungal strains determination. Infection resistant rice breeding of mycotoxigenic fungal species may be a fundamental approach to guaranteeing rice safety in China.


What Do We Need to Protect, at All Costs, During the 21st Century? Reflections From a Curated, Interactive Co-Created Intellectual Jazz Performance.
The question that forms the title of this article, "What do we need to protect, at all costs, during the 21st century?," speaks to the sizable changes in health care systems and settings that surround the continuing professional development (CPD) provider, and the need to establish a core set of principles and practices as the field moves forward from both theoretical and practical aspects. It also provided the focus for one of the five keynote lectures presented during the 2016 World Congress on Continuing Professional Development. As the planners of this keynote session, we sought to evoke answers to the question, not from the speaker, but from the audience itself, a process enabled by a highly engaging presentation style and powered by interactive digital technologies. Further, we believed that the session would not directly lead to suggestions to improve the theory and practice of CPD, but rather to create the biopsychosocial context-a sort of platform-on which such discussions can occur.


Evaluation of surgical resection for gallbladder carcinoma at a Japanese cancer institute.
Surgical resection is a radical treatment option for gallbladder carcinoma (GBC); however, it is still difficult to cure and patient prognosis is poor. An assessment of the surgical results and chemotherapy options may elucidate effective treatments. We retrospectively examined the demographics, surgical records and outcome in 33 patients with GBC undergoing surgical resection. Postoperative cancer recurrence was observed in 36% of patients. Mean cancer-free survival time was 84 months and 3-year cancer-free survival rate was 70% Mean overall survival time was 96 months and 5-year overall survival rate was 52%. The 3-year cancer-free survival and the 5-year overall survival were significantly different between the final tumor stages (p<0.001). Higher CEA and CA19- 9 level were significantly related to poor overall survival (p<0.05). Macroscopically, papillary type tumor showed significantly better overall survival compared to nodular or flat types (p<0.05). Degree of invasion, node metastasis, moderate or poor differentiation, vascular or perineural invasion and invasion of the liver or hepatoduodenal ligament were significantly associated with poor overall survival (p<0.05). A cancerfree margin at the hepatic cut end and dissected periductal structures showed a significantly poor prognosis (p<0.05). The overall survival in final curability A was significantly associated with better curability than B or C (p<0.05). Radically extended surgical resection for GBC is necessary to obtain improved patient survival and new adjuvant chemotherapy would be expected to improve results after surgery.


Developing gradient metal alloys through radial deposition additive manufacturing.
Interest in additive manufacturing (AM) has dramatically expanded in the last several years, owing to the paradigm shift that the process provides over conventional manufacturing. Although the vast majority of recent work in AM has focused on three-dimensional printing in polymers, AM techniques for fabricating metal alloys have been available for more than a decade. Here, laser deposition (LD) is used to fabricate multifunctional metal alloys that have a strategically graded composition to alter their mechanical and physical properties. Using the technique in combination with rotational deposition enables fabrication of compositional gradients radially from the center of a sample. A roadmap for developing gradient alloys is presented that uses multi-component phase diagrams as maps for composition selection so as to avoid unwanted phases. Practical applications for the new technology are demonstrated in low-coefficient of thermal expansion radially graded metal inserts for carbon-fiber spacecraft panels.


Exercise training impacts skeletal muscle gene expression related to the kynurenine pathway.
Exercise positively impacts mood and symptoms of depression; however, the mechanisms underlying these effects are not fully understood. Recent evidence highlights a potential role for skeletal muscle-derived transcription factors to influence tryptophan metabolism, along the kynurenine pathway, which has important implications in depression. This has important consequences for older adults, whose age-related muscle deterioration may influence this pathway and may increase their risk for depression. Although exercise training has been shown to improve skeletal muscle mass in older adults, whether this also translates into improvements in transcription factors and metabolites related to the kynurenine pathway has yet to be examined. The aim of the present study was to examine the influence of a 12-wk exercise program on skeletal muscle gene expression of transcription factors, kynurenine aminotransferase (KAT) gene expression, and plasma concentrations of tryptophan metabolites (kynurenines) in healthy older men over 65 yr of age. Exercise training significantly increased skeletal muscle gene expression of transcription factors (peroxisome proliferator-activated receptor-γ coactivator 1α, peroxisome proliferator-activated receptor-α, and peroxisome proliferator-activated receptor-δ: 1.77, 1.99, 2.18-fold increases, respectively, P < 0.01] and KAT isoforms 1-4 (6.5, 2.1, 2.2, and 2.6-fold increases, respectively, P ≤ 0.01). Concentrations of plasma kynurenines were not altered. These results demonstrate that 12 wk of exercise training significantly altered skeletal muscle gene expression of transcription factors and gene expression related to the kynurenine pathway, but not circulating kynurenine metabolites in older men. These findings warrant future research to determine whether distinct exercise modalities or varying intensities could induce a shift in the kynurenine pathway in depressed older adults.


Sound source segregation by goldfish: two simultaneous tones.
The perception of two simultaneous tones was investigated in goldfish using classical respiratory conditioning and a stimulus generalization paradigm. Pairs of tones were used to make up a mixture of 150 Hz and a higher harmonic or a mistuned harmonic. Fish were conditioned to the two-tone mixture and then tested for generalization to several pure tones. The simultaneous tones tended to be segregated in perception, with the generalization gradient for single tones having two peaks corresponding to the frequencies of the tone pairs. There were no consistent differences in the generalization gradients following conditioning to harmonic or inharmonic tone pairs. In addition, experiments were carried out in which the two tones of the pair were heard on alternate trials, always as single tones, followed by generalization tests to single tones. There was more generalization in this experiment, reflecting the fact that conditioning and generalization test stimuli were both single tones. However, the shapes of the generalization gradients were similar to those in which fish were conditioned to two simultaneous tones, indicating that the simultaneity of the tones did not make them harder to segregate. As the frequency separation between the two components narrowed, segregation tended to fail.


Intra-individual variation of serum prostate specific antigen levels in men with benign prostate biopsies.
To determine the intra-individual (physiological) variation of prostate-specific antigen (PSA) measurements in men after a benign prostatic biopsy. Sixty-four men were prospectively assessed, all of whom had a benign prostatic biopsy within the preceding 13 months. The degree of intra-individual variability was established by calculating the coefficient of variation on four PSA levels obtained from each patient weekly over a month. Six patients were subsequently diagnosed with prostate cancer and their data are presented separately. In the remaining 58 patients the median (range) individual mean PSA value was 6.3 (0.5-34.1) ng/mL. The median (range) coefficient of variation within the group was 9.5 (2.4-76.1)%. There was a clear linear relationship between mean PSA level and the standard deviation. In 48 of the 63 patients analysed, the coefficient of variation for serum PSA values in the group as a whole was greater than the variation claimed for the assay technique. The significance of the linear relationship between PSA and the standard deviation is discussed, with particular reference to those men who had a benign prostate biopsy.


Disparities in Risk Factors and Birth Outcomes Among American Indians in North Dakota.
Objectives High infant mortality rates among American Indians in North Dakota contribute to a 20-year gap in average age at death compared to whites. Geographic- and race-specific health disparities data to drive policy making and interventions are not well disseminated. The current study examines prenatal risk factors and birth outcomes between American Indian and whites in North Dakota. Methods A retrospective descriptive analysis of North Dakota live births from 2007 to 2012 was conducted. Period prevalence and prevalence ratios were calculated. Results The infant mortality rate from 2010 to 2012 for infants born to American Indian women was 3.5 times higher than whites. Racial disparities existed in education, teen births, tobacco use during pregnancy, and breastfeeding initiation. Disparities widened for inadequate prenatal care, illegal drug use during pregnancy, and infant mortality from 2007-2009 to 2010-2012 and narrowed for sexually transmitted infections and alcohol use during pregnancy. Conclusions for Practice American Indians are disproportionately affected by poor pregnancy and birth outcomes in North Dakota. Future geographic-specific American Indian research is warranted to aid current and future public health interventions.


Endogenous volatile organic compounds in breath and blood of healthy volunteers: examining breath analysis as a surrogate for blood measurements.
To investigate the premise that levels of endogenous volatile organic compounds (VOC) in breath reflect those in blood, the concentration of acetone and isoprene were measured in radial arterial blood, peripheral venous blood and breath samples from ten healthy volunteers. Coefficients of repeatability as a percentage of mean are less than 30% in breath but greater than 70% in blood. The volunteer-mean ratios of arterial to venous blood concentration are 1.4 (0.9-2.1) for acetone and 0.55 (0.3-1.0) for isoprene. Concentration in breath showed a significant inter-subject correlation with concentration in arterial blood (CAB) for acetone but not for isoprene. Arterial blood/breath ratios are 580 (280-1060) for acetone and 0.47 (0.22-0.77) for isoprene. The sample-mean blood/breath ratio was used to calculate an estimate of CAB and the standard deviation of this estimate was lower than that of arterial blood measured directly. For most subjects, estimated CAB was within uncertainty limits of the actual CAB. Owing to the poor repeatability of VOC concentrations from consecutive blood samples, and the capacitive effects of the lung, this study suggests that breath VOC measurements may provide a more consistent measure than blood measurements for investigating underlying physiological function or pathology within individuals.


A comparison of the binding of endothelin to various tissues from spontaneously hypertensive and Wistar-Kyoto rats.
The binding affinities for endothelin-1 and endothelin-3 to membrane preparations of various tissues of spontaneously hypertensive rats and normotensive Wistar-Kyoto rats were compared by competition binding of the peptides with [(125)I]endothelin-1. Endothelin-1 binding data obtained using membrane preparations from brain, heart, kidney, liver, lung and spleen of both strains were better fit with a one-site model. The brain tissue demonstrated the highest affinity for endothelin-1 in both strains with the same IC(50) of 0.11 nM, while the kidney and lung tissues showed the lowest affinities in both strains with IC(50) values ranged between 1.4 and 4.1 nM. Only the kidney tissues of these two strains showed a statistically significant difference in binding affinities for endothelin-1; the IC(50) values were 1.4 +/- 0.1 nM (mean +/- SE, n = 3) and 3.2 +/- 0.4 nM (n = 4) for the spontaneously hypertensive and normotensive rats, respectively. Endothelin-3 binding data obtained using membrane preparations from brain, kidney and lung of both strains were also better fit with a one-site model. In contrast, a two-site model was more suitable for analyzing endothelin-3 binding results obtained using membrane preparations from heart, liver and spleen of both strains. Again, only the kidney tissues of the two strains showed a statistically significant difference in binding affinities for endothelin-3. The ratio of IC(50) value of the major endothelin-3 binding site to that of endothelin-1 in each tissue varied from approx. 1.5 in brain, kidney and liver to greater than 500 in heart and spleen of both strains. Scatchard analysis of saturation binding data showed that [(125)I]endothelin-1 bound to a single class of binding sites in brain, heart, liver and spleen of both rat strains and in kidney of the spontaneously hypertensive rats. Specific binding to the kidney membrane preparation of the normotensive rats was not saturable at radioligand concentrations up to about 2 nM. These results suggest that the tissues of both strains investigated have different affinities as well as different selectivities for endothelin-1 and endothelin-3. Furthermore, kidney is the only tissue examined which showed higher binding affinity in the spontaneously hypertensive rats than that of the normotensive ones.


[Redistribution and activation of peritoneal macrophages with the peroral use of sodium nucleinate].
Three hours after the administration of sodium nucleinate the activation of glycolysis, the hexosomonophosphate shunt, the urea cycle (determined by the analysis of key enzymes), the expression of FC gamma-receptors and the decrease of oxidizing phosphorylation were noted in the peritoneal macrophages of mice. By 36 hours the gradual decrease of these characteristics occurred. After three oral administrations of the preparation immature macrophages with lower metabolic activity and increased oxidizing phosphorylation appeared in the exudate, while resident and activated cells practically disappeared. The immaturity of the cells was confirmed by their incubation in vitro. The changes in the cells, revealed in this investigation, are supposed to occur due to the redistribution of activated and intact macrophage populations in situ.


Effectiveness of a 10-day melarsoprol schedule for the treatment of late-stage human African trypanosomiasis: confirmation from a multinational study (IMPAMEL II).
Treatment of late-stage human African trypanosomiasis (HAT) with melarsoprol can be improved by shortening the regimen. A previous trial demonstrated the safety and efficacy of a 10-day treatment schedule. We demonstrate the effectiveness of this schedule in a noncontrolled, multinational drug-utilization study. A total of 2020 patients with late-stage HAT were treated with the 10-day melarsoprol schedule in 16 centers in 7 African countries. We assessed outcome on the basis of major adverse events and the cure rate after treatment and during 2 years of follow-up. The cure rate 24 h after treatment was 93.9%; 2 years later, it was 86.2%. However, 49.3% of patients were lost to follow-up. The overall fatality rate was 5.9%. Of treated patients, 8.7% had an encephalopathic syndrome that was fatal 45.5% of the time. The rate of severe bullous and maculopapular eruptions was 0.8% and 6.8%, respectively. The 10-day treatment schedule was well implemented in the field and was effective. It reduces treatment duration, drug amount, and hospitalization costs per patient, and it increases treatment-center capacity. The shorter protocol has been recommended by the International Scientific Council for Trypanosomiasis Research and Control for the treatment of late-stage HAT caused by Trypanosoma brucei gambiense.


Oxygen Vacancies Boosted Proton Intercalation Kinetics for Aqueous Aluminum-Manganese Batteries.
Aluminum-ion batteries have garnered an extensive amount of attention due to their superior electrochemical performance, low cost, and high safety. To address the limitation of battery performance, exploring new cathode materials and understanding the reaction mechanism for these batteries are of great significance. Among numerous candidates, multiple structures and valence states make manganese-based oxides the best choice for aqueous aluminum-ion batteries (AAIBs). In this work, a new cathode consists of γ-MnO2 with abundant oxygen vacancies. As a result, the electrode shows a high discharge capacity of 481.9 mAh g-1 at 0.2 A g-1 and a sustained reversible capacity of 128.6 mAh g-1 after 200 cycles at 0.4 A g-1. In particular, through density functional theory calculation and experimental comparison, the role of oxygen vacancies in accelerating the reaction kinetics of H+ has been verified. This study provides insights into the application of manganese dioxide materials in aqueous AAIBs.


Pilot study of primary chemotherapy with doxorubicin plus paclitaxel in women with locally advanced or operable breast cancer.
A pilot study of primary chemotherapy with bolus doxorubicin plus paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) infused over 3 hours was performed in 38 women with locally advanced and 41 with stage II/III breast cancer. Patients received four cycles of primary chemotherapy followed by surgery and treatment with cyclophosphamide/methotrexate/5-fluorouracil for six cycles. Preliminary data are available on 73 patients. Doxorubicin plus paclitaxel was well tolerated. Primary toxicity consisted of grade 1 or 2 reversible peripheral neuropathy and grade 3 alopecia. After a median follow-up of 13 months, none of the patients have developed cardiac toxicity or any significant alteration of the left ventricular ejection fraction, which was measured before treatment, at each cycle of doxorubicin plus paclitaxel, and every 3 months thereafter. Major clinical response of the breast tumor was observed in 88% of patients. At pathologic examination of the surgical specimen, 40% were pT1, 15% had no macroscopic tumor residue, and 7% had complete disappearance of invasive neoplastic cells. After a median follow-up of 17 months for patients with locally advanced breast cancer, freedom from progression was 67%, disease-free survival was 71%, and overall survival was 74%. The same end points were 100% for patients with stage II/III disease, with a shorter median follow-up of 10 months. In conclusion, doxorubicin plus paclitaxel is safe, feasible, and effective, and can be used as primary or adjuvant chemotherapy to assess its actual therapeutic role in women with early breast cancer.


Fruitful visual search: inhibition of return in a virtual foraging task.
Inhibition of return (IOR) has long been viewed as a foraging facilitator in visual search. We investigated the contribution of IOR in a task that approximates natural foraging more closely than typical visual search tasks. Participants in a fully immersive virtual reality environment manually searched an array of leaves for a hidden piece of fruit, using a wand to select and examine each leaf location. Search was slower than in typical IOR paradigms, taking seconds instead of a few hundred milliseconds. Participants also made a speeded response when they detected a flashing leaf that either was or was not in a previously searched location. Responses were slower when the flashing leaf was in a previously searched location than when it was in an unvisited location. These results generalize IOR to an approximation of a naturalistic visual search setting and support the hypothesis that IOR can facilitate foraging. The experiment also constitutes the first use of a fully immersive virtual reality display in the study of IOR.


Signaling axis in osteoclast biology and therapeutic targeting in the RANKL/RANK/OPG system.
Bone integrity is maintained through a balance between bone formation and bone resorption, and osteoclasts are primary cells involved in bone resorption. Recent studies have revealed an essential role of macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL) in the development of osteoclasts, and detailed molecular cascades that induce osteoclast differentiation, activation and apoptosis have been clarified. Osteoclasts are involved in various pathologic conditions, such as osteoporosis, rheumatoid arthritis and tumor-induced bone disease, which are characterized by abnormal bone resorption, and the finding of RANKL has provided us a good therapeutic target for such pathologic conditions.


[Method of demonstrating and determining glyphosate in biological matter].
A method was worked out for the extraction of glyphosate from plant and biologic material originating from experimentally treated terrains, animals, and birds. The 'sensitivity' of a number of developers was comparatively studied--used either alone or in combination, choosing the most effective one. It was found that the most proper mobile phase consisted of ethanol : ammonia gas : distilled water in a 1:1:1 ratio and a 0.3 per cent alcohol solution of ninhydrin with a following heating in a kiln at 105 degrees C in the course of 3 to 5 min, with a use of aluminium plaques (Merck production). It is concluded that the method could be employed in all labs as it is highly specific (0.0004 mg glyphosate) and does not require special apparatus.


Effects of hip exercises for chronic low-back pain patients with lumbar instability.
[Purpose] The purpose of this study was to compare hip range of motion between a lumbar stability group and a lumbar instability group, and to evaluate the effectiveness of hip exercises for low-back pain patients with lumbar instability. [Subjects] Seventy-eight patients with chronic low-back pain were the subjects. [Methods] The patients were divided into two groups: a lumbar stability group (n=45) and a lumbar instability group (n=33). They were assessed using the Korean version of the Oswestry Disability Index (KODI) to determine the level of disability of the patients with low-back pain. A 100 mm visual analog scale (VAS) was used to assess low-back pain. [Results] The limitation of hip range of motion of the lumbar instability group was significantly greater than that of the lumbar stability group. Comparisons among four groups at three weeks and six weeks after the start of hip exercises revealed that the VAS score of each group had significantly decreased. Comparisons among four groups at three weeks and at six weeks after the start of hip exercises revealed that the KODI score of each group had significantly decreased. [Conclusion] These findings suggest that the performance of hip exercises by chronic low-back pain patients with lumbar instability is more effective than conventional therapy at reducing low-back pain and levels of disability.


Neoplastic cellularity is associated with clinical and molecular features of high-grade serous ovarian carcinoma.
Most molecular analyses of high-grade serous ovarian, peritoneal and fallopian tube carcinomas (HGSC) require ≥70% tumor (neoplastic) cell nuclei. We characterized the distribution of the percentage of neoplastic nuclei (PNN) in a large cohort of HGSC and correlated PNN with clinical outcomes to determine the fraction of cases outside this range and whether this cut-off introduces selection bias. Subjects were prospectively enrolled and normal and neoplastic tissues were snap-frozen. All subjects had grade 2 to 3 HGSC. Subjects that received neoadjuvant chemotherapy were excluded. PNN was determined by estimating the fraction of neoplastic nuclei relative to non-neoplastic nuclei on a representative hematoxylin and eosin stained frozen section from the primary neoplasm. Germline BRCA mutation status was determined with Sanger or BROCA sequencing. PNN was <70% in 101 (33%) of 306 cases. PNN was significantly higher among subjects without optimal cytoreduction (P=0.018). 55 subjects had germline BRCA1/BRCA2 mutations. HGSC associated with BRCA2 but not BRCA1 mutations had significantly lower PNN compared to HGSC in non-carriers (54% vs. 70%, P=0.018). Overall survival was not significantly different between subjects with <70% or ≥70% PNN (median survival 51.8 vs. 46.6months, P=0.858). One-third of HGSC has PNN <70%. Higher PNN is associated with suboptimal cytoreduction, while lower PNN is associated with inherited BRCA2 mutations. Our findings suggest a nonrandom distribution of PNN that may reflect cancer biology. Further studies exploring the stromal microenvironment are needed. Molecular analyses of HGSC selected for high PNN exclude a significant fraction of patients.


Does the choice of neighbourhood supermarket access measure influence associations with individual-level fruit and vegetable consumption? A case study from Glasgow.
Previous studies have provided mixed evidence with regards to associations between food store access and dietary outcomes. This study examines the most commonly applied measures of locational access to assess whether associations between supermarket access and fruit and vegetable consumption are affected by the choice of access measure and scale. Supermarket location data from Glasgow, UK (n = 119), and fruit and vegetable intake data from the 'Health and Well-Being' Survey (n = 1041) were used to compare various measures of locational access. These exposure variables included proximity estimates (with different points-of-origin used to vary levels of aggregation) and density measures using three approaches (Euclidean and road network buffers and Kernel density estimation) at distances ranging from 0.4 km to 5 km. Further analysis was conducted to assess the impact of using smaller buffer sizes for individuals who did not own a car. Associations between these multiple access measures and fruit and vegetable consumption were estimated using linear regression models. Levels of spatial aggregation did not impact on the proximity estimates. Counts of supermarkets within Euclidean buffers were associated with fruit and vegetable consumption at 1 km, 2 km and 3 km, and for our road network buffers at 2 km, 3 km, and 4 km. Kernel density estimates provided the strongest associations and were significant at a distance of 2 km, 3 km, 4 km and 5 km. Presence of a supermarket within 0.4 km of road network distance from where people lived was positively associated with fruit consumption amongst those without a car (coef. 0.657; s.e. 0.247; p0.008). The associations between locational access to supermarkets and individual-level dietary behaviour are sensitive to the method by which the food environment variable is captured. Care needs to be taken to ensure robust and conceptually appropriate measures of access are used and these should be grounded in a clear a priori reasoning.


Biomarkers in pancreatic adenocarcinoma.
Pancreatic adenocarcinoma is a highly aggressive cancer, with a median patient survival of less than one year. Clinically useful biomarkers capable of accurately assessing prognosis, as well as response to therapy, are urgently needed. At the 2014 ASCO Annual Meeting, Maus et al. (Abstract #e15199) and Neuzillet et al. (Abstract #e15200) present data on use of c-met as a prognostic biomarker, and Shultz et al. (Abstract #4133) use a multiplex antibody panel to identify predictive markers of response to gemcitabine and erlotinib.


Beneficial effects of hyperbaric oxygen therapy on islet transplantation.
We envisage that hyperbaric oxygen (HBO) would ameliorate islet anoxia, preventing early graft failure. Thus, treatment of HBO to diabetic recipients should improve the outcome of islet transplantation. We tested this hypothesis by syngeneically transplanting insufficient number of islets (150 islets) into streptozotocin-diabetic C57BL/6 mice, each followed by HBO (2.4 ATA, 100% O2) therapy for 1.5 h from day 0 to 28, once daily (group A) or twice daily (group B), or from day 5 to 28, once daily (group C) or twice daily (group D), 6 days/week. Recipients without HBO treatment served as controls. At day 28 after transplantation, groups B, C, and D gained weight and had lower blood glucose compared with their baseline values. In addition, groups B and D had higher insulin content of the graft than the controls. To determine the optimal timing of HBO therapy, groups B and D were compared with recipients treated with HBO twice daily, 6 days/week, from day -14 to 0 (group E) and from day -14 to 28 (group F). At day 28 after transplantation, groups B, D, E, and F had significantly lower blood glucose than their individual baseline values and higher insulin content of the graft than controls. But only group F had more beta-cell mass of the graft than controls. These findings lend credence to the expectation that peritransplant application of adequate frequency of HBO to diabetic recipients would enhance the performance and growth of the islet graft, resulting in an improvement of the outcome of the transplantation.


Educational implications for copyright in a digital world.
Statutory law and court cases currently leave fair use of copyrighted material poorly defined and fail to provide effective guidance for the use of others' work. Copyright legislation is undergoing significant change, accelerated by the evolution of computing and communication technologies. This paper reviews copyright issues, fair use guidelines, and applicable laws and statutes to help administrators and educators understand and comply with copyright regulations. The paper describes principles of copyright and ownership, the rights of copyright holders, and the conditions under which copyrighted material can be used by others. Recently introduced legislation, such as the 1998 Digital Millennium Copyright Act, may significantly affect how educators can use copyrighted material in the future. The integration of computer and communication technology into education raises a number of intellectual property issues for dental schools. This paper provides some general guidelines regarding copyright issues in academic environments.


Quantification of Staphylococcus aureus in unpasteurised bovine and caprine milk by real-time PCR.
A sensitive and reproducible real-time PCR assay targeting the nuc gene of Staphylococcus aureus was applied for quantification of this microorganism in artificially and naturally contaminated raw milk samples. The S. aureus cell equivalents (SCEs) estimated by the real-time PCR method were two log scales higher than colony forming units (CFUs) estimated from a plate count method in artificially contaminated milk. The repeatability of the real-time PCR assay including the DNA isolation procedure was assessed by analysing the data derived from naturally contaminated samples. The relative standard deviation of the log-transformed data of four real-time PCR measurements including duplicate DNA isolations ranged between 11.3 and 1.0%. When analysing 80 bovine and 107 caprine naturally contaminated raw milk samples, the real-time PCR method yielded 19.3% more positive samples than the plate count method. With the exception of one sample, SCEs were always higher than CFUs. The difference between SCEs and CFUs was highly variable, and it was not possible to correlate real-time PCR-derived SCEs and CFUs. However, as each SCE detected by real-time PCR indicates a S. aureus cell, which is or has been present in the sample, this method offers the advantage of a retrospective analysis even of processed samples to aid food poisoning-related risk assessment.


Anomalously large capacitance of an ionic liquid described by the restricted primitive model.
We use Monte Carlo simulations to examine the simplest model of a room-temperature ionic liquid (RTIL), called the "restricted primitive model," at a metal surface. We find that at moderately low temperatures the capacitance of the metal-RTIL interface is so large that the effective thickness of the electrostatic double layer is up to three times smaller than the ion radius. To interpret these results we suggest an approach which is based on the interaction between discrete ions and their image charges in the metal surface and which therefore goes beyond the mean-field approximation. When a voltage is applied across the interface, the strong image attraction causes counterions to condense onto the metal surface to form compact ion-image dipoles. These dipoles repel each other to form a correlated liquid. When the surface density of these dipoles is low, the insertion of an additional dipole does not require much energy. This leads to a large capacitance C that decreases monotonically with voltage V, producing a "bell-shaped" curve C(V). We also consider what happens when the electrode is made from a semimetal rather than a perfect metal. In this case, the finite screening radius of the electrode shifts the reflection plane for image charges to the interior of the electrode, and we arrive at a "camel-shaped" C(V). These predictions seem to be in qualitative agreement with experiment.


In vivo modulation of the activity of pyramidal neurons in the rat medial prefrontal cortex by 5-HT2A receptors: relationship to thalamocortical afferents.
The activation of 5-HT(2A) receptors in medial prefrontal cortex (mPFC) by the hallucinogen DOI increases the firing activity of dorsal raphe (DR) 5-HT neurons and prefrontal 5-HT release. Here we show that the i.v. administration of DOI markedly affected the firing rate of identified pyramidal neurons recorded extracellularly. DOI excited (481%) 21/56 neurons, inhibited (11%) 17/56 neurons and left the rest unaffected (overall 2.4-fold increase in firing rate). Both effects were antagonized by 5-HT(2A) receptor blockade. 5-HT(2A)-mediated orthodromic excitations were recorded in pyramidal neurons projecting to DR after electrical stimulation of this nucleus. We also examined whether the effects of DOI in mPFC involve thalamic excitatory inputs. The disinhibition of the mediodorsal and centromedial nuclei of the thalamus by local bicuculline resembled the effects of DOI as it increased pyramidal cell firing and 5-HT release in mPFC. However, the selective activation of prefrontal micro -opioid and mGlu II receptors counteracted the effects of the thalamic disinhibition but not those of DOI. Moreover, extensive thalamic lesions did not alter the effect of DOI on pyramidal cell firing and 5-HT release. We conclude that DOI increases the activity of the mPFC-DR circuit by an action on postsynaptic 5-HT(2A) receptors unrelated to thalamocortical afferents.


Mechanism of action of Vibrio cholerae enterotoxin. Effects on adenylate cyclase of toad and rat erythrocyte plasma membranes.
The characteristics of the cholera toxin-stimulated adenylate cyclase of toad (Bufus marinus) and rat erythrocyte plasma membranes have been examined, with special emphasis on the response to purine nucleotides, fluoride, magnesium and catecholamine hormones. Toad erythrocytes briefly exposed to low concentrations of cholera toxin (40,000 to 60,000 molecules per cell) and incubated 2 to 4 hr at 30 degrees C exhibit dramatic alterations in the kinetic and regulatory properties of adenylate cyclase. The approximate Km for ATP, Mg++ increases from about 1.8 to 3.4 mMin the toxin-stimulated enzyme. The stimulation by cholera toxin increases with increasing ATP, Mg++ concentrations, from 20 percent at low levels (0.2 mM) to 500 percent at high concentrations (greater than 3 mM). Addition of GTP, Mg++ (0.2 mM) restores normal kinetic properties to the toxin-modified enzyme, such that stimulation is most simply explained by an elevation of Vmax. GTP enhances the toxin-treated enzyme activity two- to fourfold at low ATP concentrations, but this effect disappears at high levels of the substrate. At 0.6 mM ATP and 5 mM MgC12 the apparent K alpha for GTP, Mg++ is 5 to 10 muM. The control(unstimulated) enzyme demonstrates a very small response to the guanyl nucleotide, 5'-ITP also stimulates the toxin-treated enzyme but cGMP, guanine, and the pyrimidine nucleotides have no effect. Cholera toxin also alters the activation of adenylate cyclase by free Mg++, decreasing the apparent K alpha from about 25 to 5 mM. (minus)-Epinephrine sensitizes the toad erythrocyte adenylate cyclase to GTP and also decreases the apparent K alpha for free metal. Sodium fluoride, which causes a 70- to 100-fold activation of enzyme activity, has little effect on sensitivity to GTP, and does not change the apparent K alpha for Mg++; moreover,it prevents modulation of these parameters by cholera toxin. Conversely, cholera toxin severely inhibits NaF activation, and in the presence of fluoride ion the usual three to fivefold stimulation by toxin becomes a 30 to 60 percent inhibition of activity. The toxin-stimulated enzyme can be further activated by catecholamines; in the presence of GTP the (minus)-epinephrine stimulation is enhanced by two- to threefold. The increased catecholamine stimulation of toad erythrocyte adenylate cyclase induced by cholera toxin is explained primarily by an increase in the maximal extent of activation by the hormones. Rat erythrocyte adenylate cyclase is also modified by cholera toxin. In the mammalian system the apparent affinity for the hormone appears to be increased. Cholera toxin thus induces profound and nearly permanent changes in adenylate cyclase by a unique process which mimics the stimulation by hormones in important ways, and which also accentuates the normal hormonal response. The relevance of these findings to the mechanism of action of cholera toxin is considered.


Impact of adjuvant chemotherapy on the overall survival of patients with resectable bulky small cell neuroendocrine cervical cancer: a JSGO-JSOG joint study.
The aim of this study was to review the clinicopathological characteristics of small cell neuroendocrine cervical cancer (SCNEC) and to identify the optimal treatment. The Japanese Society of Gynecologic Oncology conducted a retrospective cohort study of SCNECs enrolled in the Gynecological Tumor Registry of the Japan Society of Obstetrics and Gynecology between 2004 and 2015. All cases were modified and unified by International Federation of Gynecology and Obstetrics 2008 (Union for International Cancer Control 7th edition). There were 822 registered patients diagnosed with SCNEC from 2004 to 2015 which comprised 1.1% (822/73,698) of all uterine cervical cancer cases. Rates of lymph-node and distant metastasis were significantly higher in T1b2 (38.9% and 13.7%, respectively) than T1b1 (14.2% and 4.4%, respectively) (p<0.01). In IB2 and T1bN1M0 SCNEC, the 5-year survival rate with surgery followed by chemotherapy was significantly higher than that with surgery followed by radiation therapy/concurrent chemoradiation therapy (p<0.01). SNCEC tumors >4 cm in size had greater rates of lymph-node and distant metastasis when compared with tumors ≤4 cm. Adjuvant chemotherapy, rather than radiotherapy, may improve prognosis after surgery in T1bN1M0 SCNEC.


[Kidney reactivity in helminthiases and after anthelmintic treatment].
The paper provides and analyzes the data available in the literature and the authors' own findings of the structural and functional disturbances in the hosts' kidneys in various helminthiases and following the use of anthelminthic agents. The authors have established the common regularities of renal responses in helminthiases and revealed the specific features of responses to individual groups of anthelminthic agents depending on their dosage and use duration.


[The experience of using magnetic resonance imaging of the uterus and its appendages as an alternative to X-ray hysterosalpingography].
Determination of the diagnostic capabilities of magnetic resonance imaging of the uterus and its appendages (MRHSG) on devices with the induction of the magnetic field 3 Tesla (T) as an alternative to the classic X-ray hysterosalpingography, accompanied by a significant radiation dose to the patient. During the period from April 2015 to February 2016 12 MRHSG was conducted using magnetic resonance imaging apparatus Verio Magnetom 3T, Siemens company (Diagnostic Center "BarsMed", Kazan, Russia). We used neutral and not giving adverse reactions contrast agent – carbon dioxide. The pelvic organs – the uterus and fallopian tubes – represent the zone of interest. Analysis of the data showed that MRHSG on the apparatus with the induction of the magnetic field of 3 T is a highly informative method in the diagnosis of tubal patency, allowing fully assess the state of the pelvic organs on the whole and identify pathology. The absence of radiation exposure and contraindications associated with intolerance to iodinated contrast agents and other side effects differs MRHSG from the traditional X-ray method and makes MRHSG to be an alternative secure method of diagnosis, which has a number of advantages described in the article. MRHSG on the apparatus with the induction of the magnetic field of 3 T in diagnosis of obstruction of the fallopian tubes and the visualization of the uterus and appendages diseases can be optimal and safe alternative to the X-ray hysterosalpingography, which accompanied with radiation exposure and is a number of side effects.


Cervical Lymph Node Metastasis as the Initial Presentation of Femoral Epithelioid Hemangioendothelioma Revealed by 18F-FDG PET/CT.
Femoral epithelioid hemangioendothelioma with cervical lymph node metastasis is rare. We report the FDG PET/CT findings of cervical lymph node metastasis from left femoral epithelioid hemangioendothelioma in a 50-year-old woman with painless enlargement of the left cervical lymph nodes as the initial presentation. Ultrasound and MRI revealed multiple enlarged lymph nodes in the left cervical sheath area. PET/CT showed strong radioactive uptake in the left cervical lymph nodes, and there was additional lesion with increased FDG uptake in the left femur, which was later confirmed as cervical lymph nodes metastasis from left femoral epithelioid hemangioendothelioma by pathological examination.


Lining in nasal reconstruction.
Restoring nasal lining is one of the essential parts during reconstruction of full-thickness defects of the nose. Without a sufficient nasal lining the whole reconstruction will fail. Nasal lining has to sufficiently cover the shaping subsurface framework. But in addition, lining must not compromise or even block nasal ventilation. This article demonstrates different possibilities of lining reconstruction. The use of composite grafts for small rim defects is described. The limits and technical components for application of skin grafts are discussed. Then the advantages and limitations of endonasal, perinasal, and hingeover flaps are demonstrated. Strategies to restore lining with one or two forehead flaps are presented. Finally, the possibilities and technical aspects to reconstruct nasal lining with a forearm flap are demonstrated. Technical details are explained by intraoperative pictures. Clinical cases are shown to illustrate the different approaches and should help to understand the process of decision making. It is concluded that although the lining cannot be seen after reconstruction of the cover it remains one of the key components for nasal reconstruction. When dealing with full-thickness nasal defects, there is no way to avoid learning how to restore nasal lining.


Polymorphisms of Mannose-binding Lectin and Toll-like Receptors 2, 3, 4, 7 and 8 and the Risk of Respiratory Infections and Acute Otitis Media in Children.
Mannose-binding lectin (MBL) and toll-like receptors (TLRs) are important components of the innate immune system. We assessed the susceptibility of children with genetic variants in these factors to respiratory infections, rhinovirus infections and acute otitis media. In a prospective cohort study, blood samples from 381 Finnish children were analyzed for polymorphisms in MBL2 at codons 52, 54 and 57, TLR2 Arg753Gln, TLR3 Leu412Phe, TLR4 Asp299Gly, TLR7 Gln11Leu and TLR8 Leu651Leu. Children were followed up for respiratory infections until 24 months of age with daily diaries. Polymerase chain reaction and antigen tests were used for detection of respiratory viruses from nasal swabs. Children with MBL variant genotype had a mean of 59 days with symptoms of respiratory infection per year, compared with 49 days in those with wild-type (P = 0.01). TLR8 polymorphisms were associated with an increased risk and TLR7 polymorphisms with a decreased risk of recurrent rhinovirus infections (P = 0.02 for both). TLR2 polymorphisms were associated with recurrent acute otitis media (P = 0.02). MBL polymorphisms were associated with an increased and TLR7 polymorphisms with a decreased risk of rhinovirus-associated acute otitis media (P = 0.03 and P = 0.006, respectively). Genetic polymorphisms in MBL and TLRs promote susceptibility to or protection against respiratory infections. In addition to environmental factors, genetic variations may explain why some children are more prone to respiratory infections.


De-implementation strategy to reduce inappropriate use of intravenous and urinary catheters (RICAT): a multicentre, prospective, interrupted time-series and before and after study.
Catheter-associated bloodstream infections and urinary tract infections are frequently encountered health care-associated infections. We aimed to reduce inappropriate use of catheters to reduce health care-associated infections. In this multicentre, interrupted time-series and before and after study, we introduced a de-implementation strategy with multifaceted interventions in seven hospitals in the Netherlands. Adult patients admitted to internal medicine, gastroenterology, geriatic, oncology, or pulmonology wards, and non-surgical acute admission units, and who had a (central or peripheral) venous or urinary catheter were eligible for inclusion. One of the interventions was that nurses in the participating wards attended educational meetings on appropriate catheter use. Data on catheter use were collected every 2 weeks by the primary research physician during the baseline period (7 months) and intervention period (7 months), which were separated by a 5 month transition period. The primary outcomes were percentages of short peripheral intravenous catheters and urinary catheters used inappropriately on the days of data collection. Indications for catheter use were based on international guidelines. This study is registered with Netherlands Trial Register, NL5438. Between Sept 1, 2016, and April 1, 2018, we screened 6157 patients for inclusion, of whom 5696 were enrolled: 2650 patients in the baseline group, and 3046 in the intervention group. Inappropriate use of peripheral intravenous catheters occurred in 366 (22·0%, 95% CI 20·0 to 24·0) of 1665 patients in the baseline group and in 275 (14·4%, 12·8 to 16·0) of 1912 patients in the intervention group (incidence rate ratio [IRR] 0·65, 95% CI 0·56 to 0·77, p<0·0001). Time-series analyses showed an absolute reduction in inappropriate use of peripheral intravenous catheters from baseline to intervention periods of 6·65% (95% CI 2·47 to 10·82, p=0·011). Inappropriate use of urinary catheters occurred in 105 (32·4%, 95% CI 27·3 to 37·8) of 324 patients in the baseline group compared with 96 (24·1%, 20·0 to 28·6) of 398 patients in the intervention group (IRR 0·74, 95% CI 0·56 to 0·98, p=0·013). Time-series analyses showed an absolute reduction in inappropriate use of urinary catheters of 6·34% (95% CI -12·46 to 25·13, p=0·524). Our de-implementation strategy reduced inappropriate use of short peripheral intravenous catheters in patients who were not in the intensive care unit. The reduction of inappropriate use of urinary catheters was substantial, yet not statistically significant in time-series analysis due to a small sample size. The strategy appears well suited for broad-scale implementation to reduce health care-associated infections. Netherlands Organisation for Health Research and Development.


Applying Deep Neural Networks and Ensemble Machine Learning Methods to Forecast Airborne Ambrosia Pollen.
Allergies to airborne pollen are a significant issue affecting millions of Americans. Consequently, accurately predicting the daily concentration of airborne pollen is of significant public benefit in providing timely alerts. This study presents a method for the robust estimation of the concentration of airborne Ambrosia pollen using a suite of machine learning approaches including deep learning and ensemble learners. Each of these machine learning approaches utilize data from the European Centre for Medium-Range Weather Forecasts (ECMWF) atmospheric weather and land surface reanalysis. The machine learning approaches used for developing a suite of empirical models are deep neural networks, extreme gradient boosting, random forests and Bayesian ridge regression methods for developing our predictive model. The training data included twenty-four years of daily pollen concentration measurements together with ECMWF weather and land surface reanalysis data from 1987 to 2011 is used to develop the machine learning predictive models. The last six years of the dataset from 2012 to 2017 is used to independently test the performance of the machine learning models. The correlation coefficients between the estimated and actual pollen abundance for the independent validation datasets for the deep neural networks, random forest, extreme gradient boosting and Bayesian ridge were 0.82, 0.81, 0.81 and 0.75 respectively, showing that machine learning can be used to effectively forecast the concentrations of airborne pollen.


Chemotherapy Delivery Strategies to the Central Nervous System: neither Optional nor Superfluous.
Malignant brain tumors including primary brain tumors (e.g., glioblastoma multiforme) and metastases, are aggressive and lethal entities for the majority of affected patients. Current standard treatments involving combinations of surgery, radiotherapy and systemic chemotherapy offer only modest improvements in survival. Faced with dismal survival, great efforts are deployed to find interesting treatment alternatives. However, the blood-brain barrier (BBB) and the blood-tumor barrier (BTB) remain great obstacles to significant drug delivery to brain tumors. The need to optimize delivery strategies for better patient outcome in the treatment of malignant brain tumors is well acknowledged. Certain interesting strategies use surgical or physical techniques to enhance the distribution of therapeutic agents to the central nervous system. The following strategies will be discussed in this review: intra-arterial delivery, osmotic BBB disruption, intranasal delivery, convection-enhanced delivery and osmotic pumps, implanted polymers, magnetic microspheres and ultrasound BBB disruption. The purpose of this paper is to review the importance of the BBB and the BTB and to review the current status and future perspectives of these delivery procedures.


Traumatic asphyxial deaths due to an uncontrolled crowd.
Nine people died of traumatic asphyxia due to an uncontrolled crowd at a community basketball game in New York City in 1991. We reviewed the circumstances, postmortem findings, and the causes of death. The majority of people had petechiae of the conjunctivae and face consistent with chest compression. There were minimal superficial blunt injuries and no fractures or acute intoxications. These deaths are often incorrectly attributed to blunt force injuries, while the cause typically is asphyxia due to chest compression.


In situ expression of regulatory cytokines by heart inflammatory cells in Chagas' disease patients with heart failure.
Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi. The immune system plays an important role in the reduction of parasite load, but may also contribute to the development of lesions observed during the chronic phase of the disease. We analyzed cytokines produced by inflammatory heart cells in 21 autopsy samples obtained from patients with Chagas' disease divided according to the presence or absence of heart failure (HF). Left ventricular sections were analyzed by immunohistochemistry using antibodies against human IL-4, IFN-γ, TGF-β, TNF-α, and NOS2. In situ mRNA expression was quantified by a Low Density Array. The number of IFN-γ-positive cells was significantly higher than IL-4 positive cells. TNF-α, TGF-β and NOS2 were detected in 65%, 62% and 94% of samples respectively. There was an association between TNF-α-producing cells and the presence of HF. Subjects with HF presented higher levels of STAT4 mRNA, whereas FoxP3 and STAT6 levels were similar in the two groups. A Th1 cytokine pattern predominated in the cardiac inflammatory cell infiltrate of Chagas' disease patients associated with HF. High degree of fibrosis was associated with low NOS2 expression. These results support the idea that Th1 immune responses are involved in heart lesions of Chagas' disease patients.


Effects of dietary salt on angiotensin peptides in kidney.
This study used a novel simple method for the extraction, separation, identification, and quantitation of angiotensin-like immunoactivity from tissue to examine the effects of altering dietary NaCl intake on intrarenal angiotensin I, II, and III levels in salt-sensitive, spontaneously hypertensive rats, salt-resistant Wistar-Kyoto rats, and Sprague-Dawley rats. Seven-week-old male spontaneously hypertensive rats, Wistar-Kyoto rats, and Sprague-Dawley rats were assigned randomly to a diet containing either 8% (high) or 1% (basal) salt and were maintained on these diets for 3 wk. Rats were then decapitated without prior anesthesia, and kidneys were rapidly (< 30 s) removed, snap frozen in liquid nitrogen, and stored at -80 degrees C. Frozen tissue was extracted in 2 M acetic acid and then subjected to solid-phase extraction with the cation exchange resin AG 50W X4. Angiotensin peptides were separated by reversed-phase high-performance liquid chromatography on a phenyl silica gel column with an eluent consisting of 20% acetonitrile in 0.1 M ammonium phosphate buffer, pH 4.9, and quantitated by radioimmunoassay. The elution of standard peptides under isocratic conditions revealed clear resolution of angiotensin I, II, and III and the (1-7) and (3-8) peptides. Recoveries of both labeled and unlabeled angiotensin peptide standards from the extraction step were > 90%. Renal angiotensin II stores were significantly higher in spontaneously hypertensive rats than in Wistar-Kyoto or Sprague-Dawley rats, independent of diet. Renal angiotensin II and III were further suppressed during dietary salt supplementation in both salt-resistant strains but not in the spontaneously hypertensive rat. These findings are consistent with an enhanced (compared with Wistar-Kyoto and Sprague-Dawley rats) role for angiotensin II in the kidney of the salt-sensitive, spontaneously hypertensive rat, particularly under conditions of dietary salt supplementation.


Unidirectional single-frequency operation of a continuous-wave Alexandrite ring laser with wavelength tunability.
High resolution spectroscopy, metrology and quantum technologies (e.g. trapping and cooling) require precision laser sources with narrow linewidth and wavelength tunability. The widespread use of these lasers will be promoted if they are cost-effective, compact and efficient. Alexandrite lasers with a broad tuning band pumped efficiently by low-cost red diodes are a potential candidate, but full performance as a precision light source has not been fully achieved. We present in this work the first continuous-wave (CW) and single-frequency operation of a unidirectional diode-end-pumped Alexandrite ring laser with wavelength tunability. An ultra-compact bow-tie ring cavity is developed with astigmatic compensation and a novel 'displaced mode' design producing CW output power > 1 W in excellent TEM00 mode (M2 < 1.2) when using a low brightness pump (M2 ≥ 30). Wavelength tuning from 727 - 792 nm is demonstrated using a birefringent filter plate. This successful operation opens the prospects of precision light source applications.


Finite element and experimental models of cemented hip joint reconstructions can produce similar bone and cement strains in pre-clinical tests.
Finite element (FE) models could be used for pre-clinical testing of cemented hip replacement implants against the damage accumulation failure scenario. To accurately predict mechanical failure, the models should accurately predict stresses and strains. This should be the case for various implants. In the current study, two FE models of composite hip reconstructions with two different implants were validated relative to experimental bone and cement strains. The objective was an overall agreement within 10% between experimental and FE strains. Two stem types with different clinical results were analyzed: the Lubinus SPII and the Mueller Curved with loosening rates of 4% and 16% after 10 yr, respectively (Prognosis of total hip replacement. 63rd Annual Meeting of the American Academy of orthopaedic surgeons, Atlanta, USA). For both implant types, six stems were implanted in composite femurs. All specimens were subjected to bending. The Mueller Curved specimens were additionally subjected to torsion. Bone strains were recorded at 10 locations on the cortex and cement strains at three locations within the cement mantle. An FE model was built for both stem types and the experiments were simulated. Bone and cement strains were calculated at the experimental gauge locations. Most FE bone strains corresponded to the mean experimental strains within two standard deviations; most FE cement strains within one standard deviation. Linear regression between the FE and mean experimental strains produced slopes between 0.82 and 1.03, and R(2) values above 0.98. Particularly for the Mueller Curved, agreement improved considerably when FE strains were compared to the strains from the experimental specimen used to build the FE model. The objective of overall agreement within 10% was achieved, indicating that both FE models were successfully validated. This prerequisite for accurately predicting long-term failure has been satisfied.


Fractalkine/CX3CR1 signalling in chronic pain and inflammation.
The development of new therapeutic approaches to the treatment of painful neuropathies requires a better understanding of the mechanisms that underlie chronic pain syndromes. There is increasing evidence that immune competent cells such as microglia contribute to the development of chronic pain states. Chemokines play a pivotal role in mediating neuronal-microglial communication which leads to increased nociception. Fractalkine (FKN) is structurally unique amongst the family of chemokines and their receptors and expressed both in the central nervous system and peripheral nerves, as well as in endothelial cells and lymphocytes. Signalling via the CX3CR1 receptor, FKN is able to mediate critical physiological functions necessary for immune regulation. In its soluble forms FKN mediates chemotaxis of immune cells whilst membrane bound FKN acts as an adhesion molecule mediating leukocyte capture and infiltration. As FKN/CX3CR1 is such a key signalling pair for homeostatic functions it is not surprising that it is implicated in a large number of diseases in which imbalance of the immune system is implied. Here we review the evidence that FKN/CX3CR1 mediates neuron-microglial communication in chronic pain states and is therefore key in the development of neuropathic pain. In addition, the contribution of FKN/CX3CR1 signalling to the pathogenesis and progression of two chronic inflammatory conditions, atherosclerosis and rheumatoid arthritis, are discussed.


A profile of destructive surgery in Nepal Eye Hospital.
This is a study profile of the patients undergoing destructive surgery in Nepal Eye Hospital over a period of 2 years (2001-2003). The rationale of the study was to know the incidence and causes for destructive surgery (enucleation/evisceration) and the measures to prevent them. Patients admitted in the ward from emergency and outpatients departments for the purpose of enucleation and evisceration were taken into this study. Their visual acuity, slit-lamp examinations, fundus evaluation were done. Most of the patients had no perception of light with painful blind eyes, panophthalmitis, endophthalmitis, staphylomas, crush injuries and malignancies. After a decision made by the surgeons in the round, a full consent was taken for the operation. Evisceration was done for cases with history of ocular infections and the rest were enucleated. Destructive operation was done for (a) saving the other eye, (b) life saving, (c) painful condition and disfigurement. The incidence of destructive surgery in Nepal Eye Hospital was 1.40%. male : female ratio was 1.41:1. The causes for destructive surgery were panophthalmitis (31.71%), painful blind eye (21.95%), endophthalmitis (14.63%), staphyloma (14.63%), retinoblastoma (12.20%) and crush injuries (4.88%). Number of evisceration (73.17%) was higher than enucleation (26.83%) as most of the cases were sequele of corneal ulcer. Enucleation was mostly seen in children and evisceration in adults. Lastly, the incidences of destructive surgery would be minimized by (a) Prompt treatment of corneal ulcers for reducing panophthalmitis (b) pre, intra, and post operative care in intra ocular surgery for reducing endophthalmitis, and (c) genetic counselling (pre marital) for reducing childhood malignancies. Decision for destructive surgery should be a team work rather than a single surgeon's opinion. It should be done under general anaesthesia or retrobulbar block. Precaution must be taken to prevent the appalling tragedy of enucleating the wrong eye by marking above on the eye to be operated or EUA prior to surgery. Last but not the least, there should be fitting of a prosthesis for cosmesis, psychological support and careful follow-up of the healthy eye.


Pitch Accuracy of Vocal Singing in Deaf Children With Bimodal Hearing and Bilateral Cochlear Implants.
The purpose of the present study was to investigate the pitch accuracy of vocal singing in children with severe to profound hearing loss who use bilateral cochlear implants (CIs) or bimodal devices [CI at one ear and hearing aid (HA) at the other] in comparison to similarly-aged children with normal-hearing (NH). The participants included four groups: (1) 26 children with NH, (2) 13 children with bimodal devices, (3) 31 children with bilateral CIs that were implanted sequentially, and (4) 10 children with bilateral CIs that were implanted simultaneously. All participants were aged between 7 and 11 years old. Each participant was recorded singing a self-chosen song that was familiar to him or her. The fundamental frequencies (F0) of individual sung notes were extracted and normalized to facilitate cross-subject comparisons. Pitch accuracy was quantified using four pitch-based metrics calculated with reference to the target music notes: mean note deviation, contour direction, mean interval deviation, and F0 variance ratio. A one-way ANOVA was used to compare listener-group difference on each pitch metric. A principal component analysis showed that the mean note deviation best accounted for pitch accuracy in vocal singing. A regression analysis examined potential predictors of CI children's singing proficiency using mean note deviation as the dependent variable and demographic and audiological factors as independent variables. The results revealed significantly poorer performance on all four pitch-based metrics in the three groups of children with CIs in comparison to children with NH. No significant differences were found among the three CI groups. Among the children with CIs, variability in the vocal singing proficiency was large. Within the group of 13 bimodal users, the mean note deviation was significantly correlated with their unaided pure-tone average thresholds (r = 0.582, p = 0.037). The regression analysis for all children with CIs, however, revealed no significant demographic or audiological predictor for their vocal singing performance. Vocal singing performance in children with bilateral CIs or bimodal devices is not significantly different from each other on a group level. Compared to children with NH, the pediatric bimodal and bilateral CI users, in general, demonstrated significant deficits in vocal singing ability. Demographic and audiological factors, known from previous studies to be associated with good speech and language development in prelingually-deafened children with CIs, were not associated with singing accuracy for these children.


Measurement of urinary excretion of nonisomerized and beta-isomerized forms of type I collagen breakdown products to monitor the effects of the bisphosphonate zoledronate in Paget's disease.
We have previously shown that the woven pagetic bone in patients with Paget's disease is characterized by an impaired degree of beta-isomerization of C-telopeptides of type I collagen molecules, which results in a preferential urinary excretion of nonisomerized type I collagen C-telopeptide breakdown products (CTX). The aim of this study was to measure the urinary excretion of nonisomerized (alpha) and beta-isomerized (beta) CTX in patients with Paget's disease treated with a bisphosphonate. We studied 28 patients with active Paget's disease of bone who were a part of a randomized, double-blind, placebo-controlled study comparing the effects of several doses of a single injection of zoledronate, a new potent bisphosphonate. Serum bone alkaline phosphatase (BAP) and type I collagen C-terminal extension propeptide (PICP) and urinary excretion of free deoxypyridinoline (free D-Pyr), N-telopeptide breakdown products (NTX), alphaCTX, and betaCTX were measured at baseline and 5, 10, 30, and 60 days after injection. At baseline, all markers were significantly increased in the patients compared with a group of 97 sex- and age-matched controls, with a greater increase in BAP (12-fold), NTX (19-fold), and alphaCTX (10-fold) compared with PICP (2.2-fold), free D-Pyr (2.5-fold), and betaCTX (3-fold). The ratio of alphaCTX to betaCTX was about 3-fold higher than in controls (2.1 versus 0.76; P < 0.001). After a single intravenous injection of zoledronate (200 or 400 microg), all markers decreased within 5 days, except for BAP and free D-Pyr, which decreased on day 10. The maximum decrease was greater and occurred faster for NTX, alphaCTX (-55% after 10 days), and betaCTX (-42% after 10 days) than for free D-Pyr (-25% after 30 days). After the initial decrease, the urinary excretion of betaCTX increased between days 10 and 30 and returned to pretreatment levels after 2 months, in contrast to the sustained decrease in alphaCTX and NTX that was maintained up to 60 days. The urinary ratio of alphaCTX to betaCTX decreased significantly between days 10 and 60, and returned to within the normal range in most patients after 2 months of treatment, probably reflecting the progressive replacement of woven bone by a lamellar bone with a higher and normal degree of beta-isomerization of type I collagen, as previously documented by histology. The determination of the urinary ratio of alphaCTX to betaCTX could be useful for monitoring the effect of bisphosphonate treatment in restoring bone quality in patients with Paget's disease.


Developmental and tissue-specific regulation of hepatocyte nuclear factor 4-alpha (HNF4-alpha) isoforms in rodents.
Hepatocyte nuclear factor 4-alpha (HNF4-alpha) regulates expression of a number of genes in several metabolic organs. The HNF4-alpha gene has two promoters and encodes at least nine isoforms through differential splicing. In mouse liver, transcription initiates at promoter 2 (P2) during fetal life, but switches to P1 at birth. Developmental and tissue-specific expression of HNF4-alpha in other organs is largely unknown. Here, we examined expression of P1- and P2-derived transcripts in a number of mouse and rat tissues. Both P1 and P2 were active in mouse fetal liver, but P2-derived isoforms were detected 50% more abundantly than P1 transcripts. Conversely, the adult mouse liver expressed significantly higher levels of P1- than P2-derived mRNA. In contrast, in the rat, P1 was used more predominantly in both fetal and adult liver. Exposure of fetal rats to the synthetic glucocorticoid dexamethasone caused suppression of P2 while enhancing hepatic expression of transcripts from P1. This was associated with increased expression of erythropoietin and phosphoenolpyruvate carboxykinase, which are key HNF4-alpha targets in the liver. Unlike liver, the kidney and stomach used promoters more selectively, so that only P1-derived isoforms were detected in fetal and adult kidneys in mice or rats, whereas the stomach in both species expressed P2-derived transcripts exclusively. No significant HNF4-alpha mRNA was detected in the spleen. These data reveal striking developmental and tissue-specific variation in expression of HNF4-alpha, and indicate that this can be influenced by environmental factors (such as exposure to glucocorticoid excess), with potential pathophysiological consequences.


Relational discrimination by pigeons in a go/no-go procedure with compound stimuli: a methodological note.
A go/no-go procedure with compound stimuli typically establishes emergent behavior that parallels in structure and typical outcome that of conventional tests for symmetric, transitive, and equivalence relations in normally capable adults. The present study employed a go/no-go compound stimulus procedure with pigeons. During training, pecks to two-component compounds A1B1, A2B2, B1C1, and B2C2 were followed by food. Pecks to compounds A1B2, A2B1, B1C2, and B2C1 re-started the 30-s stimulus presentation interval. The absence of pecking to those compounds for 30 s ended the trial. Subsequent tests presented these components in new spatial arrangements and/or in recombinative compounds that together corresponded to conventional tests of symmetry, transitivity, and equivalence: B1A1, B2A2, C1B1, C2B2, A1C1, A2C2, C1A1, C2A2 vs. B1A2, B2A1, C1B2, C2B1, A1C2, A2C1, C1A2, C2A1 (positive vs. negative instances of symmetric, transitive, and equivalence relations). On tests for symmetric relations, all pigeons behaved in a manner consistent with training on both positive instances (i.e., by responding) and on negative instances (i.e., by not responding). By contrast, the pigeons' behavior on tests for transitivity and equivalence was inconsistent with baseline training, thus failing to show the recombinative discrimination performance that is typical of normally capable humans when trained and tested using the go/no-go procedure with compound stimuli.


[Occurrence of X-linked ichthyosis along with atopy].
The cases of children indicate suffering from X-linked ichthyosis accompanied by atopic diseases (bronchial asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis) which developed in infancy. The examinations revealed microdeletion of the steroid sulfatase region (Xp22.3), increased total IgE value and polysensibilization. It seems that the steroid sulphatase deficiency in ichthyosis played a role in the development of the atopic diseases. The present study suggests the commencement of a strict diet and antihistamine therapy, already in its infancy, in order to prevent the development of the accompanying atopic diseases.


Web-Based Versus Usual Care and Other Formats of Decision Aids to Support Prostate Cancer Screening Decisions: Systematic Review and Meta-Analysis.
Prostate cancer is a leading cause of cancer among men. Because screening for prostate cancer is a controversial issue, many experts in the field have defended the use of shared decision making using validated decision aids, which can be presented in different formats (eg, written, multimedia, Web). Recent studies have concluded that decision aids improve knowledge and reduce decisional conflict. This meta-analysis aimed to investigate the impact of using Web-based decision aids to support men's prostate cancer screening decisions in comparison with usual care and other formats of decision aids. We searched PubMed, CINAHL, PsycINFO, and Cochrane CENTRAL databases up to November 2016. This search identified randomized controlled trials, which assessed Web-based decision aids for men making a prostate cancer screening decision and reported quality of decision-making outcomes. Two reviewers independently screened citations for inclusion criteria, extracted data, and assessed risk of bias. Using a random-effects model, meta-analyses were conducted pooling results using mean differences (MD), standardized mean differences (SMD), and relative risks (RR). Of 2406 unique citations, 7 randomized controlled trials met the inclusion criteria. For risk of bias, selective outcome reporting and participant/personnel blinding were mostly rated as unclear due to inadequate reporting. Based on seven items, two studies had high risk of bias for one item. Compared to usual care, Web-based decision aids increased knowledge (SMD 0.46; 95% CI 0.18-0.75), reduced decisional conflict (MD -7.07%; 95% CI -9.44 to -4.71), and reduced the practitioner control role in the decision-making process (RR 0.50; 95% CI 0.31-0.81). Web-based decision aids compared to printed decision aids yielded no differences in knowledge, decisional conflict, and participation in decision or screening behaviors. Compared to video decision aids, Web-based decision aids showed lower average knowledge scores (SMD -0.50; 95% CI -0.88 to -0.12) and a slight decrease in prostate-specific antigen screening (RR 1.12; 95% CI 1.01-1.25). According to this analysis, Web-based decision aids performed similarly to alternative formats (ie, printed, video) for the assessed decision-quality outcomes. The low cost, readiness, availability, and anonymity of the Web can be an advantage for increasing access to decision aids that support prostate cancer screening decisions among men.


Predominance of Gram-positive bacteria in house dust in the low-allergy risk Russian Karelia.
Simple living conditions and farming environment have been associated with reduced risk for allergic diseases such as atopy and asthma but the factors responsible for this effect remain unresolved. We examined the bacterial composition of house dusts obtained from Finnish and Russian Karelia, two adjacent areas with high and low occurrence of atopic diseases respectively. Two dust mixes, both composed of 10 randomly selected dust samples from 349 Finnish and 417 Russian Karelian households were studied for bacterial biomarkers (DNA, Limulus-active endotoxin, 3-OH fatty acids, muramic acid) and for 16S rRNA gene sequences. Overall, the DNA cloning revealed more taxons (94 different genera) of dustborne bacteria than seen in any previous study on residential environments. Majority (67%) of the bacterial DNA clones in house dust from the low-allergy Russian Kareliarepresented Gram-positive bacteria (Firmicutes and Actinobacteria), predominantly Staphylococcaceae and Corynebacteriaceae. Russian Karelian dust showed up to 20-fold higher contents of muramic acid (marker of Gram-positive bacteria) and a sevenfold higher number of clones of animal-associated species, whereas in Finnish Karelian dust Gram-negatives (mainly Proteobacteria) predominated. Clones of plant-associated bacterial species and of chloroplast, indicating plant biomass, were more numerous in Finnish than in Russian Karelian dust. In conclusion, this study revealed major disparities between Finnish and Russian house dusts. The higher bacterial content and the predominance of Gram-positive bacteria in Russian dust may have implications for occurrence of atopy.


Distribution of an invasive aquatic pathogen (viral hemorrhagic septicemia virus) in the Great Lakes and its relationship to shipping.
Viral hemorrhagic septicemia virus (VHSV) is a rhabdovirus found in fish from oceans of the northern hemisphere and freshwaters of Europe. It has caused extensive losses of cultured and wild fish and has become established in the North American Great Lakes. Large die-offs of wild fish in the Great Lakes due to VHSV have alarmed the public and provoked government attention on the introduction and spread of aquatic animal pathogens in freshwaters. We investigated the relations between VHSV dispersion and shipping and boating activity in the Great Lakes by sampling fish and water at sites that were commercial shipping harbors, recreational boating centers, and open shorelines. Fish and water samples were individually analyzed for VHSV using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and cell culture assays. Of 1,221 fish of 17 species, 55 were VHSV positive with highly varied qRT-PCR titers (1 to 5,950,000 N gene copies). The detections of VHSV in fish and water samples were closely associated and the virus was detected in 21 of 30 sites sampled. The occurrence of VHSV was not related to type of site or shipping related invasion hotspots. Our results indicate that VHSV is widely dispersed in the Great Lakes and is both an enzootic and epizootic pathogen. We demonstrate that pathogen distribution information could be developed quickly and is clearly needed for aquatic ecosystem conservation, management of affected populations, and informed regulation of the worldwide trade of aquatic organisms.


Correlation of bronchoalveolar lavage and clinical and functional findings in asbestosis.
Respiratory clinical, radiographic, and functional findings were assessed and correlated with bronchoalveolar lavage (BAL) cellular changes in 52 asbestos workers (27 with and 25 without asbestosis) and in 15 control subjects without asbestos exposure. Subjects with asbestosis had a moderate neutrophilic alveolitis (7.8 +/- 5%) compared with the other groups (p less than 0.001) that was correlated with the presence of crackles (p = 0.03) and PaO2 (p less than 0.05) and AaPO2 at rest (p less than 0.05) values. Asbestos bodies (AB) in BAL were quantitated in 34 of the 52 asbestos workers (21 with and 13 without asbestosis) and in the control group. They were present in 83% of asbestos workers but they were absent in the latter. No significant differences were observed in the number of AB between those asbestos workers with and without lung disease. We conclude that crackles on auscultation and PaO2 and AaPO2 values may well be good indicators of the staging of neutrophilic alveolitis in asbestosis. In contrast, the amount of AB in BAL is not a reliable marker of asbestos lung fibrosis.


Family intervention for schizophrenia.
People with schizophrenia from families that express high levels of criticism, hostility, or over involvement, have more frequent relapses than people with similar problems from families that tend to be less expressive of emotions. Forms of psychosocial intervention, designed to reduce these levels of expressed emotions within families, are now widely used. To estimate the effects of family psychosocial interventions in community settings for people with schizophrenia or schizophrenia-like conditions compared with standard care. We updated previous searches by searching the Cochrane Schizophrenia Group Trials Register (September 2008). We selected randomised or quasi-randomised studies focusing primarily on families of people with schizophrenia or schizoaffective disorder that compared community-orientated family-based psychosocial intervention with standard care. We independently extracted data and calculated fixed-effect relative risk (RR), the 95% confidence intervals (CI) for binary data, and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated mean differences (MD). This 2009-10 update adds 21 additional studies, with a total of 53 randomised controlled trials included. Family intervention may decrease the frequency of relapse (n = 2981, 32 RCTs, RR 0.55 CI 0.5 to 0.6, NNT 7 CI 6 to 8), although some small but negative studies might not have been identified by the search. Family intervention may also reduce hospital admission (n = 481, 8 RCTs, RR 0.78 CI 0.6 to 1.0, NNT 8 CI 6 to 13) and encourage compliance with medication (n = 695, 10 RCTs, RR 0.60 CI 0.5 to 0.7, NNT 6 CI 5 to 9) but it does not obviously affect the tendency of individuals/families to leave care (n = 733, 10 RCTs, RR 0.74 CI 0.5 to 1.0). Family intervention also seems to improve general social impairment and the levels of expressed emotion within the family. We did not find data to suggest that family intervention either prevents or promotes suicide. Family intervention may reduce the number of relapse events and hospitalisations and would therefore be of interest to people with schizophrenia, clinicians and policy makers. However, the treatment effects of these trials may be overestimated due to the poor methodological quality. Further data from trials that describe the methods of randomisation, test the blindness of the study evaluators, and implement the CONSORT guidelines would enable greater confidence in these findings.


Hepatitis C Virus Genotype and Subtype Distribution in Patient Specimens Tested at the University of Texas Medical Branch, Galveston, Between January 2011 and November 2014.
Hepatitis C virus (HCV) genotype/subtype data are routinely generated in clinical laboratories to guide treatment. Genotype data can also inform genotype distribution and molecular epidemiology of HCV infections in patient populations and geographical regions that clinics/laboratories serve. The aim of this study was to determine the distribution of HCV genotypes/subtypes and their association with demographic characteristics among the patients that were routinely tested in the Molecular Diagnostics Laboratory at The University of Texas Medical Branch (UTMB) at Galveston. Among the 6573 patients tested between January 2011 and November 2014, the most frequent HCV genotype/subtype was 1a (65.3%), followed by 3a (11.5%), 1b (10.4%), and 2b (8.8%). Combined, genotype 4 and genotype 6 were found in less than 1% of this cohort. Approximately 1.3% of the patients presented multiple genotypes/subtypes. Factors independently associated with genotypes and subtypes were race/ethnicity, sex, and patient age.


Signal detection and noise suppression using a wavelet transform signal processor: application to ultrasonic flaw detection.
The utilization of signal processing techniques in nondestructive testing, especially in ultrasonics, is widespread. Signal averaging, matched filtering, frequency spectrum analysis, neural nets, and autoregressive analysis have all been used to analyze ultrasonic signals. The Wavelet Transform (WT) is the most recent technique for processing signals with time-varying spectra. Interest in wavelets and their potential applications has resulted in an explosion of papers; some have called the wavelets the most significant mathematical event of the past decade. In this work, the Wavelet Transform is utilized to improve ultrasonic flaw detection in noisy signals as an alternative to the Split-Spectrum Processing (SSP) technique. In SSP, the frequency spectrum of the signal is split using overlapping Gaussian passband filters with different central frequencies and fixed absolute bandwidth. A similar approach is utilized in the WT, but in this case the relative bandwidth is constant, resulting in a filter bank with a self-adjusting window structure that can display the temporal variation of the signal's spectral components with varying resolutions. This property of the WT is extremely useful for detecting flaw echoes embedded in background noise. The detection of ultrasonic pulses using the wavelet transform is described and numerical results show good detection even for signal-to-noise ratios (SNR) of -15 dB. The improvement in detection was experimentally verified using steel samples with simulated flaws.


Parallel 2-d convolution on a mesh connected array processor.
In this correspondence, a parallel 2-D convolution scheme is presented. The processing structure is a mesh connected array processor consisting of the same number of simple processing elements as the number of pixels in the image. For most windows considered, the number of computation steps required is the same as that of the coefficients of a convolution window. The proposed scheme can be easily extended to convolution windows of arbitrary size and shape. The basic idea of the proposed scheme is to apply the 1-D systolic concept to 2-D convolution on a mesh structure. The computation is carried out along a path called a convolution path in a systolic manner. The efficiency of the scheme is analyzed for windows of various shapes. The ideal convolution path is a Hamiltonian path ending at the center of the window, the length of which is equal to the number of window coefficients. The simple architecture and control strategy make the proposed scheme suitable for VLSI implementation.


Crossover-active regions of the wheat genome are distinguished by DMC1, the chromosome axis, H3K27me3, and signatures of adaptation.
The hexaploid bread wheat genome comprises over 16 gigabases of sequence across 21 chromosomes. Meiotic crossovers are highly polarized along the chromosomes, with elevation in the gene-dense distal regions and suppression in the Gypsy retrotransposon-dense centromere-proximal regions. We profiled the genomic landscapes of the meiotic recombinase DMC1 and the chromosome axis protein ASY1 in wheat and investigated their relationships with crossovers, chromatin state, and genetic diversity. DMC1 and ASY1 chromatin immunoprecipitation followed by sequencing (ChIP-seq) revealed strong co-enrichment in the distal, crossover-active regions of the wheat chromosomes. Distal ChIP-seq enrichment is consistent with spatiotemporally biased cytological immunolocalization of DMC1 and ASY1 close to the telomeres during meiotic prophase I. DMC1 and ASY1 ChIP-seq peaks show significant overlap with genes and transposable elements in the Mariner and Mutator superfamilies. However, DMC1 and ASY1 ChIP-seq peaks were detected along the length of each chromosome, including in low-crossover regions. At the fine scale, crossover elevation at DMC1 and ASY1 peaks and genes correlates with enrichment of the Polycomb histone modification H3K27me3. This indicates a role for facultative heterochromatin, coincident with high DMC1 and ASY1, in promoting crossovers in wheat and is reflected in distalized H3K27me3 enrichment observed via ChIP-seq and immunocytology. Genes with elevated crossover rates and high DMC1 and ASY1 ChIP-seq signals are overrepresented for defense-response and immunity annotations, have higher sequence polymorphism, and exhibit signatures of selection. Our findings are consistent with meiotic recombination promoting genetic diversity, shaping host-pathogen co-evolution, and accelerating adaptation by increasing the efficiency of selection.


Pollinator communities in strawberry crops - variation at multiple spatial scales.
Predicting potential pollination services of wild bees in crops requires knowledge of their spatial distribution within fields. Field margins can serve as nesting and foraging habitats for wild bees and can be a source of pollinators. Regional differences in pollinator community composition may affect this spill-over of bees. We studied how regional and local differences affect the spatial distribution of wild bee species richness, activity-density and body size in crop fields. We sampled bees both from the field centre and at two different types of semi-natural field margins, grass strips and hedges, in 12 strawberry fields. The fields were distributed over four regions in Northern Europe, representing an almost 1100 km long north-south gradient. Even over this gradient, daytime temperatures during sampling did not differ significantly between regions and did therefore probably not impact bee activity. Bee species richness was higher in field margins compared with field centres independent of field size. However, there was no difference between centre and margin in body-size or activity-density. In contrast, bee activity-density increased towards the southern regions, whereas the mean body size increased towards the north. In conclusion, our study revealed a general pattern across European regions of bee diversity, but not activity-density, declining towards the field interior which suggests that the benefits of functional diversity of pollinators may be difficult to achieve through spill-over effects from margins to crop. We also identified dissimilar regional patterns in bee diversity and activity-density, which should be taken into account in conservation management.


Human pluripotent stem cell-derived alveolar organoids: Cellular heterogeneity and maturity.
Chronic respiratory diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and respiratory infections injure the alveoli; the damage evoked is mostly irreversible and occasionally leads to death. Achieving a detailed understanding of the pathogenesis of these fatal respiratory diseases has been hampered by limited access to human alveolar tissue and the differences between mice and humans. Thus, the development of human alveolar organoid (AO) models that mimic in vivo physiology and pathophysiology has gained tremendous attention over the last decade. In recent years, human pluripotent stem cells (hPSCs) have been successfully employed to generate several types of organoids representing different respiratory compartments, including alveolar regions. However, despite continued advances in three-dimensional (3D) culture techniques and single-cell genomics, there is still a profound need to improve the cellular heterogeneity and maturity of AOs to recapitulate the key histological and functional features of in vivo alveolar tissue. In particular, the incorporation of immune cells such as macrophages into hPSC-AO systems is crucial for disease modeling and subsequent drug screening. In this review, we summarize current methods for differentiating alveolar epithelial cells from hPSCs followed by AO generation and their applications in disease modeling, drug testing, and toxicity evaluation. In addition, we review how current hPSC-AOs closely resemble in vivo alveoli in terms of phenotype, cellular heterogeneity, and maturity.


Transstadial transmission of Francisella tularensis holarctica in mosquitoes, Sweden.
In Sweden, human cases of tularemia caused by Francisella tularensis holarctica are assumed to be transmitted by mosquitoes, but how mosquito vectors acquire and transmit the bacterium is not clear. To determine how transmission of this bacterium occurs, mosquito larvae were collected in an area where tularemia is endemic, brought to the laboratory, and reared to adults in their original pond water. Screening of adult mosquitoes by real-time PCR demonstrated F. tularensis lpnA sequences in 14 of the 48 mosquito pools tested; lpnA sequences were demonstrated in 6 of 9 identified mosquito species. Further analysis confirmed the presence of F. tularensis holarctica-specific 30-bp deletion region sequences (FtM19inDel) in water from breeding containers and in 3 mosquito species (Aedes sticticus, Ae. vexans, and Ae. punctor) known to take blood from humans. Our results suggest that the mosquitoes that transmit F. tularensis holarctica during tularemia outbreaks acquire the bacterium already as larvae.


(In)appropriate neurosurgical consultation.
Whether or not a patient could benefit from a computed tomography (CT) scan and/or the evaluation by a neurosurgeon requires judgment by a clinician of the risk of clinical deterioration. To assess this clinical process we aimed to determine how many of the consultations to the Neurosurgical department (NSG) of UC Davis are appropriately indicated for neurosurgical input or management. Secondly, we investigated how CT is used in the University of California Davis Medical Center (UCDMC) in NSG consults of head injured patients compared to a validated and highly sensitive decision making tool, the Canadian CT Head Rule (CCHR). Patients were enrolled in this prospective study if they presented to a department of UCDMC other than neurosurgery and when, consequently, the NSG was consulted. The emergency consultations were categorized into three groups: head injury, spine injury and others. Subsequently, the appropriateness of the consultations was evaluated based on the need for evaluation determined by the likelihood of clinically important intracranial lesions for head injury and by the likelihood of clinically important spinal cord injury or spinal cord instability for spine injury. Of the head injured patients with a CT scan the appropriateness of the scan was determined by way of the CCHR. Between 21 July and 15 August 2008 99 consultations were included: 32 patients with head injuries, 29 with spine injuries, 34 with other diseases and 4 not sufficiently documented patients. 23 classified inappropriate, 69 appropriate and 7 remained unclassified. Of the head injured patients, 10 (31.2%) had gotten a CT scan that was classified inappropriate. NSG receives 3-4 requests for consultations per day from the other services of UCDMC, of which one is of questionable validity and one of the three CT scans for head injury is not necessary. These results suggest the use of the CCHR in UCDMC would improve patient care and could result in large health-care savings, while there would also be less radiation exposure.


[Changes in cranial size and configuration in infants].
Abnormalities of cranial size and configuration include macrocephaly, microcephaly and dysmorphic skull. Hydrocephalus, mega-encephalus, abnormal growth of skull bones and chronic subdural and epidural collections are among the most important causes of macrocephaly. Primary microcephaly may be due to deficient neuronal proliferation or abnormalities in neural tube segmentation or cellular migration. Secondary microcephaly may be caused by prenatal, perinatal or early postnatal insults like infections, drugs, radiation, hypoxia, among others. Abnormal cranial forms may be sporadic or secondary to genetic and chromosomal diseases. Craniosynostosis can be managed surgically with positive results when early diagnosis and treatment are accomplished.