Subepicardial delayed gadolinium enhancement in asymptomatic athletes: let sleeping dogs lie?
Subepicardial delayed gadolinium enhancement (DGE) patches without underlying cardiomyopathy is poorly understood. It is often reported as the result of prior silent myocarditis. Its prognostic relevance in asymptomatic athletes is unknown; therefore, medical clearance for competitive sports participation is debated. This case series aims to relate this pattern of DGE in athletes to outcome. We report on seven young asymptomatic athletes with isolated subepicardial DGE detected during workup of abnormalities on their regular screening examination, that is, pathological T-wave inversions on ECG (n=4) or ventricular arrhythmias on exercise test (n=3). All underwent a comprehensive initial investigation in order to assess left ventricular (LV) function at rest and exercise (exercise cardiac MRI and/or exercise echocardiography) and occurrence of arrhythmias (exercise test, 24 h-ECG Holter, electrophysiological study). All underwent a careful follow-up with biannual evaluation. All athletes had extensive subepicardial DGE (12.0±4.8% of LV mass), predominantly in the lateral wall. Three athletes had non-sustained ventricular arrhythmias, whereas two of them had LV ejection fraction <50% at rest with no contractile reserve at exercise. During a follow-up of 3.0±1.5 years in the four remaining athletes, two had symptomatic ventricular tachycardia and one demonstrated progressive LV dysfunction. Hence, six of seven athletes had to be excluded from competitive sports participation. Isolated large areas of subepicardial DGE in an asymptomatic athlete are not benign and require a careful evaluation at exercise and a strict follow-up. These findings question whether extreme exercise during silent myocarditis may facilitate fibrosis generation and adverse remodelling.


Hydrogen Production During Ethylene Glycol Photoreactions Over Ag-Pd/TiO2 at Different Partial Pressures of Oxygen.
The reaction of ethylene glycol has been studied over Ag-Pd/TiO2 (anatase) under photo-irradiation while monitoring the reaction products (in the gas and liquid phases) as a function of time and at different partial pressures of molecular oxygen. The catalyst contained metal particles with a mean size of about 1 nm, most likely in the form of alloy (TEM, STEM, and XPS). The complex reaction network involves hydrogen abstraction, C-C bond dissociation, de-carbonylation and water gas shift ultimately yielding hydrogen and CO2. The two main competing reactions were found to be, photo reforming and photo-oxidation. Based on our previous study, Ag presence improves the reaction rate for hydrogen production, most likely via decreasing the adsorption energy of CO when compared to pure Pd. At high ethylene glycol concentrations, the rate of hydrogen produced decreased by a factor of two while changing O2 partial pressure from 0.001 to 0.2 atm. The rate was however very sensitive to oxygen partial pressures at low ethylene glycol concentrations, decreasing by about 50 times with increasing oxygen pressures to 1 atm. The order of reaction with respect to O2 changed from near zero at high oxygen partial pressure to ½ at low partial pressure (in 0.008-0.2 atm. range). Liquid phase analysis indicated that the main reaction product was formaldehyde, where its concentration was found to be higher than that of H2 and CO2. The mass balance approached near unity only upon the incorporation of formaldehyde and after a prolonged reaction time. This suggests that the photo-reforming reaction was not complete even at prolonged time, most likely due to kinetic limitations.


Host-associated genetic import in Campylobacter jejuni.
Host association of Campylobacter jejuni was analyzed by using multilocus sequence typing data for 713 isolates from chickens and bovids (cattle and sheep). Commonly used summary measures of genotypes (sequence type and clonal complex) showed poor accuracy, but a method using the full allelic profile showed 80% accuracy in distinguishing isolates from these 2 host groups. We explored the biologic basis of more accurate results with allelic profiles. Strains isolated from specific hosts have imported a substantial number of alleles while circulating in those host species. These results imply that 1) although Campylobacter moves frequently between hosts, most transmission is within species, and 2) lineages can acquire a host signature and potentially adapt to the host through recombination. Assignment using this signature enables improved prediction of source for pathogens that undergo frequent genetic recombination.


Spinal solitary fibrous tumors: a series of four patients: case report.
Intraspinal solitary fibrous tumors, which are rare mesenchymal tumors, have previously been reported as case reports. We review our experience and, to our knowledge, the first small institutional series with respect to clinical presentation, diagnosis, surgical management, pathohistological analysis, progression-free survival, and long-term outcome. In this retrospective review, four patients (three male and one female) ranging in age from 17 to 59 years (mean, 38.5 yr) had spinal solitary fibromas located throughout the spinal canal. Three tumors were located in the thoracic region and one in the cervical spine. All patients presented with pain and paresthesia. Two patients had an associated spinal deformity. All had gross total resection as confirmed by postoperative imaging studies. All four patients underwent surgical treatment for spinal solitary fibromas. None of these patients underwent irradiation or chemotherapy after surgery at our center; therefore, outcome was attributed to surgery alone. There were no surgical deaths, and the 5-year actuarial survival rate was 100%. At the most recent follow-up examination, neurological function was stable or improved in 90% of patients. Patients with solitary fibrous tumors have a long survival. These tumors have an indolent course, and radiotherapy or chemotherapy seems to be unnecessary.


Optimization of the Sistrom Culture Medium for Large-Scale Batch Cultivation of Rhodospirillum rubrum under Semiaerobic Conditions with Maximal Yield of Photosynthetic Membranes.
The defined medium A of W. R. Sistrom (W. R. Sistrom, J. Gen. Microbiol. 22:77-85, 1960) has been modified to allow the growth of Rhodospirillum rubrum in large-scale batch cultures under dark, semiaerobic conditions. The simultaneous use of two substrates, NH(4)-succinate (46 mM) and fructose (0.3%), which are utilized in aerobic and fermentative metabolism, respectively, leads to very high cell densities with a maximal yield of photosynthetic membranes.


Vagal nerve stimulator: a new approach to medically refractory epilepsy.
Repetitive vagal nerve stimulation (VNS) is a new, FDA-approved treatment for medically refractory epilepsy. The device is implanted subcutaneously in the left chest and sends intermittent impulses to the left vagus nerve through communicating leads. Twelve patients have been implanted to date. The ages of the patients range from 8 to 36 years and the average followup at this point is five months. Five patients have achieved a greater than 50 percent reduction in seizure frequency with no serious adverse effects.


Impact of image reconstruction parameters when using 3D DSA reconstructions to measure intracranial aneurysms.
Safe and effective use of newly developed devices for aneurysm treatment requires the ability to make accurate measurements in the angiographic suite. Our purpose was to determine the parameters that optimize the geometric accuracy of three-dimensional (3D) vascular reconstructions. An in vitro flow model consisting of a peristaltic pump, plastic tubing, and 3D printed patient-specific aneurysm models was used to simulate blood flow in an intracranial aneurysm. Flow rates were adjusted to match values reported in the literature for the internal carotid artery. 3D digital subtraction angiography acquisitions were obtained using a commercially available biplane angiographic system. Reconstructions were done using Edge Enhancement (EE) or Hounsfield Unit (HU) kernels and a Normal or Smooth image characteristic. Reconstructed images were analyzed using the vendor's aneurysm analysis tool. Ground truth measurements were derived from metrological scans of the models with a microCT. Aneurysm volume, surface area, dome height, minimum and maximum ostium diameter were determined for the five models. In all cases, measurements made with the EE kernel most closely matched ground truth values. Differences in values derived from reconstructions displayed with Smooth or Normal image characteristics were small and had only little impact on the geometric parameters considered. Reconstruction parameters impact the accuracy of measurements made using the aneurysm analysis tool of a commercially available angiographic system. Absolute differences between measurements made using reconstruction parameters determined as optimal in this study were, overall, very small. The significance of these differences, if any, will depend on the details of each individual case.


Oxycodone involvement in drug abuse deaths. II. Evidence for toxic multiple drug-drug interactions.
Recent surveys suggest that the abuse of drugs, often in combination, is pervasive throughout society. Adverse consequences of drug abuse tend to be attributed to the single drug "most likely" to be responsible. This is frequently seen in fatality cases, particularly those involving opioids. However, it is difficult to determine the specific cause of death when multiple drugs are involved. Although enhanced toxicity of alcohol and other centrally acting drugs with opioids has been well established in animal studies, there is a paucity of data in well-controlled human studies. We evaluated 1014 fatality cases involving oxycodone (OXC) for evidence of enhanced toxicity associated with multiple drug-drug interactions. We previously reported on these cases, and we classified them by a standardized method into groups that distinguished cases unrelated to drug abuse from those related to drug abuse, cases that involved only OXC from cases involving multiple drugs, drug-induced fatalities from drug-related fatalities, and cases in which the specific drug product OxyContin (oxycodone HCl controlled-release) tablets were identified from cases where OxyContin was not identified. Our working hypothesis was that OXC in combination with other centrally acting drugs is more toxic than OXC alone, evidenced by the finding of lower mean blood concentrations of OXC in multiple drug-induced deaths compared to single (OXC only) drug-induced deaths. Assessment of blood levels determined by specific assay methodology (primarily gas chromatography-mass spectrometry) in these cases provided the following mean postmortem concentrations of OXC: multiple drug-induced deaths, OxyContin identified, 0.93 mg/mL (N = 167); multiple drug-induced deaths, OxyContin not identified, 0.73 mg/mL (N = 579); single (OXC) drug-induced deaths, OxyContin identified, 1.55 mg/mL (N = 12); and single (OXC) drug-induced deaths, OxyContin not identified, 1.70 mg/mL (N = 15). Overall, mean OXC concentration trends were as follows: single (OXC), drug-induced, drug abuse deaths > multiple, drug-induced drug abuse deaths > drug-related drug abuse deaths approximately deaths unrelated to drug abuse; and deaths in which OxyContin was identified approximately deaths in which OxyContin was not identified, whether the deaths involved oxycodone alone or multiple drugs. Drug abuse patterns in the multiple drug-induced cases were complex. Over 135 drugs that were considered to be plausibly contributory to enhanced toxicity were identified in body fluids and tissues. Evaluation of mean OXC blood concentrations in cases that contained one, two, three, four, five, and six or more contributory drugs in combination demonstrated consistently lower mean OXC concentrations than those cases in which OXC was the only drug identified. A smaller number of cases were evaluated in the multiple drug-induced groups in which OXC was paired with a single other contributory drug. The overall mean OXC concentration for these cases was 0.71 mg/mL (N = 90) as compared to 1.64 mg/mL (N = 27) for the cases in the single drug-induced groups. The consistent finding of lower mean OXC blood levels associated with multiple drug-induced fatalities supports the stated hypothesis that OXC in combination with other centrally active drugs is more toxic than when OXC was the only drug involved. It was concluded that in cases of multiple drug fatalities, cause of death (COD) should not be attributed to any single drug. Rather, the unique combination of drugs, the pattern of drug use/abuse, and individual factors, such as tolerance to the respiratory depressant effects of opioids, must be taken into account in arriving at a valid COD statement.


Demographic and clinical characteristics of type 1 diabetes mellitus in omani children - single center experience.
To describe the demographic characteristics and clinical presentation of Omani children with type 1 diabetes mellitus at Sultan Qaboos University Hospital, Muscat, Oman. A retrospective analysis of all children with type 1 diabetes mellitus attending the Pediatric Endocrine Unit at Sultan Qaboos University Hospital, Oman from June 2006 to May 2013. One hundred and forty-four patients were included in the study. The mean±SD of age at diagnosis was 6.7 ± 3.7 years. The median duration of symptoms was 10 days (IQR; 5-14). The most commonly reported presenting symptoms were polyuria (94%), polydipsia (82%), and weight loss (59%). Diabetic ketoacidosis at initial presentation was diagnosed in 31% of the patients. Different insulin regimens were prescribed: multiple daily injections in 109 (76%) patients, twice daily insulin regimen in 23 (16%) patients, and insulin pump therapy in 12 (8%) patients. Family history of type 1 diabetes mellitus was present in 31 (22%) patients. There were no significant differences in presenting complaints (polyuria, p=0.182; polydipsia, p=0.848), duration of symptoms (p=0.331), reported weight loss (p=0.753), or diabetic ketoacidosis at presentation (p=0.608) between patients with and without family history of type 1 diabetes mellitus. Polyuria, polydipsia and weight loss are the most common presenting symptoms. Family history of type 1 diabetes mellitus is highly prevalent among the studied patients. Diabetic ketoacidosis was found to be less common in Oman compared to other diabetes centers in the Middle East.


Near-field signature of electromagnetic coupling in metamaterial arrays: a terahertz microscopy study.
Using terahertz near-field imaging we experimentally investigate the interaction between split-ring resonators (SRRs) in metamaterial arrays. Depending on the inter-SRR spacing two regimes can be distinguished for which strong coupling between SRRs occurs. For dense arrays SRRs couple via their electric and magnetic near-fields. In this case distinct deformations of the SRRs' characteristic near-field patterns are observed as a signature of their strong interaction. For larger separations with a periodicity matching the resonance wavelength, the SRRs become diffractively coupled via their radiated fields. In this regime hybridization between plasmonic and lattice modes can be clearly identified in the experimentally obtained near-field maps.


Blood chemical abnormalities in cattle with ruptured bladders and ruptured urethras.
A study was undertaken to determine the blood chemical variables and compare changes that occurred with ruptured bladders and ruptured urethras in steers and yearling bulls. The fatality rates were 10.5% in steers with ruptured urethras and 50.8% in steers with ruptured bladders. Both groups had significantly decreased serum sodium and chloride values and significantly increased serum creatinine, blood urea nitrogen, and plasma protein concentrations compared to the normal group. Steers with ruptured bladders were more dehydrated, had significantly lower serum sodium and chloride values and had significantly higher blood urea nitrogen concentrations than steers with ruptured urethras. The combination of a decreased serum sodium, a decreased serum chloride, and a decreased ratio of serum phosphate to blood urea nitrogen occurred consistently within the ruptured bladder group. Of the variables examined, serum phosphate was the best prognostic indicator in the steers with ruptured bladders as all of the steers that died had a serum phosphate in excess of 2.9 mmol/L. The fluid and electrolyte changes are discussed.


Label-free luminescence switch-on detection of T4 polynucleotide kinase activity using a G-quadruplex-selective probe.
A label-free, oligonucleotide-based, switch-on luminescence detection method for T4 polynucleotide kinase activity has been developed using a novel G-quadruplex-selective luminescent Ir(iii) complex probe. The application of the assay for screening potential T4 PNK inhibitors is also demonstrated. To our knowledge, this is the first metal-based assay for PNK activity.


Morphological and physiological retinal degeneration induced by intravenous delivery of vitamin A dimers in rabbits.
The eye uses vitamin A as a cofactor to sense light and, during this process, some vitamin A molecules dimerize, forming vitamin A dimers. A striking chemical signature of retinas undergoing degeneration in major eye diseases such as age-related macular degeneration (AMD) and Stargardt disease is the accumulation of these dimers in the retinal pigment epithelium (RPE) and Bruch's membrane (BM). However, it is not known whether dimers of vitamin A are secondary symptoms or primary insults that drive degeneration. Here, we present a chromatography-free method to prepare gram quantities of the vitamin A dimer, A2E, and show that intravenous administration of A2E to the rabbit results in retinal degeneration. A2E-damaged photoreceptors and RPE cells triggered inflammation, induced remolding of the choroidal vasculature and triggered a decline in the retina's response to light. Data suggest that vitamin A dimers are not bystanders, but can be primary drivers of retinal degeneration. Thus, preventing dimer formation could be a preemptive strategy to address serious forms of blindness.


Glucose-6-phosphate dehydrogenase deficiency in retinal vein occlusion.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common human genetic abnormalities, with a high prevalence in Sardinia, Italy. Evidence indicates that G6PD-deficient patients are protected against ischemic heart and cerebrovascular disease. The purpose of this study was to assess the frequency of G6PD deficiency in Sardinian patients with retinal vein occlusion (RVO) and to ascertain whether the deficiency may offer protection against RVO. Erythrocyte G6PD levels were measured in 448 consecutive RVO patients: 194 with central RVO (CRVO) and 254 with branch RVO (BRVO). Age- and sex-matched subjects (n = 896) who were undergoing cataract surgery and had no history of RVO served as the control. Multiple logistic regression models were used to investigate the association between G6PD deficiency and RVO, CRVO, or BRVO. G6PD deficiency was found in 21 (4.7%) patients with RVO, 7 (3.6%) with CRVO, 14 (5.5%) with BRVO, and 107 (11.9%) control subjects. Differences between cases and controls were statistically significant (P < 0.005). Multiple conditional logistic regression analysis, including as covariates G6PD deficiency, hypertension, diabetes, and hypercholesterolemia, revealed that G6PD deficiency was significantly associated with decreased risk of development of RVO, CRVO, or BRVO. After adjustment for hypertension, diabetes, and hypercholesterolemia, the association between G6PD deficiency and RVO, CRVO, or BRVO remained statistically significant. Similar results were obtained after adjustment for systolic or diastolic blood pressure, plasma glucose, and cholesterol levels. However, when the patients with CRVO or BRVO were categorized by gender, a significant association was found only in the women. The frequency of G6PD deficiency in patients with RVO was significantly lower than expected. The results suggest that G6PD-deficient patients have a significantly decreased risk of development of RVO in the Sardinian population.


A Generalized Coherence Framework for Detecting and Characterizing Nonlinear Interactions in the Nervous System.
This paper introduces a generalized coherence framework for detecting and characterizing nonlinear interactions in the nervous system, namely cross-spectral coherence (CSC). CSC can detect different types of nonlinear interactions including harmonic and intermodulation coupling as present in static nonlinearities and also subharmonic coupling, which only occurs with dynamic nonlinearities. We verified the performance of CSC in model simulations with both static and dynamic nonlinear systems. We applied CSC to investigate nonlinear stimulus-response interactions in the human proprioceptive system. A periodic movement perturbation was imposed to the wrist when the subjects performed an isotonic wrist flexion. CSC analysis was performed between the perturbation and brain responses (electroencephalogram, EEG). Both the simulation and the application demonstrated that CSC successfully detected different types of nonlinear interactions. High-order nonlinearities were revealed in the proprioceptive system, shown in harmonic and intermodulation coupling between the perturbation and EEG for all subjects. Subharmonic coupling was found in some subjects but not all. This paper provides a general tool to detect and characterize nonlinear nature and dynamics of the nervous system. The application of CSC on the experimental dataset indicates a complex nonlinear dynamics in the proprioceptive system. This novel framework 1) unveils the nonlinear neural dynamics in a more complete way than the existing coherence measures, and 2) is more suitable for estimating the input-output relation regarding both phase and amplitude compared to phase synchrony measures (which only consider phase coupling). Subharmonic coupling is reported in human proprioceptive system for the first time.


Association of DSM-IV Posttraumatic Stress Disorder With Traumatic Experience Type and History in the World Health Organization World Mental Health Surveys.
Previous research has documented significant variation in the prevalence of posttraumatic stress disorder (PTSD) depending on the type of traumatic experience (TE) and history of TE exposure, but the relatively small sample sizes in these studies resulted in a number of unresolved basic questions. To examine disaggregated associations of type of TE history with PTSD in a large cross-national community epidemiologic data set. The World Health Organization World Mental Health surveys assessed 29 TE types (lifetime exposure, age at first exposure) with DSM-IV PTSD that was associated with 1 randomly selected TE exposure (the random TE) for each respondent. Surveys were administered in 20 countries (n = 34 676 respondents) from 2001 to 2012. Data were analyzed from October 1, 2015, to September 1, 2016. Prevalence of PTSD assessed with the Composite International Diagnostic Interview. Among the 34 676 respondents (55.4% [SE, 0.6%] men and 44.6% [SE, 0.6%] women; mean [SE] age, 43.7 [0.2] years), lifetime TE exposure was reported by a weighted 70.3% of respondents (mean [SE] number of exposures, 4.5 [0.04] among respondents with any TE). Weighted (by TE frequency) prevalence of PTSD associated with random TEs was 4.0%. Odds ratios (ORs) of PTSD were elevated for TEs involving sexual violence (2.7; 95% CI, 2.0-3.8) and witnessing atrocities (4.2; 95% CI, 1.0-17.8). Prior exposure to some, but not all, same-type TEs was associated with increased vulnerability (eg, physical assault; OR, 3.2; 95% CI, 1.3-7.9) or resilience (eg, participation in sectarian violence; OR, 0.3; 95% CI, 0.1-0.9) to PTSD after the random TE. The finding of earlier studies that more general history of TE exposure was associated with increased vulnerability to PTSD across the full range of random TE types was replicated, but this generalized vulnerability was limited to prior TEs involving violence, including participation in organized violence (OR, 1.3; 95% CI, 1.0-1.6), experience of physical violence (OR, 1.4; 95% CI, 1.2-1.7), rape (OR, 2.5; 95% CI, 1.7-3.8), and other sexual assault (OR, 1.6; 95% CI, 1.1-2.3). The World Mental Health survey findings advance understanding of the extent to which PTSD risk varies with the type of TE and history of TE exposure. Previous findings about the elevated PTSD risk associated with TEs involving assaultive violence was refined by showing agreement only for repeated occurrences. Some types of prior TE exposures are associated with increased resilience rather than increased vulnerability, connecting the literature on TE history with the literature on resilience after adversity. These results are valuable in providing an empirical rationale for more focused investigations of these specifications in future studies.


A soft/hard magnetic nanostructure based on multisegmented CoNi nanowires.
In this paper we have introduced a new soft/hard nanostructure based on multisegmented CoNi nanowire arrays having diameters of around 110 nm and made of five segments with nominal compositions of Co, Co66Ni33, Co50Ni50, Co33Ni66 and Ni, each of which has a length of 800 nm, so that the total length of the multisegmented nanowire is 4 μm. These arrays have been synthesized by means of potentiostatic electrodeposition into the pores of hard-anodic alumina templates. The morphology, chemical composition and microstructure of the multisegmented CoNi nanowires were determined by high-resolution scanning electron microscopy, energy dispersive X-ray microanalysis, and powder X-ray diffraction method, respectively. The room temperature magnetic behavior of the multisegmented nanowire arrays is also studied and compared with CoNi nanowire arrays with homogeneous composition (non-segmented nanowires), synthesized in the same templates and having the same dimensions as the segmented ones. These nanostructures could be used to control the movement of magnetic domain walls. In this way, these nanostructures can be an alternative to store information or even perform logic functions.


The gene structure of Xenopus nuclear lamin A: a model for the evolution of A-type from B-type lamins by exon shuffling.
Nuclear lamins are intermediate filament (IF) type proteins that form a fibrillar network underlying the inner nuclear membrane. The existence of multiple subtypes of lamins in vertebrates has been interpreted in terms of functional specialization during cell division and differentiation. The structure of a gene encoding an A-type lamin of Xenopus laevis was analysed. Comparison with that of a B-type lamin of the same species shows remarkable conservation of the exon/intron pattern. In both genes the last exon, only 9-12 amino acids in length, encodes the complete information necessary for membrane targeting of lamins, i.e. a ras-related CaaX motif. The lamin A specific extension of the tail domain is encoded by a single additional exon. The 5' boundary of this exon coincides with the sequence divergence between human lamins A and C, for which an alternative splice mechanism had previously been suggested. Arguments are presented suggesting that B-type lamins represent the ancestral type of lamins and that A-type lamins derived there from by exon shuffling. The acquisition of the new exon might explain the different fates of A- and B-types lamins during cell division.


EUS in patients with benign and malignant lymphadenopathy.
The EUS appearance of lymph nodes in patients undergoing evaluation for malignancy was studied. In 378 patients EUS characteristics were assessed: size of tumor, largest lymph node size, number of lymph nodes, distance of lymph nodes from the tumor, and on a 5-point visual analogue scale (1 = least malignant to 5 = most malignant), roundness, homogeneity, and echogenicity. A morphology score (sum of roundness, homogeneity, and echogenicity) was calculated. Findings were compared with fine needle aspiration or surgical histopathology in 238 patients. When using multivariate analysis, only lymph node size (1.4 +/- 0.1 cm vs. 1.7 +/- 0.1 cm, p = 0.001), distance from tumor (3.1 +/- 0.4 cm vs. 1.6 +/- 0.4 cm, p = 0.013), and morphology score (9.9 +/- 0.3 vs. 11.9 +/- 0.3, p = 0.001) for benign versus malignant lymph nodes (mean +/- SEM) were significant. Lymph node size was significant for esophageal cancer (p = 0.006) and other mediastinal lymph nodes (p = 0.007) but not for pancreaticobiliary malignancies (p = 0.1) or celiac lymph nodes (p = 0.4). Distance from the tumor was significant for pancreaticobiliary (p = 0.01) but not esophageal cancers (p = 0.7). Morphology was significant for all sites. The presence of at least one lymph node of 1 cm or greater within 1 cm of the tumor and with a morphology score of 14 or greater had a positive predictive value of 81% (prevalence = 13%). A morphology score of 6 or less had a negative predictive value of 92% (prevalence = 12%). Patients with malignant adenopathy have lymph nodes that are larger, closer to the primary tumor, rounder, darker, and more homogeneous than those of patients without malignant adenopathy.


The effect of cone opsin mutations on retinal structure and the integrity of the photoreceptor mosaic.
To evaluate retinal structure and photoreceptor mosaic integrity in subjects with OPN1LW and OPN1MW mutations. Eleven subjects were recruited, eight of whom have been previously described. Cone and rod density was measured using images of the photoreceptor mosaic obtained from an adaptive optics scanning light ophthalmoscope (AOSLO). Total retinal thickness, inner retinal thickness, and outer nuclear layer plus Henle fiber layer (ONL+HFL) thickness were measured using cross-sectional spectral-domain optical coherence tomography (SD-OCT) images. Molecular genetic analyses were performed to characterize the OPN1LW/OPN1MW gene array. While disruptions in retinal lamination and cone mosaic structure were observed in all subjects, genotype-specific differences were also observed. For example, subjects with "L/M interchange" mutations resulting from intermixing of ancestral OPN1LW and OPN1MW genes had significant residual cone structure in the parafovea (∼25% of normal), despite widespread retinal disruption that included a large foveal lesion and thinning of the parafoveal inner retina. These subjects also reported a later-onset, progressive loss of visual function. In contrast, subjects with the C203R missense mutation presented with congenital blue cone monochromacy, with retinal lamination defects being restricted to the ONL+HFL and the degree of residual cone structure (8% of normal) being consistent with that expected for the S-cone submosaic. The photoreceptor phenotype associated with OPN1LW and OPN1MW mutations is highly variable. These findings have implications for the potential restoration of visual function in subjects with opsin mutations. Our study highlights the importance of high-resolution phenotyping to characterize cellular structure in inherited retinal disease; such information will be critical for selecting patients most likely to respond to therapeutic intervention and for establishing a baseline for evaluating treatment efficacy.


Hemophagocytic lymphohistiocytosis in pregnancy: a case report and review of treatment options.
Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening inflammatory disorder characterized by uncontrolled proliferation and activation of histiocytes with phagocytosis of normal hematopoietic cells. A 41-year-old woman, 19 weeks pregnant with twins, and a history of Still's disease, presented with rash, fever, and headache. Laboratory studies revealed transaminitis, hyperbilirubinemia, and eventually severe neutropenia as well as elevations in ferritin, lactate dehydrogenase, and C-reactive protein. A bone marrow biopsy confirmed HLH. She declined standard HLH-treatment but responded well to high-dose corticosteroids. Her blood counts remained stable following corticosteroid taper, and she delivered healthy twin girls at 30-week gestation. Few cases of HLH during pregnancy have been reported. In some cases, the condition has proved fatal. Therefore recognizing signs and symptoms of HLH is essential to avoid treatment delay. In our case, high-dose corticosteroids alone were a safe and effective therapy for the mother and fetuses resulting in long-term disease control.


Improved microbial and sensory quality of chicken meat by treatment with lactic acid, organic acid salts and modified atmosphere packaging.
Microbial contamination and growth play important roles in spoilage and quality loss of raw poultry products. We evaluated the suitability of three commercially available organic acid based antimicrobial compounds, Purac FCC80 (l-lactic acid), Verdad N6 (buffered vinegar fermentate) and Provian K (blend of potassium acetate and diacetate) to prevent growth of the innate microbiota, reduce spoilage and enhance the sensory quality of raw chicken under vacuum, high CO2 (60/40% CO2/N2), and high O2 (75/25% O2/CO2) modified atmosphere (MA) storage conditions. Solutions were applied warm (50 °C) or cold (4 °C) to reflect treatments prior to (Prechill) or after (Postchill) cooling of chicken carcasses, respectively. Single postchill treatments of raw chicken wings with 5% Verdad N6 or Provian K solutions and MA storage enabled complete growth inhibition during the first seven days of storage before growth resumed. Enhanced bacterial control was obtained by combining Prechill lactic acid and Postchill Verdad N6 or Provian K treatments which indicated initial reductions up to 1.1 log and where total bacterial increase after 20 days storage was limited to 1.8-2.1 log. Antibacterial effects were dependent on the concentration of the inhibiting salts used, pH and the storage conditions. Bacterial community analyses showed increased relative levels of Gram-positive bacteria and with reductions of potential spoilage organisms in samples treated with the organic acid salts Verdad N6 and Provian K. Sensory analyses of raw, treated wings showed prominent lower scores in several spoilage associated odour attributes when compared with untreated chicken wings after 13 days storage. For heat-treated chicken, only minor differences for 22 tested attributes were detected between seven antimicrobial treatments and untreated control chicken. Immersion in commercially available organic acid/salt solutions combined with MA storage can reduce bacterial levels, improve microbial and sensory quality, and potentially improve shelf life and reduce food waste of chicken products.


ParB dynamics and the critical role of the CTD in DNA condensation unveiled by combined force-fluorescence measurements.
Bacillus subtilis ParB forms multimeric networks involving non-specific DNA binding leading to DNA condensation. Previously, we found that an excess of the free C-terminal domain (CTD) of ParB impeded DNA condensation or promoted decondensation of pre-assembled networks (Fisher et al., 2017). However, interpretation of the molecular basis for this phenomenon was complicated by our inability to uncouple protein binding from DNA condensation. Here, we have combined lateral magnetic tweezers with TIRF microscopy to simultaneously control the restrictive force against condensation and to visualise ParB protein binding by fluorescence. At non-permissive forces for condensation, ParB binds non-specifically and highly dynamically to DNA. Our new approach concluded that the free CTD blocks the formation of ParB networks by heterodimerisation with full length DNA-bound ParB. This strongly supports a model in which the CTD acts as a key bridging interface between distal DNA binding loci within ParB networks.


Cannabinoid pharmacology and therapy in gut disorders.
Cannabis sp. and their products (marijuana, hashish…), in addition to their recreational, industrial and other uses, have a long history for their use as a remedy for symptoms related with gastrointestinal diseases. After many reports suggesting these beneficial effects, it was not surprising to discover that the gastrointestinal tract expresses endogenous cannabinoids, their receptors, and enzymes for their synthesis and degradation, comprising the so-called endocannabinoid system. This system participates in the control of tissue homeostasis and important intestinal functions like motor and sensory activity, nausea, emesis, the maintenance of the epithelial barrier integrity, and the correct cellular microenvironment. Thus, different cannabinoid-related pharmacological agents may be useful to treat the main digestive pathologies. To name a few examples, in irritable bowel syndrome they may normalize dysmotility and reduce pain, in inflammatory bowel disease they may decrease inflammation, and in colorectal cancer, apart from alleviating some symptoms, they may play a role in the regulation of the cell niche. This review summarizes the main recent findings on the role of cannabinoid receptors, their synthetic or natural ligands and their metabolizing enzymes in normal gastrointestinal function and in disorders including irritable bowel syndrome, inflammatory bowel disease, colon cancer and gastrointestinal chemotherapy-induced adverse effects (nausea/vomiting, constipation, diarrhea).


Multiclass discovery in array data.
A routine goal in the analysis of microarray data is to identify genes with expression levels that correlate with known classes of experiments. In a growing number of array data sets, it has been shown that there is an over-abundance of genes that discriminate between known classes as compared to expectations for random classes. Therefore, one can search for novel classes in array data by looking for partitions of experiments for which there are an over-abundance of discriminatory genes. We have previously used such an approach in a breast cancer study. We describe the implementation of an unsupervised classification method for class discovery in microarray data. The method allows for discovery of more than two classes. We applied our method on two published microarray data sets: small round blue cell tumors and breast tumors. The method predicts relevant classes in the data sets with high success rates. We conclude that the proposed method is accurate and efficient in finding biologically relevant classes in microarray data. Additionally, the method is useful for quality control of microarray experiments. We have made the method available as a computer program.


Exploring genetic variation in the tomato (Solanum section Lycopersicon) clade by whole-genome sequencing.
We explored genetic variation by sequencing a selection of 84 tomato accessions and related wild species representative of the Lycopersicon, Arcanum, Eriopersicon and Neolycopersicon groups, which has yielded a huge amount of precious data on sequence diversity in the tomato clade. Three new reference genomes were reconstructed to support our comparative genome analyses. Comparative sequence alignment revealed group-, species- and accession-specific polymorphisms, explaining characteristic fruit traits and growth habits in the various cultivars. Using gene models from the annotated Heinz 1706 reference genome, we observed differences in the ratio between non-synonymous and synonymous SNPs (dN/dS) in fruit diversification and plant growth genes compared to a random set of genes, indicating positive selection and differences in selection pressure between crop accessions and wild species. In wild species, the number of single-nucleotide polymorphisms (SNPs) exceeds 10 million, i.e. 20-fold higher than found in most of the crop accessions, indicating dramatic genetic erosion of crop and heirloom tomatoes. In addition, the highest levels of heterozygosity were found for allogamous self-incompatible wild species, while facultative and autogamous self-compatible species display a lower heterozygosity level. Using whole-genome SNP information for maximum-likelihood analysis, we achieved complete tree resolution, whereas maximum-likelihood trees based on SNPs from ten fruit and growth genes show incomplete resolution for the crop accessions, partly due to the effect of heterozygous SNPs. Finally, results suggest that phylogenetic relationships are correlated with habitat, indicating the occurrence of geographical races within these groups, which is of practical importance for Solanum genome evolution studies.


Gene amplification confers glyphosate resistance in Amaranthus palmeri.
The herbicide glyphosate became widely used in the United States and other parts of the world after the commercialization of glyphosate-resistant crops. These crops have constitutive overexpression of a glyphosate-insensitive form of the herbicide target site gene, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). Increased use of glyphosate over multiple years imposes selective genetic pressure on weed populations. We investigated recently discovered glyphosate-resistant Amaranthus palmeri populations from Georgia, in comparison with normally sensitive populations. EPSPS enzyme activity from resistant and susceptible plants was equally inhibited by glyphosate, which led us to use quantitative PCR to measure relative copy numbers of the EPSPS gene. Genomes of resistant plants contained from 5-fold to more than 160-fold more copies of the EPSPS gene than did genomes of susceptible plants. Quantitative RT-PCR on cDNA revealed that EPSPS expression was positively correlated with genomic EPSPS relative copy number. Immunoblot analyses showed that increased EPSPS protein level also correlated with EPSPS genomic copy number. EPSPS gene amplification was heritable, correlated with resistance in pseudo-F(2) populations, and is proposed to be the molecular basis of glyphosate resistance. FISH revealed that EPSPS genes were present on every chromosome and, therefore, gene amplification was likely not caused by unequal chromosome crossing over. This occurrence of gene amplification as an herbicide resistance mechanism in a naturally occurring weed population is particularly significant because it could threaten the sustainable use of glyphosate-resistant crop technology.


Environmentally-relevant forms of the prion protein.
Scrapie and chronic wasting disease (CWD) are prion diseases of particular environmental concern as they are horizontally transmissible and can remain infectious after years in the environment. Recent evidence suggests that the N-terminus of PrPSC, the infectious conformation of the prion protein, plays an important role in the mechanism of sorption to soil particles. We hypothesize that, in a prion-infected animal carcass, a portion of the N-terminus of PrPSc could be cleaved by proteinases in the brain at ordinary temperatures. Hamster (HY transmissible mink encephalopathy-infected), transgenic mice (CWD-infected), and elk (CWD-infected) brain homogenates were incubated at 22 and 37 degrees C for up to 1 month and then analyzed by Western blot using N-terminal and middle region monoclonal anti-PrP antibodies. For all three systems, there was a very faint or undetectable N-terminal PrP signal after 35 days at both temperatures, which indicates that full-length PrPSc might be rare in the brain matter of animal carcasses. Future studies on prion-soil interactions should therefore consider N-terminal-degraded PrPSc in addition to the full-length form. Both mouse and elk CWD PrPSc demonstrated greater resistance to degradation than HY TME PrPSc. This indicates that the transgenic mouse-CWD model is a good surrogate for natural CWD prions, but that other rodent prion models might not accurately represent CWD prion fate in the environment.


Antibody responses and epitope specificities to the Taenia solium cysticercosis vaccines TSOL18 and TSOL45-1A.
Taenia solium is a cestode parasite that causes cysticercosis in humans and pigs. This study examined the antibody responses in pigs immunized with the TSOL18 and TSOL45-1A recombinant vaccines against T. solium cysticercosis. Immunization with these proteins induced specific, complement-fixing antibodies against the recombinant antigens that are believed to be associated with vaccine-induced protection against T. solium infection. Sera from immunized pigs were used to define the linear B-cell epitopes of TSOL18 and TSOL45-1A. Prominent reactivity was revealed to one linear epitope on TSOL18 and two linear epitopes on TSOL45-1A. These, and oncosphere antigens from other taeniid cestodes, contain a protein sequence motif suggesting that they may show a tertiary structure similar to the fibronectin type III domain (FnIII). Comparison of the location of linear antigenic epitopes in TSOL18 and TSOL45-1A within the proposed FnIII structure to those within related cestode vaccine antigens reveals conservation in the positioning of the epitopes between oncosphere antigens from different taeniid species.


Graphene oxide electrochemistry: the electrochemistry of graphene oxide modified electrodes reveals coverage dependent beneficial electrocatalysis.
The modification of electrode surfaces is widely implemented in order to try and improve electron transfer kinetics and surface interactions, most recently using graphene related materials. Currently, the use of 'as is' graphene oxide (GO) has been largely overlooked, with the vast majority of researchers choosing to reduce GO to graphene or use it as part of a composite electrode. In this paper, 'as is' GO is explored and electrochemically characterized using a range of electrochemical redox probes, namely potassium ferrocyanide(II), N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD), dopamine hydrochloride and epinephrine. Furthermore, the electroanalytical efficacy of GO is explored towards the sensing of dopamine hydrochloride and epinephrine via cyclic voltammetry. The electrochemical response of GO is benchmarked against pristine graphene and edge plane-/basal plane pyrolytic graphite (EPPG and BPPG respectively) alternatives, where the GO shows an enhanced electrochemical/electroanalytical response. When using GO as an electrode material, the electrochemical response of the analytes studied herein deviate from that expected and exhibit altered electrochemical responses. The oxygenated species encompassing GO strongly influence and dominate the observed voltammetry, which is crucially coverage dependent. GO electrocatalysis is observed, which is attributed to the presence of beneficial oxygenated species dictating the response in specific cases, demonstrating potential for advantageous electroanalysis to be realized. Note however, that crucial coverage based regions are observed at GO modified electrodes, owing to the synergy of edge plane sites and oxygenated species. We report the true beneficial electrochemistry of GO, which has enormous potential to be beneficially used in various electrochemical applications 'as is' rather than be simply used as a precursor to making graphene and is truly a fascinating member of the graphene family.


Factors affecting the use of medical, mental health, alcohol, and drug treatment services by homeless adults.
This study describes use of medical, mental health, alcohol, and drug services by 832 adult residents of the New York City homeless shelter system and examines associations between service use during the past three months and an array of predisposing, enabling, and need factors. Utilization rates were 23% for medical services, 13% for mental health services, and 10 and 7.5% for alcohol and drug treatment services, respectively. Service contacts were more often hospitals than ambulatory care clinics. Logistic regression analyses revealed that need factors were stronger predictors of all four types of service use. Predisposing factors other than education and black ethnic status were not significant, and the enabling factor of enrollment in Medicaid and/or Medicare was significant only for use of medical and drug services. Among the need factors, measures of mental health status were analyzed as indices of distress to test a stress-utilization model of prediction for all four types of service use. While these measures did not predict use of nonmental health services, physical health problems were associated with use of all four types of services. Implications for future health services research and for service delivery to the homeless are discussed, including the need for more information on availability of services and on psychosocial and cultural characteristics of homeless persons that may affect their help-seeking behavior.


Overview of the SAMPL6 host-guest binding affinity prediction challenge.
Accurately predicting the binding affinities of small organic molecules to biological macromolecules can greatly accelerate drug discovery by reducing the number of compounds that must be synthesized to realize desired potency and selectivity goals. Unfortunately, the process of assessing the accuracy of current computational approaches to affinity prediction against binding data to biological macromolecules is frustrated by several challenges, such as slow conformational dynamics, multiple titratable groups, and the lack of high-quality blinded datasets. Over the last several SAMPL blind challenge exercises, host-guest systems have emerged as a practical and effective way to circumvent these challenges in assessing the predictive performance of current-generation quantitative modeling tools, while still providing systems capable of possessing tight binding affinities. Here, we present an overview of the SAMPL6 host-guest binding affinity prediction challenge, which featured three supramolecular hosts: octa-acid (OA), the closely related tetra-endo-methyl-octa-acid (TEMOA), and cucurbit[8]uril (CB8), along with 21 small organic guest molecules. A total of 119 entries were received from ten participating groups employing a variety of methods that spanned from electronic structure and movable type calculations in implicit solvent to alchemical and potential of mean force strategies using empirical force fields with explicit solvent models. While empirical models tended to obtain better performance than first-principle methods, it was not possible to identify a single approach that consistently provided superior results across all host-guest systems and statistical metrics. Moreover, the accuracy of the methodologies generally displayed a substantial dependence on the system considered, emphasizing the need for host diversity in blind evaluations. Several entries exploited previous experimental measurements of similar host-guest systems in an effort to improve their physical-based predictions via some manner of rudimentary machine learning; while this strategy succeeded in reducing systematic errors, it did not correspond to an improvement in statistical correlation. Comparison to previous rounds of the host-guest binding free energy challenge highlights an overall improvement in the correlation obtained by the affinity predictions for OA and TEMOA systems, but a surprising lack of improvement regarding root mean square error over the past several challenge rounds. The data suggests that further refinement of force field parameters, as well as improved treatment of chemical effects (e.g., buffer salt conditions, protonation states), may be required to further enhance predictive accuracy.


Using a family systems approach to investigate cancer risk communication within melanoma families.
The family provides an important communication nexus for information and support exchange about family cancer history, and adoption of family-wide cancer risk reduction strategies. The goals of this study were to (1) use the family systems theory to identify characteristics of this sample of families at increased risk of developing melanoma and (2) to relate familial characteristics to the frequency and style of familial risk communication. Participants were first-degree relatives (n=313) of melanoma patients, recruited into a family web-based intervention study. We used multivariable logistic regression models to analyze the association between family functioning and family communication. Most participants were female (60%), with an average age of 51 years. Fifty percent of participants reported that they spoke to their relatives about melanoma risk and people were more likely to speak to their female family members. Familial adaptation, cohesion, coping, and health beliefs were strongly associated with an open style of risk communication within families. None were associated with a blocked style of risk communication. Only cohesion and adaptation were associated with the amount of risk communication that occurred within families. Overall, individuals who came from families that were more highly cohesive, adaptable, and shared strong beliefs about melanoma risk were more likely to communicate openly about melanoma. The fact that this association was not consistent across blocked communication and communication frequency highlights the multifaceted nature of this process. Future research should focus on the interplay between different facets of communication.


Analysis of longitudinal head impact exposure and white matter integrity in returning youth football players.
The objective of this study was to characterize changes in head impact exposure (HIE) across multiple football seasons and to determine whether changes in HIE correlate with changes in imaging metrics in youth football players. On-field head impact data and pre- and postseason imaging data, including those produced by diffusion tensor imaging (DTI), were collected from youth football athletes with at least two consecutive seasons of data. ANCOVA was used to evaluate HIE variations (number of impacts, peak linear and rotational accelerations, and risk-weighted cumulative exposure) by season number. DTI scalar metrics, including fractional anisotropy, mean diffusivity, and linear, planar, and spherical anisotropy coefficients, were evaluated. A control group was used to determine the number of abnormal white matter voxels, which were defined as 2 standard deviations above or below the control group mean. The difference in the number of abnormal voxels between consecutive seasons was computed for each scalar metric and athlete. Linear regression analyses were performed to evaluate relationships between changes in HIE metrics and changes in DTI scalar metrics. There were 47 athletes with multiple consecutive seasons of HIE, and corresponding imaging data were available in a subsample (n = 19) of these. Increases and decreases in HIE metrics were observed among individual athletes from one season to the next, and no significant differences (all p > 0.05) in HIE metrics were observed by season number. Changes in the number of practice impacts, 50th percentile impacts per practice session, and 50th percentile impacts per session were significantly positively correlated with changes in abnormal voxels for all DTI metrics. These results demonstrate a significant positive association between changes in HIE metrics and changes in the numbers of abnormal voxels between consecutive seasons of youth football. Reducing the number and frequency of head impacts, especially during practice sessions, may decrease the number of abnormal imaging findings from one season to the next in youth football.


LRP10 genetic variants in familial Parkinson's disease and dementia with Lewy bodies: a genome-wide linkage and sequencing study.
Most patients with Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies do not carry mutations in known disease-causing genes. The aim of this study was to identify a novel gene implicated in the development of these disorders. Our study was done in three stages. First, we did genome-wide linkage analysis of an Italian family with dominantly inherited Parkinson's disease to identify the disease locus. Second, we sequenced the candidate gene in an international multicentre series of unrelated probands who were diagnosed either clinically or pathologically with Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. As a control, we used gene sequencing data from individuals with abdominal aortic aneurysms (who were not examined neurologically). Third, we enrolled an independent series of patients diagnosed clinically with Parkinson's disease and controls with no signs or family history of Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies from centres in Portugal, Sardinia, and Taiwan, and screened them for specific variants. We also did mRNA and brain pathology studies in three patients from the international multicentre series carrying disease-associated variants, and we did functional protein studies in in-vitro models, including neurons from induced pluripotent stem-like cells. Molecular studies were done between Jan 1, 2008, and Dec 31, 2017. In the initial kindred of ten affected Italian individuals (mean age of disease onset 59·8 years [SD 8·7]), we detected significant linkage of Parkinson's disease to chromosome 14 and nominated LRP10 as the disease-causing gene. Among the international series of 660 probands, we identified eight individuals (four with Parkinson's disease, two with Parkinson's disease dementia, and two with dementia with Lewy bodies) who carried different, rare, potentially pathogenic LRP10 variants; one carrier was found among 645 controls with abdominal aortic aneurysms. In the independent series, two of these eight variants were detected in three additional Parkinson's disease probands (two from Sardinia and one from Taiwan) but in none of the controls. Of the 11 probands from the international and independent cohorts with LRP10 variants, ten had a positive family history of disease and DNA was available from ten affected relatives (in seven of these families). The LRP10 variants were present in nine of these ten relatives, providing independent-albeit limited-evidence of co-segregation with disease. Post-mortem studies in three patients carrying distinct LRP10 variants showed severe Lewy body pathology. Of nine variants identified in total (one in the initial family and eight in stage 2), three severely affected LRP10 expression and mRNA stability (1424+5delG, 1424+5G→A, and Ala212Serfs*17, shown by cDNA analysis), four affected protein stability (Tyr307Asn, Gly603Arg, Arg235Cys, and Pro699Ser, shown by cycloheximide-chase experiments), and two affected protein localisation (Asn517del and Arg533Leu; shown by immunocytochemistry), pointing to loss of LRP10 function as a common pathogenic mechanism. Our findings implicate LRP10 gene defects in the development of inherited forms of α-synucleinopathies. Future elucidation of the function of the LRP10 protein and pathways could offer novel insights into mechanisms, biomarkers, and therapeutic targets. Stichting ParkinsonFonds, Dorpmans-Wigmans Stichting, Erasmus Medical Center, ZonMw-Memorabel programme, EU Joint Programme Neurodegenerative Disease Research (JPND), Parkinson's UK, Avtal om Läkarutbildning och Forskning (ALF) and Parkinsonfonden (Sweden), Lijf and Leven foundation, and cross-border grant of Alzheimer Netherlands-Ligue Européene Contre la Maladie d'Alzheimer (LECMA).


Acoustic responses of vestibular afferents in a model of superior canal dehiscence.
Afferents innervating the superior semicircular canal are rendered especially sensitive to acoustic stimulation when there is a dehiscence of the superior canal. Other vestibular end organs are also more sensitive to acoustic stimulation. Dehiscence of the superior semicircular canal is associated with vertigo and nystagmus caused by loud sounds (Tullio phenomenon) or changes in middle ear or intracranial pressures. The mechanisms by which acoustic stimuli act on the vestibular end organs are unclear. The nystagmus caused by acoustic stimuli generally aligns with the affected superior canal. Responses to acoustic stimuli in the superior vestibular nerves of anesthetized chinchillas were recorded before and after fenestration of the superior canal. Two acoustic response patterns were seen: rapid phase locking and slow tonic changes in firing rate. Phasic responses principally occurred in irregular afferents and tonic responses in regular afferents. Afferents from all of the vestibular end organs encountered could respond to acoustic stimuli, even before fenestration. However, fenestration lowered the thresholds for acoustic stimulation in superior canal afferents with phasic responses and increased the magnitude of tonic responses. Superior canal dehiscence may render the irregular afferents innervating the superior canal particularly sensitive to loud sounds. Rapid phase-locking responses may explain the short latency of nystagmus seen in patients with superior canal dehiscence syndrome. The mechanisms by which acoustic stimuli activate the vestibular end organs may differ from the damped endolymph motion associated with head acceleration.


Model order selection for bio-molecular data clustering.
Cluster analysis has been widely applied for investigating structure in bio-molecular data. A drawback of most clustering algorithms is that they cannot automatically detect the "natural" number of clusters underlying the data, and in many cases we have no enough "a priori" biological knowledge to evaluate both the number of clusters as well as their validity. Recently several methods based on the concept of stability have been proposed to estimate the "optimal" number of clusters, but despite their successful application to the analysis of complex bio-molecular data, the assessment of the statistical significance of the discovered clustering solutions and the detection of multiple structures simultaneously present in high-dimensional bio-molecular data are still major problems. We propose a stability method based on randomized maps that exploits the high-dimensionality and relatively low cardinality that characterize bio-molecular data, by selecting subsets of randomized linear combinations of the input variables, and by using stability indices based on the overall distribution of similarity measures between multiple pairs of clusterings performed on the randomly projected data. A chi2-based statistical test is proposed to assess the significance of the clustering solutions and to detect significant and if possible multi-level structures simultaneously present in the data (e.g. hierarchical structures). The experimental results show that our model order selection methods are competitive with other state-of-the-art stability based algorithms and are able to detect multiple levels of structure underlying both synthetic and gene expression data.


Female hormonal fluctuation and masticatory function in patients with disc displacement-a case-control study.
The aim of this case-control study was to investigate the role female hormone fluctuation plays in maximum occlusal force and masticatory performance in female subjects presenting disc displacement with reduction (DDR) and matched controls. Sixty-five subjects were initially recruited; however, 4 of them were excluded during the study. The final sample included 14 subjects with DDR taking oral contraceptives, 16 control subjects without DDR taking oral contraceptives, 14 normally cycling subjects with DDR, and 17 normally cycling subjects without DDR. DDR was diagnosed by means of the Research Diagnostic Criteria for Temporomandibular Disorders axis I, and subjects without pain were selected. Maximum occlusal force was measured bilaterally in the molar region using a force transducer, and masticatory performance was analyzed using the artificial material comminution and sieving method. Variables were evaluated in four phases of three menstrual cycles, identified by ovulation testing. Data were submitted to the Mauchly sphericity test and PROC MIXED procedure of the SAS statistical program for repeated measures. Multiple comparisons were made using the Tukey-Kramer test (P ⋜ .05). Comparisons among menstrual cycle phases showed no differences in occlusal force (P = .44) or masticatory performance (P = .09) for all volunteers. Subjects without DDR showed greater occlusal force (P = .01). No difference in occlusal force was found between subjects regardless of whether they took contraceptives (P = .15). Similarly, masticatory performance values did not differ among subjects with or without DDR (P = .09) or among those taking or not taking contraceptives (P = .29). Hormonal fluctuation did not influence mastication. Int J Prosthodont 2011;24:320-327.


Identifying the determinants of use of the G&G interventions for older adults in health and social care: protocol of a multilevel approach.
Despite aging-related losses, many older adults are able to maintain high levels of subjective well-being. However, not all older adults are able to self-manage and adapt. The GRIP&GLEAM [Dutch: GRIP&GLANS] (G&G) interventions have shown to significantly improve self-management ability, well-being and loneliness in older adults. Actual use of the evidence-based G&G interventions, however, remains limited as long as the interplay between implementation factors at different hierarchical stakeholder levels is poorly understood. The aim of the study is to identify the determinants of successful implementation of the G&G interventions. The study is performed in health and social care organizations in the northern part of the Netherlands. The degree of implementation success is operationalized by four parameters: use (yes/no), pace (time to initial use), performance (extent of use) and prolongation (intention to continue use). Based on the Fleuren model, factors at four hierarchical stakeholder levels (i.e. target group, professionals, organizations and financial-political context) are assessed at three measurement points in 2 years. The nested data are analyzed applying multilevel modeling techniques. In this study, health and social care organizations are considered to be part of multilevel functional systems, in which factors at different hierarchical stakeholder levels impede or facilitate use of the G&G interventions. Strengths of the study are the multifaceted measurement of use, and the multilevel approach in identifying the determinants. The study will contribute to the development of ecologically valid implementation strategies of the G&G interventions and comparable evidence-based practices.


Controlling for contamination in re-sequencing studies with a reproducible web-based phylogenetic approach.
Polymorphism discovery is a routine application of next-generation sequencing technology where multiple samples are sent to a service provider for library preparation, subsequent sequencing, and bioinformatic analyses. The decreasing cost and advances in multiplexing approaches have made it possible to analyze hundreds of samples at a reasonable cost. However, because of the manual steps involved in the initial processing of samples and handling of sequencing equipment, cross-contamination remains a significant challenge. It is especially problematic in cases where polymorphism frequencies do not adhere to diploid expectation, for example, heterogeneous tumor samples, organellar genomes, as well as during bacterial and viral sequencing. In these instances, low levels of contamination may be readily mistaken for polymorphisms, leading to false results. Here we describe practical steps designed to reliably detect contamination and uncover its origin, and also provide new, Galaxy-based, readily accessible computational tools and workflows for quality control. All results described in this report can be reproduced interactively on the web as described at http://usegalaxy.org/contamination.


Germline BRCA1 mutations and loss of the wild-type allele in tumors from families with early onset breast and ovarian cancer.
The BRCA1 gene on human chromosome 17q21 is responsible for an autosomal dominant syndrome of inherited early onset breast/ovarian cancer. It is estimated that women harboring a germline BRCA1 mutation incur an 85% lifetime risk of breast cancer and a greatly elevated risk of ovarian cancer. The BRCA1 gene has recently been isolated and mutations have been found in the germline of affected individuals in linked families. Previous studies of loss of heterozygosity (LOH) in breast tumors have been carried out on sporadic tumors derived from individuals without known linkage to BRCA1 and on tumors from linked families. Loss of large regions of chromosome 17 has been observed, but these LOH events could not be unequivocally ascribed to BRCA1. We have studied 28 breast and 6 ovarian tumors from families with strong evidence for linkage between breast cancer and genetic markers flanking BRCA1. These tumors were examined for LOH using genetic markers flanking and within BRCA1, including THRA1, D17S856, EDH17B1, EDH17B2, and D17S183. Forty-six percent (16/34) of tumors exhibit LOH which includes BRCA1. In 8 of 16 tumors the parental origin of the deleted allele could be determined by evaluation of haplotypes of associated family members; in 100% of these cases, the wild-type allele was lost. In some of these families germline mutations in BRCA1 have been determined; analyses of tumors with LOH at BRCA1 have revealed that only the disease-related allele of BRCA1 was present. These data strongly support the hypothesis that BRCA1 is a tumor suppressor gene.


Estimating the Distribution of Dietary Consumption Patterns.
In the United States the preferred method of obtaining dietary intake data is the 24-hour dietary recall, yet the measure of most interest is usual or long-term average daily intake, which is impossible to measure. Thus, usual dietary intake is assessed with considerable measurement error. We were interested in estimating the population distribution of the Healthy Eating Index-2005 (HEI-2005), a multi-component dietary quality index involving ratios of interrelated dietary components to energy, among children aged 2-8 in the United States, using a national survey and incorporating survey weights. We developed a highly nonlinear, multivariate zero-inflated data model with measurement error to address this question. Standard nonlinear mixed model software such as SAS NLMIXED cannot handle this problem. We found that taking a Bayesian approach, and using MCMC, resolved the computational issues and doing so enabled us to provide a realistic distribution estimate for the HEI-2005 total score. While our computation and thinking in solving this problem was Bayesian, we relied on the well-known close relationship between Bayesian posterior means and maximum likelihood, the latter not computationally feasible, and thus were able to develop standard errors using balanced repeated replication, a survey-sampling approach.


Directing diarrhoeal disease research towards disease-burden reduction.
Despite gains in controlling mortality relating to diarrhoeal disease, the burden of disease remains unacceptably high. To refocus health research to target disease-burden reduction as the goal of research in child health, the Child Health and Nutrition Research Initiative developed a systematic strategy to rank health research options. This priority-setting exercise included listing of 46 competitive research options in diarrhoeal disease and their critical and quantitative appraisal by 10 experts based on five criteria for research that reflect the ability of the research to be translated into interventions and achieved disease-burden reduction. These criteria included the answerability of the research questions; the efficacy and effectiveness of the intervention resulting from the research; the maximal potential for disease-burden reduction of the interventions derived from the research; the affordability, deliverability, and sustainability of the intervention supported by the research; and the overall effect of the research-derived intervention on equity. Experts scored each research option independently to delineate the best investments for diarrhoeal disease control in the developing world to reduce the burden of disease by 2015. Priority scores obtained for health policy and systems research obtained eight of the top 10 rankings in overall scores, indicating that current investments in health research are significantly different from those estimated to be the most effective in reducing the global burden of diarrhoeal disease by 2015.


Donor-derived exosomes: the trick behind the semidirect pathway of allorecognition.
The passenger leukocyte hypothesis predicts that after transplantation, donor antigen-presenting cells (APCs) from the graft present donor MHC molecules to directly alloreactive T cells in lymphoid organs. However, in certain transplantation models, recent evidence contradicts this long-standing concept. New findings demonstrate that host, instead of donor, APCs play a prominent role in allosensitization against donor MHC molecules via the semidirect pathway. A similar mechanism operates in development of T-cell split tolerance to noninherited maternal antigens. Following fully mismatch skin or heart transplantation in mice, no or extremely few donor migrating APCs (i.e. conventional dendritic cells) are detected in the draining lymphoid organs. Instead, recipient dendritic cells that have captured donor extracellular vesicles (i.e. exosomes) carrying donor MHC molecules and APC costimulatory signals present donor MHC molecules to directly alloreactive T cells. This semidirect pathway can also give rise to a form of 'split' tolerance during chronic alloantigen exposure, as indirectly alloreactive T helper cells and directly alloreactive T-cell effectors are differentially impacted by host dendritic cells 'cross-dressed' with extracellular vesicles/exosomes derived from maternal microchimerism. Acquisition by recipient APCs of donor exosomes (and likely other extracellular vesicles) released by passenger leukocytes or the graft explains the potent T-cell allosensitization against donor MHC molecules, in the absence or presence of few passenger leukocytes in lymphoid organs. It also provides the basic mechanism and in-vivo relevance of the elusive semidirect pathway. Its degree of coordination with the allopeptide - specific, indirect pathway of T-cell help may determine whether semidirect allopresentation results in a sustained, effective, acute rejection response, or rather, in abortive acute rejection and 'split' tolerance.


Using the logarithm of odds to define a vector space on probabilistic atlases.
The logarithm of the odds ratio (LogOdds) is frequently used in areas such as artificial neural networks, economics, and biology, as an alternative representation of probabilities. Here, we use LogOdds to place probabilistic atlases in a linear vector space. This representation has several useful properties for medical imaging. For example, it not only encodes the shape of multiple anatomical structures but also captures some information concerning uncertainty. We demonstrate that the resulting vector space operations of addition and scalar multiplication have natural probabilistic interpretations. We discuss several examples for placing label maps into the space of LogOdds. First, we relate signed distance maps, a widely used implicit shape representation, to LogOdds and compare it to an alternative that is based on smoothing by spatial Gaussians. We find that the LogOdds approach better preserves shapes in a complex multiple object setting. In the second example, we capture the uncertainty of boundary locations by mapping multiple label maps of the same object into the LogOdds space. Third, we define a framework for non-convex interpolations among atlases that capture different time points in the aging process of a population. We evaluate the accuracy of our representation by generating a deformable shape atlas that captures the variations of anatomical shapes across a population. The deformable atlas is the result of a principal component analysis within the LogOdds space. This atlas is integrated into an existing segmentation approach for MR images. We compare the performance of the resulting implementation in segmenting 20 test cases to a similar approach that uses a more standard shape model that is based on signed distance maps. On this data set, the Bayesian classification model with our new representation outperformed the other approaches in segmenting subcortical structures.


Pregnancy by Assisted Reproductive Technology Is Associated with Shorter Telomere Length in Neonates.
Telomere length (TL) influences the development of lifestyle-related diseases, and neonatal TL may influence their prevalence. Various factors have been reported to affect neonatal TL. Although the fetus is exposed to multiple conditions in utero, the main factors affecting the shortening of neonatal TL are still not known. In this study, we sought to identify factors that influence fetal TL. A total of 578 mother-newborn pairs were included for TL analysis. TL was measured in genomic DNA extracted from cord blood samples using quantitative PCR. The clinical factors examined at enrollment included the following intrauterine environmental factors: maternal age, assisted reproductive technology (ART) used, body mass index (BMI), gestational diabetes mellitus (GDM), maternal stress, smoking, alcohol consumption, preterm delivery, small-for-gestational-age, neonatal sex, and placental weight. Univariate and multivariate regression analyses were used to verify the relationship between neonatal TL and these clinical factors. The median neonatal TL to single-copy gene ratio was 1.0. Pregnancy with ART was among the 11 factors associated with shorter neonatal TL. From multiple regression analysis, we determined that neonatal TL was significantly shorter for pregnancies in the ART group than in the other groups. We conclude that pregnancy with ART is associated with shorter neonatal TL.


Agrobacterium-mediated viral vector-amplified transient gene expression in Nicotiana glutinosa plant tissue culture.
A viral vector based on the bean yellow dwarf virus was investigated for its potential to increase transient gene expression. An intron-containing GUS reporter gene and the cis-acting viral regulatory elements were incorporated in the viral vector and could be complemented by the viral replication-associated proteins provided on a secondary vector. All vectors were delivered to Nicotiana glutinosa plant cell suspension or hairy root cultures via auxotrophic Agrobacterium tumefaciens. Cell culture generated greater yield of reporter gene expression than did root culture, as a result of the limitation imposed on roots to express the protein only in surface tissue containing actively dividing cells. Reporter gene expression increased for cell culture when the reporter gene construct was co-delivered with the construct supplying both viral replication associated proteins (REP and REPA); gene expression decreased when the construct supplying only the viral REP protein was co-delivered. Reporter protein expression increased from 0.091% for the reporter construct alone to 0.22% total soluble protein (% TSP) when the viral Rep-supplying vector was co-delivered with the reporter gene construct. Reporter protein was generated 3 days after the initiation of bacterial co-culture, providing for rapid generation of heterologous protein in cell culture.


Quantifying the public's view on social value judgments in vaccine decision-making: A discrete choice experiment.
Vaccination programs generate direct protection, herd protection and, occasionally, side effects, distributed over different age groups. This study elicits the general public's view on how to balance these outcomes in funding decisions for vaccines. We performed an optimal design discrete choice experiment with partial profiles in a representative sample (N = 1499) of the population in the United Kingdom in November 2016. Using a panel mixed logit model, we quantified, for four different types of infectious disease, the importance of a person's age during disease, how disease was prevented-via direct vaccine protection or herd protection-and whether the vaccine induced side effects. Our study shows clear patterns in how the public values vaccination programs. These diverge from the assumptions made in public health and cost-effectiveness models that inform decision-making. We found that side effects and infections in newborns and children were of primary importance to the perceived value of a vaccination program. Averting side effects was, in any age group, weighted three times as important as preventing an identical natural infection in a child whereas the latter was weighted six times as important as preventing the same infection in elderly aged 65-75 years. These findings were independent of the length or severity of the disease, and were robust across respondents' backgrounds. We summarize these patterns in a set of preference weights that can be incorporated into future models. Although the normative significance of these weights remains a matter open for debate, our study can, hopefully, contribute to the evaluation of vaccination programs beyond cost-effectiveness.


A probabilistic computational model of cross-situational word learning.
Words are the essence of communication: They are the building blocks of any language. Learning the meaning of words is thus one of the most important aspects of language acquisition: Children must first learn words before they can combine them into complex utterances. Many theories have been developed to explain the impressive efficiency of young children in acquiring the vocabulary of their language, as well as the developmental patterns observed in the course of lexical acquisition. A major source of disagreement among the different theories is whether children are equipped with special mechanisms and biases for word learning, or their general cognitive abilities are adequate for the task. We present a novel computational model of early word learning to shed light on the mechanisms that might be at work in this process. The model learns word meanings as probabilistic associations between words and semantic elements, using an incremental and probabilistic learning mechanism, and drawing only on general cognitive abilities. The results presented here demonstrate that much about word meanings can be learned from naturally occurring child-directed utterances (paired with meaning representations), without using any special biases or constraints, and without any explicit developmental changes in the underlying learning mechanism. Furthermore, our model provides explanations for the occasionally contradictory child experimental data, and offers predictions for the behavior of young word learners in novel situations.


Activation of Kv7 channels with the anticonvulsant retigabine alleviates neuropathic pain behaviour in the streptozotocin rat model of diabetic neuropathy.
Diabetic peripheral neuropathy (DPN) is the most incapacitating complication of diabetes mellitus. Up to 50% of patients with DPN develop peripheral neuropathic pain (PNP). The underlying ionic and molecular mechanisms of diabetic PNP (DPNP) are poorly understood. However, voltage gated potassium (Kv7) channels which have been implicated in the pathogenesis of other types of PNP are likely to be involved. Here we examined, in the streptozotocin (STZ) rat model of DPNP, whether activating the Kv7 channels with a potent activator retigabine (ezogabine) would reverse/attenuate behavioural signs of DPNP. STZ rats exhibited behavioural indices of mechanical and heat hypersensitivity, but not cold hypersensitivity or spontaneous pain, 35 days after STZ injection. Retigabine given at a dose of 15 mg/kg (but not at 7.5 mg/kg, i.p.) significantly attenuated mechanical, but not heat hypersensitivity in DPNP rats, and was as effective as the positive control gabapentin. This analgesic effect of retigabine was completely reversed by the Kv7/M channel blocker XE991 (3 mg/kg, i.p.) indicating that the anti-allodynic effects of retigabine were mediated by Kv7 channels. In conclusion, the findings suggest that Kv7 channels are involved in DPNP pathogenesis, and that strategies that target their activation may prove to be effective in treating DPNP.


Women who kill their children.
During a 6 year period (1970-75) 89 women charged with the killing or attempted murder of their children were examined in a female remand prison. Six types of maternal filicide were distinguished: battering mothers (36 cases), mentally ill mothers (24 cases), neonaticides (11 cases), retaliating mothers (9 cases), women who killed unwanted children (8 cases) and mercy killing (1 case). Types of filicide were compared on a number of social and psychiatric characteristics and on their offence patterns and court disposals. The operation of the Infanticide Act is discussed in the light of these findings.


Trustworthy but not lust-worthy: context-specific effects of facial resemblance.
If humans are sensitive to the costs and benefits of favouring kin in different circumstances, a strong prediction is that cues of relatedness will have a positive effect on prosocial feelings, but a negative effect on sexual attraction. Indeed, positive effects of facial resemblance (a potential cue of kinship) have been demonstrated in prosocial contexts. Alternatively, such effects may be owing to a general preference for familiar stimuli. Here, I show that subtly manipulated images of other-sex faces were judged as more trustworthy by the participants they were made to resemble than by control participants. In contrast, the effects of resemblance on attractiveness were significantly lower. In the context of a long-term relationship, where both prosocial regard and sexual appeal are important criteria, facial resemblance had no effect. In the context of a short-term relationship, where sexual appeal is the dominant criterion, facial resemblance decreased attractiveness. The results provide evidence against explanations implicating a general preference for familiar-looking stimuli and suggest instead that facial resemblance is a kinship cue to which humans modulate responses in a context-sensitive manner.


Factors associated with increased cesarean risk among African American women: evidence from California, 2010.
We studied if both observed and unobserved maternal health in African American women in hospitals or communities were associated with cesarean delivery of infants. We examined the relationship between African American race and cesarean delivery among 493 433 women discharged from 255 Californian hospitals in 2010 using administrative data; we adjusted for patient comorbidities and maternal, fetal, and placental risk factors, as well as clustering of patients within hospitals. Cesarean rates were significantly higher overall for African American women than other women (unadjusted rate 36.8% vs 32.7%), as were both elective and emergency primary cesarean rates. Elevated risks persisted after risk adjustment (odds ratio generally > 1.27), but the prevalence of particular risk factors varied. Although African American women were clustered in some hospitals, the proportion of African Americans among all women delivering in a hospital was not related to its overall cesarean rate. To address the higher likelihood of elective cesarean delivery, attention needs to be given to currently unmeasured patient-level health factors, to the quality of provider-physician interactions, as well as to patient preferences.


A vesicle cell under collision with a Janus or homogeneous nanoparticle: translocation dynamics and late-stage morphology.
We investigate translocation dynamics of a vesicle cell under collision with a Janus or a homogeneous hydrophobic/hydrophilic nanoparticle. To this end, we perform dissipative particle dynamics simulation by setting the nanoparticle with different initial velocities, different chemical patterns of the surface for the nanoparticle, and different orientations (for the Janus nanoparticle). Particular attention is given to translocation dynamics, in-cell water discharge, and the late-stage morphologies of the vesicle/nanoparticle system after the collision. We observe three late-stage states for the Janus nanoparticle, and four late-stage states for the homogeneous nanoparticles. We find that the late-stage state and the associated dynamical pathway not only depend on the relative velocity but also on the chemical pattern of the nanoparticle surface, as well as on the orientation of the incident Janus nanoparticle. We have examined the time-dependent mean radius of the vesicle, the number of in-cell water beads lost from the vesicle, as well as the collision-induced pore size on the lipid membrane during the course of collision. Our simulation provides microscopic insights into the resilience of the vesicle-cell membrane and dynamical behavior of the vesicle under the attack of a foreign nanoparticle. Knowledge and insights gained through the simulation will have implication to the drug delivery with different chemical coatings.


Transcranial magnetic stimulation.
TMS is a powerful new tool with extremely interesting research and therapeutic potentials. Further understanding of the ways by which TMS changes neuronal function, especially as a function of its use parameters, will improve its ability to answer neuroscience questions as well as to treat diseases. Because of its noninvasiveness, it does not readily fit under the umbrella of neurosurgery. Nevertheless, it is important for neurosurgeons to be aware of TMS, because findings from TMS studies will have implications for neurosurgical approaches like DBS and VNS. Indeed, it is possible to think of using TMS as a potential noninvasive initial screening tool to identify whether perturbation of a circuit has short-term clinical effects. In the example of chronic refractory depression or OCD, which is generally a chronic illness, it might then follow that rather than having daily or weekly TMS for the rest of their lives, patients would have DBS electrodes implanted in the same circuit. Whatever road the future takes, TMS is an important new tool that will likely be of interest to neurosurgeons over the next 20 years and perhaps even longer.


Retrospective evaluation of bone pain palliation after samarium-153-EDTMP therapy.
The aim of this study was to evaluate the degree of metastatic bone pain palliation and medullar toxicity associated with samarium-153-EDTMP treatment. Seventy-three patients with metastatic bone pain having previously undergone therapy with samarium-153-EDTMP (1 mCi/kg) were retrospectively evaluated. Routine follow-up included pain evaluation and blood counts for 2 months after treatment. Pain was evaluated using a subjective scale (from 0 to 10) before and for 8 weeks after the treatment. Blood counts were obtained before treatment and once a week for 2 months during follow-up. Dosimetry, based upon the urinary excretion of the isotope, was estimated in 41 individuals, and the resulting radiation absorbed doses were correlated with hematological data. Reduction in pain scores of 75% to 100% was obtained in 36 patients (49%), with a decrease of 50% to 75%, 25% to 50%, and 0% to 25% in, respectively, 20 (27%), 10 (14%), and 7 (10%) patients. There was no significant relationship between the pain response and location of the primary tumor (breast or prostate cancer). Mild to moderate myelosuppression was noted in 75.3% of patients, usually with hematological recovery at 8 weeks. The mean bone marrow dose was 347 +/- 65 cGy, and only a weak correlation was found between absorbed dose and myelosuppression (Pearson coefficient = .4). Samarium-153-EDTMP is a valuable method for metastatic bone pain palliation. A mild to moderate and transitory myelosuppression is the main toxicity observed after samarium therapy, showing a weak correlation with dosimetric measures.


Septicemia associated with Stenotrophomonas maltophilia in a West African dwarf crocodile (Osteolaemus tetraspis subsp. tetraspis).
A 17-year-old male captive West African dwarf crocodile (Osteolaemus tetraspis subsp. tetraspis) died 1 month after fighting with a penmate. Abrasions were present on the head and mandible. Necropsy revealed a vegetative valvular lesion of the left atrioventricular valve, miliary foci of necrosis in the endocardium and myocardium, multiple duodenal and rectal ulcers, and serous atrophy of body fat. Stenotrophomonas maltophilia was isolated in pure culture from lung, liver, and kidney. Gram-negative bacilli were seen histologically in the valvular lesion and in foci of necrosis in the myocardium, liver, spleen, pancreas, kidney, and intestine. Septic thrombi in multiple tissues, arteritis, and pneumonia were additional histologic lesions. Findings indicated that the crocodile died from acute S. maltophilia septicemia, although the primary site of infection was not determined. Stenotrophomonas maltophilia is ubiquitous in the environment and is recognized as an important nosocomial pathogen in humans.


The prevalence, awareness, and control of hypertension among workers in West Africa: a systematic review.
: Interventions in workplace settings are considered to be cost-effective in preventing cardiovascular diseases. A systematic review was conducted to assess the prevalence of hypertension and the level of awareness and control among workers in West Africa. A systematic search for studies on formal and informal sector workers aged ≥15 years in West Africa published between 1980 and September 2014 was undertaken using the Ovid Medline, Embase, PubMed, and Google Scholar databases. Clinical and obstetric studies and studies that did not report prevalence were excluded. Data on study settings, characteristics of workers, blood pressure (BP) levels, prevalence of hypertension, and associated demographic factors were extracted. A total of 45 studies from six countries were identified involving 30,727 formal and informal sector workers. In 40 studies with a common definition of hypertension, the prevalence ranged from 12.0% among automobile garage workers to 68.9% among traditional chiefs. In 15 of these studies, the prevalence exceeded 30%. Typically sedentary workers such as traders, bank workers, civil servants, and chiefs were at high risk. Among health care workers, the prevalence ranged from 17.5 to 37.5%. The prevalence increased with age and was higher among males and workers with higher socio-economic status. Complications of hypertension, co-morbidities, and clustering of risk factors were common. The crude prevalence of hypertension increased progressively from 12.9% in studies published in the 1980s to 34.4% in those published in 2010-2014. The proportion of hypertensives who were previously aware of their diagnosis, were on treatment or had their BP controlled was 19.6-84.0%, 0-79.2%, and 0-12.7%, respectively. Hypertensive subjects, including health workers, rarely checked their BP except when they were ill. There is a high prevalence of hypertension among West Africa's workforce, of which a significant proportion is undiagnosed, severe or complicated. The clustering of risk factors, co-morbidities, and general low awareness warrant an integrated and multisectoral approach. Models for workplace health programmes aiming to improve cardiovascular health should be extended to informal sector workers.


Daily consumption of a synbiotic yogurt decreases energy intake but does not improve gastrointestinal transit time: a double-blind, randomized, crossover study in healthy adults.
Probiotic and synbiotic products are widely marketed to healthy individuals, although potential benefits for these individuals are rarely studied. This study investigated the effect of daily consumption of a synbiotic yogurt on gastrointestinal (GI) function in a sample of healthy adults. In a randomized crossover double-blind study, 65 healthy adults consumed 200 g/day of yogurt with (synbiotic) or without (control) added probiotics (Bifidobacterium lactis Bb12, Lactobacillus acidophilus La5, Lactobacillus casei CRL431) and 4 g inulin for two 15-day treatment periods, each preceded by a 6-week washout period. GI transit time (GTT), duration of colour (DOC), GI symptoms and dietary intake were assessed and analyzed using repeated measures ANOVA, including PRE-treatment GTT as a covariate. Participants were grouped as short GTT (STT, n = 50, ≤32.7 h) or long GTT (LTT, n = 15, >32.7 h) based on their PRE-treatment GTT assessment. POST-treatment GTT and DOC were not different between synbiotic and control, and did not change from PRE-treatment, within the STT or LTT groups. There were no changes in GI symptom ratings, indicating that both yogurts were well tolerated. In STT, energy, fat and protein intakes were decreased from baseline with synbiotic (p = 0.055, p = 0.059 and p = 0.005, respectively) and dietary fibre intake was higher POST-treatment with synbiotic versus control (p = 0.0002). In LTT, decreases in energy and fat intakes with synbiotic were not significant (p = 0.14 and p = 0.18, respectively) and there were no differences in dietary fibre intake. Consuming 200 g/day of synbiotic yogurt did not significantly alter GTT in healthy adults, but was well tolerated and helped to reduce overall energy intake.


Scale-invariant structure of size fluctuations in plants.
A wide range of physical and biological systems exhibit complex behaviours characterised by a scale-invariant structure of the fluctuations in their output signals. In the context of plant populations, scaling relationships are typically allometric. In this study, we analysed spatial variation in the size of maize plants (Zea Mays L.) grown in agricultural plots at constant densities and found evidence of scaling in the size fluctuations of plants. The findings indicate that the scaling of the probability distribution of spatial size fluctuation exhibits non-Gaussian behaviour compatible with a Lévy stable process. The scaling relationships were observed for spatial scales spanning three orders of magnitude. These findings should provide additional information for the selection and development of empirically accurate models of pattern formation in plant populations.