Track way distance and cover as risk factors for lameness in Danish dairy cows.
This study investigates the effect of length and cover of track ways between barn and pasture on lameness in Danish dairy cows. We hypothesised that short track distances would be associated with a lower lameness probability of dairy cows compared to longer distances and that track ways with prepared cover (asphalt, gravel, slag, concrete, rubber) compared to no prepared cover (sand, soil and/or grass) would be associated with a lower lameness probability of dairy cows in grazing herds. In total, 2084 dairy cows from 36 herds, grazing their dairy cows during summer, were individually assessed for their lameness status. The cows were further clinically examined for claw conformation and hock integument. Information on breed and parity per cow and size per herd was extracted from a national data base. Track way distance ranged from 0 to 700 m and was categorised as (1) <165 m or (2) ≥165 m. Cover of track way was categorised as (1) prepared (asphalt, gravel, slag, concrete, and/or rubber), (2) partly prepared or (3) not prepared (soil, sand, grass) for the surface of the majority of tracks used. The effect of track way distance and cover was evaluated for their impact on lameness using logistic analysis with a multi-level model structure. The probability for lameness did not change with track distance but increased with no (odds 4.0 times higher) or only partly prepared (odds 3.8 times higher) cover compared to prepared cover. In conclusion, we found that having a cover on the track way was associated with decreased severe lameness in Danish dairy cows.


Migraine and risk of stroke.
Migraine and stroke are two common and heterogeneous neurovascular disorders responsible for a significant burden for those affected and a great economic cost for the society. There is growing evidence that migraine increases the overall risk of cerebrovascular diseases. In this review, based on available literature through a PubMed search, we found that ischaemic stroke in people with migraine is strongly associated with migraine with aura, young age, female sex, use of oral contraceptives and smoking habits. The risk of transient ischaemic attack also seems to be increased in people with migraine, although this issue has not been extensively investigated. Although migraine appears to be associated with haemorrhagic stroke, the migraine aura status has a small influence on this relationship. Neuroimaging studies have revealed a higher prevalence of asymptomatic structural brain lesions in people with migraine. They are also more likely to have unfavourable vascular risk factors; however, the increased risk of stroke seems to be more apparent among people with migraine without traditional risk factors. The mechanism behind the migraine-stroke association is unknown. In light of the higher risk of stroke in people with migraine with aura, it is important to identify and modify any vascular risk factor. There is currently no direct evidence to support that a migraine prophylactic treatment can reduce future stroke in people with migraine.


Recent evolution of the human pathogen Cryptococcus neoformans by intervarietal transfer of a 14-gene fragment.
The availability of the whole-genome sequence from the 2 known varieties of the human pathogenic fungus Cryptococcus neoformans provides an opportunity to study the relative contribution of divergence and introgression during the process of speciation in a genetically tractable organism. At the genomic level, these varieties are nearly completely syntenic, share approximately 85-90% nucleotide identity, and are believed to have diverged approximately 18 MYA. Via a comparative genomic approach, we identified a 14-gene region (approximately 40 kb) that is nearly identical between the 2 varieties that resulted from a nonreciprocal transfer event from var. grubii to var. neoformans approximately 2 MYA. The majority of clinical and environmental var. neoformans strains from around the world contain this sequence obtained from var. grubii. This introgression event likely occurred via an incomplete intervarietal sexual cycle, creating a hybrid intermediate where mobile elements common to both lineages mediated the exchange. The subsequent duplication in laboratory strains of a fragment of this same genomic region supports evolutionary theories that instabilities in subtelomeric regions promote adaptive evolution through gene amplification and subsequent adaptation. Along with a more ancient predicted transfer event in C. neoformans and a recently reported example from Saccharomyces cerevisiae, these data indicate that DNA exchange between closely related sympatric varieties or species may be a recurrent theme in the evolution of fungal species. It further suggests that although evolutionary divergence is the primary force driving speciation, rare introgression events also play a potentially important role.


Clinical and microbiological characteristics of Bartholin gland abscesses.
To examine the clinical course and causative microorganisms of Bartholin gland abscesses. This was a retrospective study of all patients treated for Bartholin gland abscesses between the years 2006 and 2011 at the Soroka University Medical Center, a regional medical center in southern Israel. During the study period, 219 women were admitted as a result of an abscess of the Bartholin gland, 63% of which were primary abscesses and 37% recurrent abscesses (occurrence of a second clinical event). Pus cultures were positive in 126 (61.8%) of cases. Escherichia coli was the single most frequent pathogen found (43.7%) and 10 cases (7.9%) were polymicrobial. Culture-positive cases were significantly associated with fever (25% compared with 9.3%; P=.043), leukocytosis (50.4% compared with 33.8%; P=.027), and neutrophilia (17.9% compared with 5.9%; P=.021). The odds ratio of having any of these with a positive culture was 2.4 (95% confidence interval 1.3-4.3; P=.003). In the recurrent group, 81% recurred ipsilaterally and the mean time for recurrence was 32 ± 50 months. Infection with E coli was significantly more common in recurrent infection compared with primary infections (56.8% compared with 37%; P=.033). Three cases of resistance to most beta-lactam antimicrobials (extended-spectrum beta-lactamase-producing [E coli] strains) were identified. A substantial proportion of patients with Bartholin gland abscess are culture-positive with E coli being the single most common pathogen. Microbiological findings coupled with their clinical correlates are important parameters in the management of patients with a Bartholin gland abscess and in the selection of empirical antimicrobial treatment during the primary diagnosis. : III.


Voice problems in school-aged children following very preterm birth.
Very preterm children may be at risk of voice abnormalities (dysphonia). Risk factors previously identified in extremely preterm children include female gender, multiple intubations, complicated intubation and very low birth weight. This study sought to identify the prevalence of dysphonia in very preterm children, at school age. Children born between 23 and 32 weeks' gestation were included in this prospective observational study. Participants were randomly selected from a sample stratified by gestational age and number of intubations, and were aged between 5 and 12 years at the time of assessment. Clinical voice assessments were conducted by a speech pathologist, and a diagnosis of dysphonia was made based on the presence and severity of disturbance to the voice. Retrospective chart review identified medical and demographic characteristics. 178 participants were assessed. The prevalence of dysphonia in this cohort was 61%. 31% presenting with significant dysphonia, that is, voice disturbance of greater than mild in severity. Female gender (p=0.009), gestational age (p=0.031) and duration of intubation (p=0.021) were significantly associated with dysphonia although some preterm children with dysphonia were never intubated. Significant voice abnormalities were observed in children born at up to 32 weeks' gestation, with intubation a major contributing factor. ACTRN12613001015730.


A Variant of Crossed Pulmonary Arteries in Association with Coarctation of Aorta.
Crossed or "crisscross" pulmonary arteries (CPA) are a result of an anomalous origin and course of both the pulmonary arteries from the main pulmonary trunk in which the left pulmonary artery (PA) ostium usually lies directly superior and to the right PA ostium after which they cross each other and supply their respective lungs. This condition is usually associated with conotruncal malformations and genetic syndromes. We describe a case report of an infant, suspected to have Down syndrome, who was diagnosed with CPA and coarctation of aorta on computed tomography (CT) angiography. Our case is unusual because in our patient the right PA ostium was superior and to the left of the left PA suggesting a variant of CPA that has not been documented before. Three-dimensional (3D) CT reconstruction has shown to improve the understanding of this anomaly and its unique 3D display of various angles may enhance anatomical comprehension of such complex cases.


Lanthanide-Dependent Regulation of Methylotrophy in Methylobacteriumaquaticum Strain 22A.
Methylobacterium species are representative of methylotrophic bacteria. Their genomes usually encode two types of methanol dehydrogenases (MDHs): MxaF and XoxF. The former is a Ca2+-dependent enzyme, and the latter was recently determined to be a lanthanide-dependent enzyme that is necessary for the expression of mxaF. This finding revealed the unexpected and important roles of lanthanides in bacterial methylotrophy. In this study, we performed transcriptome sequencing (RNA-seq) analysis using M. aquaticum strain 22A grown in the presence of different lanthanides. Expression of mxaF and xoxF1 genes showed a clear inverse correlation in response to La3+. We observed downregulation of formaldehyde oxidation pathways, high formaldehyde dehydrogenase activity, and low accumulation of formaldehyde in the reaction with cells grown in the presence of La3+; this might be due to the direct oxidation of methanol to formate by XoxF1. Lanthanides induced the transcription of AT-rich genes, the function of most of which was unknown, and genes possibly related to cellular survival, as well as other MDH homologues. These results revealed not only the metabolic response toward altered primary methanol oxidation, but also the possible targets to be investigated further in order to better understand methylotrophy in the presence of lanthanides. IMPORTANCE Lanthanides have been considered unimportant for biological processes. In methylotrophic bacteria, however, a methanol dehydrogenase (MDH) encoded by xoxF was recently found to be lanthanide dependent, while the classic-type mxaFI is calcium dependent. XoxF-type MDHs are more widespread in diverse bacterial genera, suggesting their importance for methylotrophy. Methylobacterium species, representative methylotrophic and predominating alphaproteobacteria in the phyllosphere, contain both types and regulate their expression depending on the availability of lanthanides. RNA-seq analysis showed that the regulation takes place not only for MDH genes but also the subsequent formaldehyde oxidation pathways and respiratory chain, which might be due to the direct oxidation of methanol to formate by XoxF. In addition, a considerable number of genes of unknown function, including AT-rich genes, were found to be upregulated in the presence of lanthanides. This study provides first insights into the specific reaction of methylotrophic bacteria to the presence of lanthanides, emphasizing the biological relevance of this trace metal.


Gold nanoparticles: enhanced optical trapping and sensitivity coupled with significant heating.
Gold nanoparticles appear to be superior handles in optical trapping assays. We demonstrate that relatively large gold particles (R(b)=50 nm) indeed yield a sixfold enhancement in trapping efficiency and detection sensitivity as compared to similar-sized polystyrene particles. However, optical absorption by gold at the most common trapping wavelength (1064 nm) induces dramatic heating (266 degrees C/W). We determined this heating by comparing trap stiffness from three different methods in conjunction with detailed modeling. Due to this heating, gold nanoparticles are not useful for temperature-sensitive optical-trapping experiments, but may serve as local molecular heaters. Also, such particles, with their increased detection sensitivity, make excellent probes for certain zero-force biophysical assays.


The acrocallosal syndrome in first cousins: widening of the spectrum of clinical features and further support for autosomal recessive inheritance.
First cousins, related through their mothers, showed a pattern of craniofacial, brain, and limb anomalies consistent with the acrocallosal syndrome. Both patients had a defect of the corpus callosum, macrocephaly with a protruding forehead and occiput, hypertelorism, non-horizontal palpebral fissures, a small nose, notched ear lobes, and postaxial polydactyly of the hands. The boy, in addition, had hypospadias, cryptorchidism, inguinal hernias, duplication with syndactyly of the phalanges of the big toe, and a bipartite right clavicle. The girl had an arachnoidal cyst, a calvarian defect, and digitalisation of the thumbs. Motor and mental development was retarded in both patients. This observation provides further evidence of probable autosomal recessive inheritance of the acrocallosal syndrome and widens the spectrum of clinical findings and the variability of features in this rare malformation syndrome.


Proteomic study reveals a functional network of cancer markers in the G1-Stage of the breast cancer cell cycle.
Cancer cells are characterized by a deregulated cell cycle that facilitates abnormal proliferation by allowing cells to by-pass tightly regulated molecular checkpoints such as the G1/S restriction point. To facilitate early diagnosis and the identification of new drug targets, current research efforts focus on studies that could lead to the development of protein panels that collectively can improve the effectiveness of our response to the detection of a life-threatening disease. Estrogen-responsive MCF-7 cells were cultured and arrested by serum deprivation in the G1-stage of the cell cycle, and fractionated into nuclear and cytoplasmic fractions. The protein extracts were trypsinized and analyzed by liquid chromatography--mass spectrometry (MS), and the data were interpreted with the Thermo Electron Bioworks software. Biological characterization of the data, selection of cancer markers, and identification of protein interaction networks was accomplished with a combination of bioinformatics tools provided by GoMiner, DAVID and STRING. The objective of this work was to explore via MS proteomic profiling technologies and bioinformatics data mining whether randomly identified cancer markers can be associated with the G1-stage of the cell cycle, i.e., the stage in which cancer cells differ most from normal cells, and whether any functional networks can be identified between these markers and placed in the broader context of cell regulatory pathways. The study enabled the identification of over 2000 proteins and 153 cancer markers, and revealed for the first time that the G1-stage of the cell cycle is not only a rich source of cancer markers, but also a host to an intricate network of functional relationships within the majority of these markers. Three major clusters of interacting proteins emerged: (a) signaling, (b) DNA repair, and (c) oxidative phosphorylation. The identification of cancer marker regulatory components that act not alone, but within networks, represents an invaluable resource for elucidating the moxlecular mechanisms that govern the uncontrolled proliferation of cancer cells, as well as for catalyzing the development of protein panels with biomarker and drug target potential, screening tests with improved sensitivity and specificity, and novel cancer therapies aimed at pursuing multiple drug targets.


Quasi-phase-matched high-order harmonic generation using tunable pulse trains.
A simple technique for generating trains of ultrafast pulses is demonstrated in which the linear separation between pulses can be varied continuously over a wide range. These pulse trains are used to achieve tunable quasi-phase-matching of high harmonic generation over a range of harmonic orders up to the harmonic cut-off, resulting in enhancements of the harmonic intensity in excess of an order of magnitude. The peak enhancement of the harmonics is clearly shown to depend on the separation between pulses, as well as the number of pulses in the train, representing an easily tunable source of quasi-phase-matched high harmonic generation.


Effects of season on bull sperm quality in thawed samples in northern Spain.
The aim of the present study was to evaluate the possible effects of climate factors on sperm quality of Holstein dairy bulls housed in northern Spain. Semen samples from 11 Holstein dairy bulls were collected and cryopreserved in winter, spring and summer. Sperm quality parameters such as motility, morphology, plasma membrane integrity, acrosome status, mitochondrial membrane potential, DNA fragmentation index and reactive oxygen species were assessed. Samples collected in spring showed higher mean values of total and progressive motility compared with samples collected in winter. Mean values of average path velocity and straight-line velocity were higher in spring than in summer. The proportion of viable spermatozoa was higher in spring than in winter as was the proportion of viable spermatozoa with non-reacted acrosome. The proportion of live cells that were not producing superoxide or hydrogen peroxide was higher in samples collected in spring than in winter. No differences were found in sperm morphology or the DNA fragmentation index among seasons. In conclusion, results suggest that sperm quality of bulls housed in northern Spain is affected by season. Samples collected in spring appear to have better sperm quality than samples collected in other seasons.


Urinary exosomes: a reservoir for biomarker discovery and potential mediators of intrarenal signalling.
Over the last decade, there has been increasing research interest in urinary exosomes and their relationship with kidney physiology and disease. Protocols for isolating urinary exosomes have been refined and the exosomal proteome has been extensively catalogued and reported to contain proteins from the kidney's glomerulus and all sections of the nephron. In animal and human biomarker discovery studies, this proteome changes to reflect the underlying pathophysiology of certain kidney diseases. In addition to proteins, exosomes from urine have been demonstrated to contain RNA species, another new reservoir for biomarker discovery. Exosomes have the capacity to shuttle their cargo between kidney cells and change the recipient cell's proteome and function, and may represent a mechanism for cell-to-cell signalling along the nephron. Significant challenges remain; methods for urinary exosome collection need optimisation if "real-life" clinical utility is to be achieved, consensus is needed regarding normalisation of changes in exosomal protein and RNA, larger scale exosome biomarker validation studies remain to be performed, and whether exosomes signal between cells in vivo remains an intriguing, but untested, hypothesis.


Trunk extension strength and muscle activity in standing and kneeling postures.
A split-plot experimental design was used to evaluate the influence of posture, trunk angle, and rotational velocity on peak torque output and myoelectric activity during maximal trunk extension maneuvers. To determine whether the kneeling posture alters extension torque capabilities in isometric and isokinetic exercises as compared with standing. Also, to ascertain whether recruitment of trunk muscles is modified by such a postural change. Factors such as workplace geometry may force workers to adopt awkward or unusual postures in the performance of manual tasks. An understanding of the limitations placed on strength in unconventional working postures is crucial to the proper design of jobs. Twenty-one healthy male subjects (mean age = 36 years +/- 7 SD) performed 12 trunk extension exertions in standing and kneeling postures. Isometric tests were performed at 22.5 degrees, 45 degrees, and 67.5 degrees of trunk flexion. Isokinetic tests were done at three velocities: 30 degrees/sec, 60 degrees/sec, and 90 degrees/sec. Electromyographic data were collected from eight trunk muscles to assess muscle recruitment under each condition. A priori orthogonal contrasts were specified for analysis of both torque and electromyographic data. The kneeling posture was associated with a 15% decrease in peak torque output when contrasted with standing: however, no concomitant change in trunk muscle activity was evident. Trunk hyperflexion (isometric tests) and increasing rotational velocity (isokinetic tests) were associated with reduced torque in both postures. Trunk muscle activity was primarily affected by changes in trunk angle and velocity of contraction. A reduced extensor capability exists in the kneeling posture, despite equivalent trunk muscle activity. The similar activation patterns in both postures suggest that the strength deficit does not result from alterations in trunk muscle function. Rather, it may be the consequence of a reduced capability to rotate the pelvis in the kneeling posture, due to a disruption of the biomechanical linkage of the leg structures.


Comment on "Widespread RNA and DNA sequence differences in the human transcriptome".
Li et al. (Research Articles, 1 July 2011, p. 53; published online 19 May 2011) reported more than 10,000 mismatches between messenger RNA and DNA sequences from the same individuals, which they attributed to previously unrecognized mechanisms of gene regulation. We found that at least 88% of these sequence mismatches can likely be explained by technical artifacts such as errors in mapping sequencing reads to a reference genome, sequencing errors, and genetic variation.


Increased risk of injury following red and yellow cards, injuries and goals in FIFA World Cups.
To study the relationship between potentially game-disrupting incidents (PGDIs; red and yellow cards, goals and injuries) and the injury incidence in football. Prospective injury surveillance during three FIFA World Cups in 2002, 2006 and 2010. Official match statistics were obtained for all the matches played in the three tournaments. 2002, 2006 and 2010 FIFA World Cups. Team physicians at the 2002, 2006 and 2010 FIFA World Cups. Injury incidences and incidence rate ratios (IRRs). The injury incidence was significantly higher during match periods within the minute of, or during a five-minute period following a yellow card, red card, another injury or a goal (PGDIs) than during other match periods (76.7/1000 match hours; 95% CI (66.6 to 87.9) vs 54.0/1000 match hours (46.9 to 61.9), p<0.001). There were significant differences in injury incidence between different match periods, with the highest injury incidence seen in the last 15 min of the first half (p<0.001). The PGDIs (other than injury) had a tendency to increase towards the end of the game and the most frequent PGDI was a yellow card. There was a risk ratio of 1.17 (95% CI 1.08 to 1.26) for injury, per PGDI (other injuries excluded) (p<0.001), and 1.15 (95% CI 1.06 to 1.24) after adjusted match time (p<0.001). The injury incidence is high within the five minutes following a PGDI. For both team management and players, being aware of the increased risk of injury directly after a PGDI may be of clinical relevance, as it may enable them to take precautions in order to prevent injuries. There are significant differences in injury incidence between different match periods and game-related factors, such as PGDIs, appear partly to contribute to this variation.


The effect of photosensitizer on diclofenac photodegradation under simulated sunlight.
This paper studies the effect of photosensitizer (acetone, H(2)O(2), surfactant and pigment) on photodegradation of diclofenac (DCF) under simulated sunlight. The results demonstrate that degradation pathways proceed via pseudo first-order kinetics in all cases. The photodegradation rate was found to increase with increasing acetone and H(2)O(2). Surfactant and pigment inhibited the photodegradation of DCF. Finally, four kinds of main degradation products were observed by high performance liquid chromatography/mass spectrometry and their chemical structures were suggested.


Comprehensive study of mtDNA among Southwest Asian dogs contradicts independent domestication of wolf, but implies dog-wolf hybridization.
Studies of mitochondrial DNA (mtDNA) diversity indicate explicitly that dogs were domesticated, probably exclusively, in southern East Asia. However, Southwest Asia (SwAsia) has had poor representation and geographical coverage in these studies. Other studies based on archaeological and genome-wide SNP data have suggested an origin of dogs in SwAsia. Hence, it has been suspected that mtDNA evidence for this scenario may have remained undetected. In the first comprehensive investigation of genetic diversity among SwAsian dogs, we analyzed 582 bp of mtDNA for 345 indigenous dogs from across SwAsia, and compared with 1556 dogs across the Old World. We show that 97.4% of SwAsian dogs carry haplotypes belonging to a universal mtDNA gene pool, but that only a subset of this pool, five of the 10 principal haplogroups, is represented in SwAsia. A high frequency of haplogroup B, potentially signifying a local origin, was not paralleled with the high genetic diversity expected for a center of origin. Meanwhile, 2.6% of the SwAsian dogs carried the rare non-universal haplogroup d2. Thus, mtDNA data give no indication that dogs originated in SwAsia through independent domestication of wolf, but dog-wolf hybridization may have formed the local haplogroup d2 within this region. Southern East Asia remains the only region with virtually full extent of genetic variation, strongly indicating it to be the primary and probably sole center of wolf domestication. An origin of dogs in southern East Asia may have been overlooked by other studies due to a substantial lack of samples from this region.


Phylogenetic analyses of complete mitochondrial genome sequences suggest a basal divergence of the enigmatic rodent Anomalurus.
Phylogenetic relationships between Lagomorpha, Rodentia and Primates and their allies (Euarchontoglires) have long been debated. While it is now generally agreed that Rodentia constitutes a monophyletic sister-group of Lagomorpha and that this clade (Glires) is sister to Primates and Dermoptera, higher-level relationships within Rodentia remain contentious. We have sequenced and performed extensive evolutionary analyses on the mitochondrial genome of the scaly-tailed flying squirrel Anomalurus sp., an enigmatic rodent whose phylogenetic affinities have been obscure and extensively debated. Our phylogenetic analyses of the coding regions of available complete mitochondrial genome sequences from Euarchontoglires suggest that Anomalurus is a sister taxon to the Hystricognathi, and that this clade represents the most basal divergence among sampled Rodentia. Bayesian dating methods incorporating a relaxed molecular clock provide divergence-time estimates which are consistently in agreement with the fossil record and which indicate a rapid radiation within Glires around 60 million years ago. Taken together, the data presented provide a working hypothesis as to the phylogenetic placement of Anomalurus, underline the utility of mitochondrial sequences in the resolution of even relatively deep divergences and go some way to explaining the difficulty of conclusively resolving higher-level relationships within Glires with available data and methodologies.


Immunotherapy in non-small-cell lung cancer: a bridge between research and clinical practice.
Lung cancer has been historically considered a poorly immunogenic disease because of the few evidence of immune responses in affected patients and the limited efficacy of immunomodulating strategies. Recent understanding of the molecular mechanisms leading to cancer immune evasion has allowed the development of a new class of drugs called immune checkpoint inhibitors, which reactivate host responses with outstanding clinical benefits in a portion of patients with non-small-cell lung cancer. In this review, we briefly summarize the basis of immunogenicity and immune escape of cancer, with specific focus on non-small-cell lung cancer, mechanisms underlying immune checkpoint inhibitors efficacy and the most updated results on potential biomarkers, with the final aim of defining current unmet needs of immunotherapy in clinical practice.


A critical view on lactose-based drug formulation and device studies for dry powder inhalation: which are relevant and what interactions to expect?
Many years of research have not led to a profound knowledge of the mechanisms involved in the formulation and dispersion of carrier based mixtures for inhalation. Although it is well understood that the mixing is a key process in DPI carrier based formulation, there remains a limited understanding of how blending processes affect in-process material properties and the resulting distribution of the drug in the final dosage form. A great number of variables are considered relevant to the interfacial forces in adhesive mixtures, but their effects have mostly been investigated individually, without taking account of the influence they may have on each other. Interactions may be expected and without proper choices made and definitions given for all the variables involved, conclusions from studies on adhesive mixtures are of less relevance. By varying any of the variables that are not subject of the study, an opposite effect may be obtained. Currently, there is a strong focus on exploring techniques for the characterisation of drug and carrier surface properties that are believed to have an influence on the interparticulate forces in adhesive mixtures. For a number of surface properties it may be questioned whether they are really the key parameters to investigate however. Their orders of magnitude are subordinate to the effects they are supposed to have on the drug-to-carrier forces. Therefore, they seem rather indicators of other variability and their influence may be dominated by other effects. Finally, the relevance of inhaler design is often ignored. By using powerful inhalers, the effect of many variables of current concern may become less relevant. Carrier properties that are considered disadvantageous at present may even become desirable when a more appropriate type of dispersion force is applied. This can be shown for the effect of carrier surface rugosity when inertial separation forces are applied instead of the more widely applied lift and drag forces. Therefore, inhaler design should be taken into consideration when evaluating studies on adhesive mixtures. It should also become an integral part of powder formulation for inhalation.


Controlled trial of Iodosorb in chronic venous ulcers.
Cadexomer iodine (Iodosorb) is a hydrophilic starch powder containing iodine, which is a suitable dressing for granulating wounds such as venous ulcers. A total of 61 outpatients with chronic venous ulcers participated in a randomised optional crossover trial using cadexomer iodine or a standard dressing for their ulcers. The trial lasted for 24 weeks or until the ulcer had healed. Two patients withdrew during the course of the trial. Both treatments were highly effective, but the epithelium of ulcers dressed with cadexomer iodine grew again significantly faster (p less than 0.001). At the midpoint of the trial (12th week) 13 of 30 patients receiving standard treatment were changed to cadexomer iodine, while only three of 29 receiving cadexomer iodine changed to the standard dressing (p less than 0.02). In most cases ulcers were dressed and rebandaged daily by the patients themselves after instruction and supervision. This may be better than having dressings and bandages applied by professionals less regularly.


Sensitive and specific detection of the non-human sialic Acid N-glycolylneuraminic acid in human tissues and biotherapeutic products.
Humans are genetically defective in synthesizing the common mammalian sialic acid N-glycolylneuraminic acid (Neu5Gc), but can metabolically incorporate it from dietary sources (particularly red meat and milk) into glycoproteins and glycolipids of human tumors, fetuses and some normal tissues. Metabolic incorporation of Neu5Gc from animal-derived cells and medium components also results in variable contamination of molecules and cells intended for human therapies. These Neu5Gc-incorporation phenomena are practically significant, because normal humans can have high levels of circulating anti-Neu5Gc antibodies. Thus, there is need for the sensitive and specific detection of Neu5Gc in human tissues and biotherapeutic products. Unlike monoclonal antibodies that recognize Neu5Gc only in the context of underlying structures, chicken immunoglobulin Y (IgY) polyclonal antibodies can recognize Neu5Gc in broader contexts. However, prior preparations of such antibodies (including our own) suffered from some non-specificity, as well as some cross-reactivity with the human sialic acid N-acetylneuraminic acid (Neu5Ac). We have developed a novel affinity method utilizing sequential columns of immobilized human and chimpanzee serum sialoglycoproteins, followed by specific elution from the latter column by free Neu5Gc. The resulting mono-specific antibody shows no staining in tissues or cells from mice with a human-like defect in Neu5Gc production. It allows sensitive and specific detection of Neu5Gc in all underlying glycan structural contexts studied, and is applicable to immunohistochemical, enzyme-linked immunosorbent assay (ELISA), Western blot and flow cytometry analyses. Non-immune chicken IgY is used as a reliable negative control. We show that these approaches allow sensitive detection of Neu5Gc in human tissue samples and in some biotherapeutic products, and finally show an example of how Neu5Gc might be eliminated from such products, by using a human cell line grown under defined conditions. We report a reliable antibody-based method for highly sensitive and specific detection of the non-human sialic acid Neu5Gc in human tissues and biotherapeutic products that has not been previously described.


Pri sORF peptides induce selective proteasome-mediated protein processing.
A wide variety of RNAs encode small open-reading-frame (smORF/sORF) peptides, but their functions are largely unknown. Here, we show that Drosophila polished-rice (pri) sORF peptides trigger proteasome-mediated protein processing, converting the Shavenbaby (Svb) transcription repressor into a shorter activator. A genome-wide RNA interference screen identifies an E2-E3 ubiquitin-conjugating complex, UbcD6-Ubr3, which targets Svb to the proteasome in a pri-dependent manner. Upon interaction with Ubr3, Pri peptides promote the binding of Ubr3 to Svb. Ubr3 can then ubiquitinate the Svb N terminus, which is degraded by the proteasome. The C-terminal domains protect Svb from complete degradation and ensure appropriate processing. Our data show that Pri peptides control selectivity of Ubr3 binding, which suggests that the family of sORF peptides may contain an extended repertoire of protein regulators.


Breathing pattern during induced bronchoconstriction.
The breathing patterns of normal subjects monitored with respiratory inductive plethysmography were investigated after mild increases in respiratory resistance provoked by aerosolized methacholine during natural breathing and while breathing on a mouthpiece to a pneumotachograph. First, during natural breathing, comparisons of inspiratory ventilation (VI), tidal volume (VT), frequency (f), inspiratory time (TI), fractional inspiratory time (TI/TT), and mean inspiratory flow (VT/TI) were made before and after aerosolized buffered saline and methacholine in a dose that reduced specific airway conductance (sGaw) by 35% (PD35). There was a significant increase in VT/TI and VI after methacholine, whereas VT, f, TI, and TI/TT were not consistently modified by saline or methacholine. Pretreatment with bronchodilators prevented changes in respiratory resistance (Rrs) as well as in breathing pattern after PD35 methacholine. On another day, Rrs, end-expiratory lung volume level, and breathing pattern during natural breathing were monitored after administration of predetermined doses of methacholine that reduced sGaw by 25% (PD25), PD35, and 55% (PD55). Increases in VT/TI and end-expiratory lung volume level paralleled the increases in Rrs after each dose of methacholine but not with saline control. VI increased along with Rrs at the PD25 and PD35 doses but plateaued at the PD55 dose while Rrs continued to rise. There were no changes in breathing pattern in subjects who breathed on a mouthpiece to a pneumotachograph after PD55 methacholine. Thus alterations of the breathing pattern due to mild-to-moderate degrees of bronchoconstriction are characterized by progressive rises of mean inspiratory flow (an index of respiratory center drive) and end-expiratory lung volume level (a measure of pulmonary hyperinflation), but VI plateaus at the more severe degree of bronchoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)


Visualization of patient prescription history data in emergency care.
Interpreting patient's medication history from long textual data can be unwieldy especially in emergency care. We developed a real-time software application that converts one-year-long patient prescription history data into a visually appealing and information-rich timeline chart. The chart can be digested by healthcare providers quickly; hence, it could be an invaluable clinical tool when the rapid response time is crucial as in stroke or severe trauma cases. Furthermore, the visual clarity of the displayed information may help providers minimize medication errors. The tool has been deployed at the emergency department of a trauma center. Due to its popularity, we developed another version of this tool. It provides more granular drug dispensation information, which clinical pharmacists find very useful in their routine medication-reconciliation efforts.


Blood volume measurements in patients with heart failure and a preserved ejection fraction: implications for diagnosing anemia.
Racial differences in the prevalence of anemia in patients with heart failure have been noted. The diagnosis of anemia in heart failure patients can be confounded by many factors. Plasma volume expansion is one of the most prominent confounders. The authors investigated the difference of anemia prevalence using two different diagnostic techniques: peripheral hemoglobin recommended by the World Health Organization criteria and blood volume (BV) analysis. Racial disparities in the prevalence of anemia using both measures were compared. Sixty patients with heart failure and preserved ejection fraction (HFPEF) underwent measurement of BV by a radio-labeled albumin technique. Anemia was defined by both WHO criteria and by measured red blood cell volume (RBCV) >10% below ideal. Anemia was found in 67% of patients by the peripheral hemoglobin technique with no racial disparity. Only 35% of the patients had anemia by the BV analysis, with a 2-fold higher prevalence among Hispanics compared with whites and blacks. In patients with HFPEF, the diagnosis of anemia based on hemoglobin is confounded by plasma volume derangements resulting in significant overdiagnosis in this cohort. Racial differences in the rate of anemia were found. Such data could have important implications for the diagnosis and management of anemia in ethnic minorities with HFPEF.


Structural and biochemical dissection of photorespiration in hybrids differing in genome constitution between Diplotaxis tenuifolia (C3-C4) and radish (C3).
We compared the structural, biochemical, and physiological characteristics involved in photorespiration of intergeneric hybrids differing in genome constitution (DtDtR, DtDtRR, and DtRR) between the C(3)-C(4) intermediate species Diplotaxis tenuifolia (DtDt) and the C(3) species radish (Raphanus sativus; RR). The bundle sheath (BS) cells in D. tenuifolia included many centripetally located chloroplasts and mitochondria, but those of radish had only a few chloroplasts and mitochondria. In the hybrids, the numbers of chloroplasts and mitochondria, the ratio of centripetally located organelles to total organelles, and the mitochondrial size in the BS cells increased with an increase in the constitution ratio of the Dt:R genome. The P-protein of glycine decarboxylase (GDC) was confined to the BS mitochondria in D. tenuifolia, whereas in radish, it accumulated more densely in the mesophyll than in the BS mitochondria. In the hybrids, more intense accumulation of GDC in the BS relative to the mesophyll mitochondria occurred with an increase in the Dt:R ratio. These structural and biochemical features in the hybrids were reflected in the gas exchange characteristics of leaves, such as the CO(2) compensation point. Our data indicate that the leaf structure, the intercellular pattern of GDC expression, and the gas exchange characteristics of C(3)-C(4) intermediate photosynthesis are inherited in the hybrids depending on the constitution ratio of the parent genomes. Our findings also demonstrate that the apparent reduced photorespiration in C(3)-C(4) intermediate plants is mainly due to the structural differentiation of mitochondria and chloroplasts in the BS cells combined with the BS-dominant expression of GDC.


Glutamate release in parabrachial nucleus and baroreflex alterations after vagal afferent activation.
The parabrachial nucleus (PBN) is a regulatory nucleus that relays visceral information from the brain stem to the cortex. Immunohistochemical studies have shown that the levels of various neuropeptides in the PBN were changed after visceral afferent activation. Because the major transmitter relaying visceral information through the PBN is glutamate, the present study asked if glutamate release into the PBN also was changed after vagal afferent activation in anesthetized male rats. The distally crushed vagus was stimulated (50 Hz, 1-2 mA, 1 s on, 2 s off) for 2 h. Dialysates of the PBN were collected every 30 min and assayed for glutamate using high-performance liquid chromatography. Extracellular glutamate concentrations were reduced during the vagal stimulation, increased fourfold compared with prestimulated levels after the stimulation was terminated, and returned to prestimulated levels over the next 2 h poststimulation. These changes were not due to alterations in blood pressure because sodium nitroprusside infusion for the same interval resulted in a similar hypotension, but increased glutamate release. Phenylephrine and sodium nitroprusside were infused intravenously to measure the cardiac baroreflex before, during, and after vagal stimulation. The pressor (but not the depressor) response was elevated during the period of enhanced glutamate release, and the baroreflex curve was shifted to the right (increased threshold) without a change in gain. These changes in the cardiac baroreflex were reduced, but still seen, when the PBNs were dialyzed bilaterally with the glutamate antagonists MK-801 and 6-cyano-7-nitroquinoxaline-2,3-dione. Thus visceral activation alters glutamate release in the PBN and has enduring effects on cardiac baroreflex function.


Study of the soret effect in hydrocarbon chain/aromatic compound mixtures.
We studied the thermal diffusion behavior of equimolar mixtures of hydrocarbon chains in cyclohexane, p-xylene, and o-xylene experimentally and by reverse nonequilibrium molecular dynamics. The hydrocarbon chains heptane, 2,3-dimethylpentane, 2,4-dimethylpentane, 2-ethyl-3-methyl butadiene, and 2,4-dimethylpentadiene-1,3 with the same number of carbon atoms were considered in order to conserve the mass contribution and to investigate the shape influence on the Soret coefficient. Compared to the experimental data, the simulation results show the same trend. With increasing degree of branching, the Soret coefficient becomes larger. The negative Soret coefficient of the hydrocarbon chains indicates the enrichment in the warm side. We were able to find an empirical correlation between the properties of the pure components and the Soret coeffcients of the considered mixtures.


Sleep problems and cardiovascular function in children.
To assess the associations of sleep problems with 24-hour ambulatory blood pressure and cardiovascular reactivity in children. Sleep problems in 285 term-born, healthy 8-year-olds (mean [standard deviation] = 8.1 [0.3] years) were measured with a parent-rated Sleep Disturbance Scale for Children. Ambulatory blood pressure (n = 241) was measured for 24 hours (41% nonschool days) with an oscillometric device. The children (n = 274) underwent the Trier Social Stress Test for Children during which blood pressure, electrocardiography, and thoracic impedance were recorded and processed offline to give measures of cardiovascular and autonomic function. No associations were found between sleep problems and 24-hour ambulatory blood pressure. Children with sleep breathing disorders (n = 5) had higher baseline sympathetic vascular activity (p = .014) and higher heart rate (p = .044) and sympathetic cardiac activity (p = .031) in reaction to stress. Children with disorders of excessive somnolence (n = 55) had higher baseline parasympathetic activity (p = .016). None of the associations remained significant after controlling for multiple testing. Our results suggest that in a healthy community sample of prepubertal children, sleep problems are not associated with an unhealthy cardiovascular phenotype at this age. However, associations may be underestimated because of the low prevalence of sleep breathing disorders in this sample and may not generalize to older populations.


112-Tb/s space-division multiplexed DWDM transmission with 14-b/s/Hz aggregate spectral efficiency over a 76.8-km seven-core fiber.
We describe a new multicore fiber (MCF) having seven single-mode cores arranged in a hexagonal array, exhibiting low crosstalk among the cores and low loss across the C and L bands. We experimentally demonstrate a record transmission capacity of 112 Tb/s over a 76.8-km MCF using space-division multiplexing and dense wavelength-division multiplexing (DWDM). Each core carries 160 107-Gb/s polarization-division multiplexed quadrature phase-shift keying (PDM-QPSK) channels on a 50-GHz grid in the C and L bands, resulting in an aggregate spectral efficiency of 14 b/s/Hz. We further investigate the impact of the inter-core crosstalk on a 107-Gb/s PDM-QPSK signal after transmitting through the center core of the MCF when all the 6 outer cores carry same-wavelength 107-Gb/s signals with equal powers, and discuss the system implications of core-to-core crosstalk on ultra-long-haul transmission.


Economic impact of screening for bladder cancer using bladder tumor markers: a decision analysis.
The Food and Drug Administration recently approved the use of bladder markers such as BladderChek (NMP22; Matritech, Inc., Newton, MA) and UroVysion (Abbott Laboratories, Abbott Park, IL) for use in screening for bladder cancer. The purpose of this analysis was to assess the cost associated with implementing a widespread screening program using a noninvasive bladder tumor marker. Data for the accuracy of NMP22 in detecting bladder cancer was gathered from a comprehensive literature review. A decision tree analysis was constructed to evaluate the total cost of screening a low and high-risk population for bladder cancer using NMP22. Sensitivity analyses were conducted to evaluate the effect of relaxing the various assumptions in the model. Application of the model to all men, regardless of the degree of risk, rendered a cost per cancer detected of $783,913, $269,028, and $139,305 for ages 50-59, 60-69, and 70-79 years, respectively. Screening only patients at high-risk for bladder cancer (annual incidence 6%) would yield a cost per cancer detected of $3,310. Incidence of cancer and marker specificity had the highest influence on cost per cancer detected. Application of NMP22 to the entire population would render an extremely high cost per cancer detected. However, application to an appropriate high-risk target population could achieve cost per cancer detected comparable to currently used screening programs for prostate, colon, and breast cancer. Further studies are needed to assess the accuracy of bladder tumor markers in detecting bladder cancer in a completely asymptomatic cohort.


Adhesive and migratory effects of phosphophoryn are modulated by flanking peptides of the integrin binding motif.
Phosphophoryn (PP) is generated from the proteolytic cleavage of dentin sialophosphoprotein (DSPP). Gene duplications in the ancestor dentin matrix protein-1 (DMP-1) genomic sequence created the DSPP gene in toothed animals. PP and DMP-1 are phosphorylated extracellular matrix proteins that belong to the family of small integrin-binding ligand N-linked glycoproteins (SIBLINGs). Many SIBLING members have been shown to evoke various cell responses through the integrin-binding Arg-Gly-Asp (RGD) domain; however, the RGD-dependent function of PP is not yet fully understood. We demonstrated that recombinant PP did not exhibit any obvious cell adhesion ability, whereas the simultaneously purified recombinant DMP-1 did. A cell adhesion inhibitory analysis was performed by pre-incubating human osteosarcoma MG63 cells with various PP peptides before seeding onto vitronectin. The results obtained revealed that the incorporation of more than one amino acid on both sides of the PP-RGD domain was unable to inhibit the adhesion of MG63 cells onto vitronectin. Furthermore, the inhibitory activity of a peptide containing the PP-RGD domain with an open carboxyl-terminal side (H-463SDESDTNSESANESGSRGDA482-OH) was more potent than that of a peptide containing the RGD domain with an open amino-terminal side (H-478SRGDASYTSDESSDDDNDSDSH499-OH). This phenomenon was supported by the potent cell adhesion and migration abilities of the recombinant truncated PP, which terminated with Ala482. Furthermore, various point mutations in Ala482 and/or Ser483 converted recombinant PP into cell-adhesive proteins. Therefore, we concluded that the Ala482-Ser483 flanking sequence, which was detected in primates and mice, was the key peptide bond that allowed the PP-RGD domain to be sequestered. The differential abilities of PP and DMP-1 to act on integrin imply that DSPP was duplicated from DMP-1 to serve as a crucial extracellular protein for tooth development rather than as an integrin-mediated signaling molecule.


A Rhesus Monkey With a Naturally Occurring Impairment of Disparity Vergence. II. Abnormal Near Response Cell Activity in the Supraoculomotor Area.
Convergence insufficiency is a very common disorder that can have significant adverse effects on school performance. When reading, children with this disorder often experience diplopia and headaches. We have recently obtained a rhesus monkey with a naturally occurring impairment of vergence eye movements. In the companion paper, we report behavioral testing that shows a pattern of impairments similar to what clinicians observe in human children with convergence insufficiency, including a receded near point, an exophoria that increases as target distance decreases, and difficulty maintaining an appropriate vergence angle when presented with a large field stimulus at near. For the present case report, we wondered whether these behavioral deficits would be associated with abnormal discharge patterns in brainstem neurons related to vergence eye movements. Single unit activity was recorded from near and far response cells in the supraoculomotor area in the vergence-impaired monkey, while he performed a smooth vergence tracking task or fixated visual targets at different distances. We found an abnormally weak sensitivity to both vergence angle and vergence velocity. Nonetheless, these neurons modulated in association with contextually inappropriate slow vergence movements that occurred in the absence of saccades but not for slow divergence drifts that immediately followed converging saccades. Modulation of activity was more robust when additional depth cues were available. These data suggest that disorders affecting vergence eye movements may be associated with impoverished sensory input to the near and far response cells and, perhaps, aberrant tuning in vergence-related neurons.


The impact of eHealth on the quality and safety of health care: a systematic overview.
There is considerable international interest in exploiting the potential of digital solutions to enhance the quality and safety of health care. Implementations of transformative eHealth technologies are underway globally, often at very considerable cost. In order to assess the impact of eHealth solutions on the quality and safety of health care, and to inform policy decisions on eHealth deployments, we undertook a systematic review of systematic reviews assessing the effectiveness and consequences of various eHealth technologies on the quality and safety of care. We developed novel search strategies, conceptual maps of health care quality, safety, and eHealth interventions, and then systematically identified, scrutinised, and synthesised the systematic review literature. Major biomedical databases were searched to identify systematic reviews published between 1997 and 2010. Related theoretical, methodological, and technical material was also reviewed. We identified 53 systematic reviews that focused on assessing the impact of eHealth interventions on the quality and/or safety of health care and 55 supplementary systematic reviews providing relevant supportive information. This systematic review literature was found to be generally of substandard quality with regards to methodology, reporting, and utility. We thematically categorised eHealth technologies into three main areas: (1) storing, managing, and transmission of data; (2) clinical decision support; and (3) facilitating care from a distance. We found that despite support from policymakers, there was relatively little empirical evidence to substantiate many of the claims made in relation to these technologies. Whether the success of those relatively few solutions identified to improve quality and safety would continue if these were deployed beyond the contexts in which they were originally developed, has yet to be established. Importantly, best practice guidelines in effective development and deployment strategies are lacking. There is a large gap between the postulated and empirically demonstrated benefits of eHealth technologies. In addition, there is a lack of robust research on the risks of implementing these technologies and their cost-effectiveness has yet to be demonstrated, despite being frequently promoted by policymakers and "techno-enthusiasts" as if this was a given. In the light of the paucity of evidence in relation to improvements in patient outcomes, as well as the lack of evidence on their cost-effectiveness, it is vital that future eHealth technologies are evaluated against a comprehensive set of measures, ideally throughout all stages of the technology's life cycle. Such evaluation should be characterised by careful attention to socio-technical factors to maximise the likelihood of successful implementation and adoption.


Variety in intracellular diffusion during the cell cycle.
During the cell cycle, the organization of the cytoskeletal network undergoes dramatic changes. In order to reveal possible changes of the viscoelastic properties in the intracellular space during the cell cycle we investigated the diffusion of endogenous lipid granules within the fission yeast Schizosaccharomyces Pombe using optical tweezers. The cell cycle was divided into interphase and mitotic cell division, and the mitotic cell division was further subdivided in its stages. During all stages of the cell cycle, the granules predominantly underwent subdiffusive motion, characterized by an exponent alpha that is also linked to the viscoelastic moduli of the cytoplasm. The exponent alpha was significantly smaller during interphase than during any stage of the mitotic cell division, signifying that the cytoplasm was more elastic during interphase than during division. We found no significant differences in the subdiffusive exponents from granules measured in different stages of cell division. Also, our results for the exponent displayed no significant dependence on the position of the granule within the cell. The observation that the cytoplasm is more elastic during interphase than during mitotic cell division is consistent with the fact that elastic cytoskeletal elements such as microtubules are less abundantly present during cell division than during interphase.


Early conditions in the breastfeeding of premature newborn infants.
To describe the breastfeeding initial conditions for premature infants. The sample consisted on 26 mother/baby dyads. The babies had an average of 36.1 weeks corrected gestational age and were hospitalized in a Neonatal Intensive Care Unit in Southern Brazil. Data was collected from medical records, and the observation of the dyads was conducted during feeding, using the Observation and Evaluation of the Breastfeeding Protocol. Favorable and unfavorable behaviors were registered regarding position, responses, suction, affection and anatomy of the breast. After the observation, a questionnaire was applied to the mothers. The best results refer to the position of mother/child and affection and the poorer ones to the infant responses. Statistically significant correlations by the Spearman Correlations Coefficient were observed between some items of the protocol and other study variables. Most premature infants from this sample presented a satisfactory initiation on analyzed aspects referring to breastfeeding. Still, we emphasize the need of practices for breastfeeding effectiveness and its encouragement in this population.


Coded output photonic A/D converter based on photonic crystal slow-light structures.
A photonic analog-to-digital converter (PADC) utilizing a slow-light photonic crystal Mach-Zehnder interferometer (MZI) is proposed, to enable the optically coded output of a PADC with reduced device size and power consumption. Assuming an index modulation for the MZI on the Taylor's PADC structure, limiting factors in device size, speed, and effective number of bits are derived considering the signal transition time of the light and the slow light dispersion effects. Details of the device design and results of a time domain assessment of the device performance is described with discussions on the feasibility of sub-mm size, 20GS/s operation of the device having the ENOB (effective number of bits) > 5.


Left ventricular geometry and risk of incident hypertension.
Left ventricular (LV) geometry change is an independent predictor for cardiovascular disease. However, data are equivocal on the association of echocardiographic parameters of LV geometry with incident hypertension. Thus, we were to investigate the risk of hypertension according to the baseline echocardiographic parameters of LV geometry. Study participants were 12 562 Koreans without hypertension who received echocardiography as an item of health check-up. They were divided into normotensive or prehypertensive group according to baseline blood pressure. In each group, study subjects were classified by quintiles of baseline echocardiographic parameters including left ventricular mass index (LVMI), relative wall thickness (RWT), interventricular septal thickness (IVST), posterior wall thickness (PWT) and IVST plus PWT and followed up for 5 years. Cox proportional hazards model was used in calculating adjusted HRs and their 95% CI for hypertension according to each quintile group. Area under the curve (AUC) analysis (AUC [95% CI]) was performed to compare the predictability of LVMI, RWT, IVST, PWT, IVST plus PWT for hypertension. Prehypertensive group had the worse clinical and echocardiographic parameters in baseline analysis than normotensive group. The risk of hypertension significantly increased proportionally to baseline LVMI, RWT, IVST, PWI and IVST plus PWT above specific quintile levels, which was identified in both normotensive and prehypertensive group. In AUC analysis, IVST, PWT and IVST plus PWT showed a significantly increased AUC, compared with LVMI. LV geometry change was significantly associated with the increased risk for hypertension in non-hypertensive individuals.


Localization of the fragile X mental retardation 2 (FMR2) protein in mammalian brain.
The transcriptional silencing of the FMR2 gene has been implicated in FRAXE mental retardation. FRAXE individuals have been shown to exhibit learning deficits, including speech delay, reading and writing problems. FMR2 encodes a large protein of 1311 amino acids and is a member of a gene family encoding proline-serine-rich proteins that have properties of nuclear transcription factors. To characterize the expression of the fragile X mental retardation 2 (FMR2) protein, polyclonal antibodies were raised against two regions of the human FMR2 protein and used in immunofluorescence experiments on mouse brain cryosections. Our results demonstrate for the first time that the FMR2 protein is localized in neurons of the neocortex, Purkinje cells of the cerebellum and the granule cell layer of the hippocampus. FMR2 staining is shown to colocalize with the nuclear stain 4,6-diamidino-2-phenylindole (DAPI) confirming that FMR2 is a nuclear protein. The localization of FMR2 protein to the mammalian hippocampus and other brain structures involved with cognitive function is consistent with the learning deficits seen in FRAXE individuals.


Different sensitivity of isoprene emission, respiration and photosynthesis to high growth temperature coupled with drought stress in black poplar (Populus nigra) saplings.
The effects of the interaction between high growth temperatures and water stress on gas-exchange properties of Populus nigra saplings were investigated. Water stress was expressed as a function of soil water content (SWC) or fraction of transpirable soil water (FTSW). Isoprene emission and photosynthesis (A) did not acclimate in response to elevated temperature, whereas dark (R(n)) and light (R(d)) respiration underwent thermal acclimation. R(d) was ~30% lower than R(n) irrespective of growth temperature and water stress level. Water stress induced a sharp decline, but not a complete inhibition, of both R(n) and R(d). There was no significant effect of high growth temperature on the responses of A, stomatal conductance (g(s)), isoprene emission, R(n) or R(d) to FTSW. High growth temperature resulted in a significant increase in the SWC endpoint. Photosynthesis was limited mainly by CO(2) acquisition in water-stressed plants. Impaired carbon metabolism became apparent only at the FTSW endpoint. Photosynthesis was restored in about a week following rewatering, indicating transient biochemical limitations. The kinetics of isoprene emission in response to FTSW confirmed that water stress uncouples the emission of isoprene from A, isoprene emission being unaffected by decreasing g(s). The different kinetics of A, respiration and isoprene emission in response to the interaction between high temperature and water stress led to rising R(d)/A ratio and amount of carbon lost as isoprene. Since respiration and isoprene sensitivity are much lower than A sensitivity to water stress, temperature interactions with water stress may dominate poplar acclimatory capability and maintenance of carbon homeostasis under climate change scenarios. Furthermore, predicted temperature increases in arid environments may reduce the amount of soil water that can be extracted before plant gas exchange decreases, exacerbating the effects of water stress even if soil water availability is not directly affected.


Nanoporous Ca3Co4O9 Thin Films for Transferable Thermoelectrics.
The development of high-performance and transferable thin-film thermoelectric materials is important for low-power applications, e.g., to power wearable electronics, and for on-chip cooling. Nanoporous films offer an opportunity to improve thermoelectric performance by selectively scattering phonons without affecting electronic transport. Here, we report the growth of nanoporous Ca3Co4O9 thin films by a sequential sputtering-annealing method. Ca3Co4O9 is promising for its high Seebeck coefficient and good electrical conductivity and important for its nontoxicity, low cost, and abundance of its constituent raw materials. To grow nanoporous films, multilayered CaO/CoO films were deposited on sapphire and mica substrates by rf-magnetron reactive sputtering from elemental Ca and Co targets, followed by annealing at 700 °C to form the final phase of Ca3Co4O9. This phase transformation is accompanied by a volume contraction causing formation of nanopores in the film. The thermoelectric propoperties of the nanoporous Ca3Co4O9 films can be altered by controlling the porosity. The lowest electrical resistivity is ∼7 mΩ cm, yielding a power factor of 2.32 × 10-4 Wm-1K-2 near room temperature. Furthermore, the films are transferable from the primary mica substrates to other arbitrary polymer platforms by simple dry transfer, which opens an opportunity of low-temperature use these materials.


Characterization of the human ephrin-A4 promoter.
Expression of the ephrin-A4 ligand, a family member of ligands binding the Eph receptor tyrosine kinases, is induced after an antigen-receptor stimulation of lymphocytes. To understand the transcription regulation of the ephrin-A4 gene, its promoter was identified and regulating elements were characterized. The ephrin-A4 promoter contains cis elements directing the cell-specific expression. By deletion studies, three specific regions, which were contributing to the transcription activity in lymphoid cells, were localized. In one of these regions, an inverted CCAAT box was identified and shown to bind the transcription activator nuclear factor-Y (NF-Y). The importance of NF-Y binding for the ephrin-A4 promoter activity is shown by a total abrogation of promoter activity after destruction of its binding site. NF-Y binding and activity are also crucially dependent on the integrity of the surrounding sequence. In addition, electrophoretic mobility-shift assay and serial-mutation analysis of the two remaining regulating regions revealed cis regulatory elements contributing to the transcription activity of the ephrin-A4 promoter.


Predictors of Longitudinal Quality of Life in Juvenile Localized Scleroderma.
Localized scleroderma can negatively affect children's quality of life (QoL), but predictors of impact have not been well described. We sought to identify predictors of QoL impact in juvenile localized scleroderma patients. We analyzed longitudinal data from a single-center cohort of juvenile localized scleroderma patients, using hierarchical generalized linear modeling (HGLM) to identify predictors of QoL impact. HGLM is useful for nested data and allows for evaluation of both time-variant and time-invariant predictors. The number of extracutaneous manifestations (ECMs; e.g., joint contracture and hemifacial atrophy) and female sex predicted negative QoL impact, defined as a Children's Dermatology Life Quality Index score >1 (P = 0.019 for ECMs and P = 0.002 for female sex). As the time since the initial visit increased, the odds of reporting a negative QoL impact decreased (P < 0.001). Our results suggest that ECMs, sex, and time since initial visit are more predictive of QoL impact in localized scleroderma than cutaneous features. Further study is required to determine which ECMs have the most impact on QoL, which factors underlie sex differences in QoL in localized scleroderma, and why increasing the time since the initial visit appears to be protective. An improved understanding of predictors of QoL impact may allow for the identification of patients at risk of poorer outcomes and for the tailoring of treatment and psychosocial support.


Expression of genes belonging to the IGF-system in glial tumors.
Increased expression of the insulin-like growth factor (IGF) family members, IGF1, IGF2, their receptors and binding proteins, or combinations thereof has been documented in various malignancies including gliomas. The results of multiple investigations suggest that the IGFs can play a paracrine and/or autocrine role in promoting tumor growth in situ during tumor progression but that these roles may vary depending on the tissue of origin. Enhanced IGF1 expression was not found in glioblastomas and it was supposed that IGF1 participation in the development of glial tumors may be substituted by protein products of highly expressed other genes, also participating in PI3K and MAPK pathways. Increased expression of IGF-binding protein genes in brain tumors makes the picture even more complicated. As other binding proteins, IGFBPs regulate the activity of their ligands by prolonging their half-life. The discrepancies arising from conflicting evidence on the results obtained by different laboratories in human gliomas are discussed. Our data highlight the importance of viewing the IGF-related proteins as a complex multifactorial system and show that changes in the expression levels of any one component of the system, in a given malignancy, should be interpreted with caution. As IGF targeting for anticancer therapy is rapidly becoming clinical reality, an understanding of this complexity is very timely.


NCRI phase II study of CHOP in combination with ofatumumab in induction and maintenance in newly diagnosed Richter syndrome.
Richter syndrome (RS) is associated with chemotherapy resistance and a poor historical median overall survival (OS) of 8-10 months. We conducted a phase II trial of standard CHOP-21 (cyclophosphamide, doxorubicin, vincristine, prednisolone every 21 d) with ofatumumab induction (Cycle 1: 300 mg day 1, 1000 mg day 8, 1000 mg day 15; Cycles 2-6: 1000 mg day 1) (CHOP-O) followed by 12 months ofatumumab maintenance (1000 mg given 8-weekly for up to six cycles). Forty-three patients were recruited of whom 37 were evaluable. Seventy-three per cent were aged >60 years. Over half of the patients received a fludarabine and cyclophosphamide-based regimen as prior CLL treatment. The overall response rate was 46% (complete response 27%, partial response 19%) at six cycles. The median progression-free survival was 6·2 months (95% confidence interval [CI] 4·9-14·0 months) and median OS was 11·4 months (95% CI 6·4-25·6 months). Treatment-naïve and TP53-intact patients had improved outcomes. Fifteen episodes of neutropenic fever and 46 non-neutropenic infections were observed. There were no treatment-related deaths. Seven patients received platinum-containing salvage at progression, with only one patient obtaining an adequate response to proceed to allogeneic transplantation. CHOP-O with ofatumumab maintenance provides minimal benefit beyond CHOP plus rutuximab. Standard immunochemotherapy for RS remains wholly inadequate for unselected RS. Multinational trials incorporating novel agents are urgently needed.


Utility of symptoms to predict treatment outcomes in obstructive sleep apnea syndrome.
Polysomnography defines the pathophysiology of obstructive sleep apnea syndrome (OSAS) but does not predict some important comorbidities or their response to adenotonsillectomy. We assessed whether OSAS symptoms, as reflected on the Sleep-Related Breathing Disorders Scale of the Pediatric Sleep Questionnaire (PSQ), may offer clinical predictive value. Baseline and 7-month follow-up data were analyzed from 185 participants (aged 5-9 years with polysomnographically confirmed OSAS) in the surgical treatment arm of the multicenter Childhood Adenotonsillectomy Trial. Associations were assessed between baseline PSQ or polysomnographic data and baseline morbidity (executive dysfunction, behavior, quality of life, sleepiness) or postsurgical improvement. At baseline, each 1-SD increase in baseline PSQ score was associated with an adjusted odds ratio that was ∼3 to 4 times higher for behavioral morbidity, 2 times higher for reduced global quality of life, 6 times higher for reduced disease-specific quality of life, and 2 times higher for sleepiness. Higher baseline PSQ scores (greater symptom burden) also predicted postsurgical improvement in parent ratings of executive functioning, behavior, quality of life, and sleepiness. In contrast, baseline polysomnographic data did not independently predict these morbidities or their postsurgical improvement. Neither PSQ nor polysomnographic data were associated with objectively assessed executive dysfunction or improvement at follow-up. PSQ symptom items, in contrast to polysomnographic results, reflect subjective measures of OSAS-related impairment of behavior, quality of life, and sleepiness and predict their improvement after adenotonsillectomy. Although objective polysomnography is needed to diagnose OSAS, the symptoms obtained during an office visit can offer adjunctive insight into important comorbidities and likely surgical responses.


Improved Detection Rate of Ovarian Cancer Using a 2-Step Triage Model of the Risk of Malignancy Index and Expert Sonography in an Outpatient Screening Setting.
Preoperative assessment of adnexal masses with ultrasound has been shown to be time-, cost-effective, and specific. When used in combination with the menopausal status and the tumor marker CA125, the risk of malignancy index (RMI) can be calculated, allowing appropriate preoperative triage of patients to a gynecologist or a gynecological oncologist. Moreover, it allows for accurate planning of the required surgical procedure (laparoscopy vs laparotomy). A large general gynecologic ultrasonic database retrospectively identified 5218 patients for a 14-year period who presented to the outpatient clinic with an adnexal mass. Additional data (menopausal status, histology, CA125 values) were available in 1108 of these patients. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. The results were then compared with previously published data from a large Australian gynecological cancer center (GCC, n = 204). With the use of an RMI cutoff of 200, malignant ovarian tumors were correctly triaged to a gynecologic oncologist in 123 of 172 cases, leading to a sensitivity of 72% and specificity of 92% in our general outpatient clinic population compared with a sensitivity of 84% and a specificity of 77% in the GCC high-risk population. The negative predictive value was 95% compared with only 85% in the GCC cohort. We hypothesize that improvement of the overall detection rate of malignancy could be improved from 72% to 85% using a 2-step model, referring patients with an ultrasonic score of 3 to an experienced sonographer who uses pattern recognition. The RMI is an easy and reliable tool for the accurate triage of adnexal masses. Its value is higher in an unselected gynecological outpatient setting. Our proposed 2-step model including expert pattern recognition could influence particularly the detection rate in borderline and early-stage ovarian cancers and overcome the limitations of the tumor marker CA125.


Laser-assisted cataract surgery versus standard ultrasound phacoemulsification cataract surgery.
Cataract is the leading cause of blindness in the world, and cataract surgery is one of the most commonly performed operations in the Western world. Preferred surgical techniques have changed dramatically over the past half century with associated improvements in outcomes and safety. Femtosecond laser platforms that can accurately and reproducibly perform key steps in cataract surgery, including corneal incisions, capsulotomy and lens fragmentation, are now available. The potential advantages of laser-assisted surgery are broad, and include greater safety and better visual outcomes through greater precision and reproducibility. To compare the effectiveness of laser-assisted cataract surgery with standard ultrasound phacoemulsification cataract surgery by gathering evidence on safety from randomised controlled trials (RCTs). We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 4), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to May 2016), EMBASE (January 1980 to May 2016), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to May 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and the U.S. Food and Drugs Administration (FDA) website (www.fda.gov). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 10 May 2016. We included randomised controlled trials where laser-assisted cataract surgery was compared to standard ultrasound phacoemulsification cataract surgery. We graded the certainty of the evidence using GRADE. Two review authors independently screened the search results, assessed risk of bias and extracted data using the standard methodological procedures expected by Cochrane. The primary outcome for this review was intraoperative complications in the operated eye, namely anterior capsule and posterior capsule tears. The secondary outcomes were visual acuity (corrected distance visual acuity (CDVA) and uncorrected distance visual acuity (UDVA)), refractive outcomes, quality of vision (as measured by any validated visual function score), postoperative complications and cost-effectiveness. We included 16 RCTs conducted in Germary, Hungary, Italy, India, China and Brazil that enrolled a total of 1638 eyes of 1245 adult participants. Overall, the studies were at unclear or high risk of bias. In 11 of the studies the authors reported financial links with the manufacturer of the laser platform evaluated in their studies. Five of the studies were within-person (paired-eye) studies with one eye allocated to one procedure and the other eye allocated to the other procedure. These studies were reported ignoring the paired nature of the data.The number of anterior capsule and posterior capsule tears reported in the included studies for both laser cataract surgery and manual phacoemulsification cataract surgery were low. There were four anterior capsule tears and one posterior capsule tear in 1076 eyes reported in 10 studies (2 anterior capsule tears in laser arms, 2 anterior capsule tears and 1 posterior capsule tear in standard phacoemulsification arms). We are very uncertain as to the effect of laser-assisted surgery compared to standard phacoemulsification surgery with respect to these two outcomes. For postoperative cystoid macular oedema and elevated postoperative intraocular pressures, again the evidence was inconclusive (odds ratio (OR) 0.58, 95% confidence interval (CI) 0.20 to 1.68; 957 eyes, 9 studies, low certainty evidence; and OR 0.57, 95% CI 0.11 to 2.86; 903 eyes, 8 studies, low certainty evidence).We found little evidence of any important difference in postoperative visual acuity between laser-assisted and standard phacoemulsification arms. There was a small advantage for laser-assisted cataract surgery at six months in CDVA. However, the mean difference (MD) was -0.03 logMAR (95% CI -0.05 to -0.00; 224 eyes, 3 studies, low certainty evidence) which is equivalent to 1.5 logMAR letters and is therefore, clinically insignificant. No studies reported patient-reported outcome measures such as visual function.There were no data reported on costs or resource use but three studies reported the time taken to do the surgery. There was little evidence of any major difference between the two procedures in this respect (MD 0.1 minutes, 95% CI -0.02 to 0.21; 274 eyes, low certainty evidence). The evidence from the 16 randomised controlled trials RCTs included in this review could not determine the equivalence or superiority of laser-assisted cataract surgery compared to standard manual phacoemulsification for our chosen outcomes due to the low to very low certainty of the evidence available from these studies. As complications occur rarely, large, adequately powered, well designed, independent RCTs comparing the safety and efficacy of laser-assisted cataract surgery with standard phacoemulsification cataract surgery are needed. Standardised reporting of complications and visual and refractive outcomes for cataract surgery would facilitate future synthesis. Data on patient-reported outcomes and cost-effectiveness are needed. Paired-eye studies should be analysed and reported appropriately.


Self-Enhancement and Psychological Adjustment: A Meta-Analytic Review.
This article advances the debate about costs and benefits of self-enhancement (the tendency to maintain unrealistically positive self-views) with a comprehensive meta-analytic review (299 samples, N = 126,916). The review considers relations between self-enhancement and personal adjustment (life satisfaction, positive affect, negative affect, depression), and between self-enhancement and interpersonal adjustment (informant reports of domain-general social valuation, agency, communion). Self-enhancement was positively related to personal adjustment, and this relation was robust across sex, age, cohort, and culture. Important from a causal perspective, self-enhancement had a positive longitudinal effect on personal adjustment. The relation between self-enhancement and interpersonal adjustment was nuanced. Self-enhancement was positively related to domain-general social valuation at 0, but not long, acquaintance. Communal self-enhancement was positively linked to informant judgments of communion, whereas agentic self-enhancement was linked positively to agency but negatively to communion. Overall, the results suggest that self-enhancement is beneficial for personal adjustment but a mixed blessing for interpersonal adjustment.


Rescuer-limited cardiopulmonary resuscitation as an alternative to 2-min switched CPR in the setting of inhospital cardiac arrest: a randomised cross-over study.
The 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation (CPR) recommend that chest compression be rotated every 2 min to prevent rescuer fatigue. However, the quality of chest compression using 2-min switched CPR tends to decrease rapidly due to rescuer fatigue. We aimed to compare the effectiveness of use of 2-min switched CPR and rescuer-limited CPR (the person performing compressions is allowed to switch with another rescuer prior to 2 min if feeling fatigued) in the setting of inhospital cardiac arrest. Using a randomised cross-over trial design, 90 medical students were grouped into pairs to perform four cycles of 2-min switched CPR and rescuer-limited CPR (495 s per technique). During each trial, the total number of compressions performed, mean depth of compression and proportion of effective compressions performed (compression depth >5 mm) were recorded for identification of significant differences and changes in pulse rate and RR were measured to determine the extent of exhaustion. Compared with 2-min switched CPR, the mean compression was deeper (51 vs 47 mm, p<0.001), total number of compressions greater (476 vs 397, p=0.003) and proportion of effective compressions greater (56% vs 47%, p=0.004) during rescuer-limited CPR. Subgroup analysis by 30-s unit showed more consistent compression quality during rescuer-limited CPR. No significant differences in change in pulse rate and RR were found between the two techniques. Rescuer-limited CPR yields a greater number of effective compressions and more consistent quality of CPR than 2-min switched CPR. Rescuer-limited CPR might be a suitable alternative for treating inhospital cardiac arrest.


Endocytosis and chloroquine accumulation during the cell cycle of hepatoma cells in culture.
Variations of endocytic and of lysosomal functions during the cell cycle have been investigated in synchronized hepatoma cells (derived from Morris hepatoma 7288c) by following the cellular uptake of horseradish peroxidase, dextran (mol wt. 70,000), and chloroquine. Cell fractionation and cytochemistry show that in asynchronously growing cells exposed for 1 h to 5 mg/ml peroxidase, the bulk of the enzyme taken up by the cells is found in phagosomes. By using the same experimental system with synchronized HTC cells, large variations of endocytosis are observed during the cell cycle. Peroxidase uptake is lowest during mitosis, increases 5--10 times during G1 phase, reaches a plateau, and finally decreases at the end of S phase and during G2 phase. A similar evolution is observed for the uptake of dextran (0.5 or 1 mg/ml), but it is likely that a significant part of the polysaccharide is still associated with the pericellular surface after 1 h. Moreover, dextran is transferred more slowly than peroxidase to lysosomes. Cellular accumulation of chloroquine is related to intralysosomal pH or to the buffering capacity of lysosomes. Our results show that this drug is taken up more rapidly during G1 and S phases while the rate of accumulation is lowest in mitotic cells. The results are discussed in relation to the modifications of the physical properties of lysosomes during the cell cycle observed previously by cell fractionation and electron microsocopy, and to the possible role of lysosomes in the initiation of mitosis. Cyclic changes of endocytosis in actively dividing cells are demonstrated by our observations and may induce large differences in the uptake rate of extracellular substances.


1-Year Outcomes After Edge-to-Edge Valve Repair for Symptomatic Tricuspid Regurgitation: Results From the TriValve Registry.
The purpose of this study was to evaluate procedural and 1-year clinical and echocardiographic outcomes of patients treated with tricuspid edge-to-edge repair. Transcatheter edge-to-edge repair has been successfully performed in selected patients with symptomatic tricuspid regurgitation (TR) and high risk for surgery, but outcome data are sparse. This analysis of the multicenter international TriValve (Transcatheter Tricuspid Valve Therapies) registry included 249 patients with severe TR treated with edge-to-edge repair in compassionate and/or off-label use. Clinical and echocardiographic outcomes were prospectively collected and retrospectively analyzed. In 249 patients (mean age 77 ± 9 years; European System for Cardiac Operative Risk Evaluation II score 6.4% [interquartile range: 3.9% to 13.9%]), a successful procedure with TR reduction to grade ≤2+ was achieved in 77% by placement of 2 ± 1 tricuspid clips. Concomitant treatment of severe TR and mitral regurgitation was performed in 52% of patients. At 1-year follow-up, significant and durable improvements in TR severity (TR ≤2+ in 72% of patients) and New York Heart Association functional class (≤II in 69% of patients) were observed. All-cause mortality was 20%, and the combined rate of mortality and unplanned hospitalization for heart failure was 35%. Predictors of procedural failure included effective regurgitant orifice area, tricuspid coaptation gap, tricuspid tenting area, and absence of central or anteroseptal TR jet location. Predictors of 1-year mortality were procedural failure, worsening kidney function, and absence of sinus rhythm. Transcatheter tricuspid edge-to-edge repair can achieve TR reduction at 1 year, resulting in significant clinical improvement. Predictors of procedural failure and 1-year mortality identified here may help select patients who will benefit most from this therapy.


Synergistic oxidative impact of aluminum chloride and sodium fluoride exposure during early stages of brain development in the rat.
Aluminum is widely used in industry and in cooking utensils, especially in countries with low economic and social standards. Fluoride is also used in industry, a major component of toothpaste and is added to the drinking water in many countries to fight teeth decay and cavities. Consequently, the coexistence of aluminum and fluoride is highly probable. Growing evidence indicates that environmental pollutants during the early stages of embryonic development may reprogram the offspring's brain capabilities to encounter oxidative stress during the rest of their postnatal life. This study investigated the impact of sodium fluoride (NaF, 0.15 g/L) and aluminum chloride (AlCl3, 500 mg/L) added, individually or in combination, to the deionized drinking water starting from day 6 of gestation until just after weaning, or until the age of 70 days postnatal life. A significant decline was observed in tissue contents of vitamin C, reduced glutathione, GSH/GSSH ratio, and the total protein, as well as in the activities of Na+/K+-ATPase and superoxide dismutase (SOD) in almost all cases. On the contrary, lipid peroxidation and NO, as total nitrate, exhibited a significant increase in comparison with the corresponding control. Based on the present results, administration of Al and NaF, alone or in combination abated the quenching effects of the antioxidant system and induced oxidative stress in most brain regions under investigation. In conclusion, aluminum and fluoride are very noxious environmental pollutants that interfere with the proper functions of the brain neurons and their combination together aggravates their hazard.


Substance Use Disorder Training Workshop for Future Interprofessional Health Care Providers.
Rates of substance use disorders, including opioid misuse, continue to rise despite national initiatives. Because of this, health professional schools from Rhode Island joined together to design and implement a single-day interprofessional education workshop on substance use disorder training. This workshop consists of four sessions. The first is a patient panel featuring both patients recovering from substance use disorders and their health care providers. Next is a naloxone administration training session. This is followed by a standardized patient session featuring an individual who requires nonopioid options for chronic pain treatment and in which health professional students work together to take a history, perform a physical examination, and develop a treatment plan. Finally, the last session is a complex paper-based case study focusing on a homeless individual with diverse medical problems requiring multifaceted care. A total of 540 students from a variety of health care professions participated in the workshop. Students were asked to evaluate each component of the workshop, as well as the workshop overall, on a 6-point Likert scale (1 = poor, 6 = outstanding). Students rated the overall workshop at 76% (4.54 out of 6), and the sessions received ratings ranging from 67% (4.01 out of 6 for the case study) to 83% (4.96 out of 6 for the patient/provider panel). This curriculum can be adapted and implemented at other medical schools to provide opportunities for future health care professionals to learn how to work effectively in interprofessional teams to manage substance use disorders.


Integral equation formulation for reflection by a mirror.
When light is incident on a mirror, it induces a current density on its surface. This surface current density emits radiation, which is the observed reflected field. We consider a monochromatic incident field with an arbitrary spatial dependence, and we derive an integral equation for the Fourier-transformed surface current density. This equation contains the incident electric field at the surface as an inhomogeneous term. The incident field, emitted by a source current density in front of the mirror, is then represented by an angular spectrum, and this leads to a solution of the integral equation. From this result we derive a relation between the surface current density and the current density of the source. It is shown with examples that this approach provides a simple method for obtaining the surface current density. It is also shown that with the solution of the integral equation, an image source can be constructed for any current source, and as illustration we construct the images of electric and magnetic dipoles and the mirror image of an electric quadrupole. By applying the general solution for the surface current density, we derive an expression for the reflected field as an integral over the source current distribution, and this may serve as an alternative to the method of images.


Gastric cancer: French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO).
This document is a summary of the French Intergroup guidelines regarding the management of gastric cancer published in October 2016, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org), updated in October 2017. This collaborative work was realized under the auspices of several French medical societies involved in management of gastric cancer. Recommendations are graded in three categories (A-C), according to the amount of evidence found in the literature until July 2017. There are several known risk factors for gastric cancer, including Helicobacter pylori and genetic predispositions, both requiring a specific screening for patients and their relatives. The diagnosis and staging evaluation are essentially based on gastroscopy plus biopsies and computed tomography scan. The endoscopic ultrasonography can be used for superficial tumors in case of discussion for endoscopic resection (T1N0). For local disease (N+ and/or T > T1), the strategic therapy is based on surgery associated with perioperative chemotherapy. In the absence of preoperative treatment (for any raison), the postoperative chemoradiotherapy (or chemotherapy) should be discussed for patients with stage II or III tumor. For metastatic disease, the treatment is based on "palliative" chemotherapy consisting in a doublet or triplet regimens depending of age, performance status and HER2 tumor status. For patients with limited metastatic disease, surgical resection could be discussed in multidisciplinary meeting in case of stable disease after chemotherapy. These guidelines in gastric cancer are done to help decision for daily clinical practice. These recommendations are permanently being reviewed. Each individual case must be discussed within a multidisciplinary team.


Influencing Factors of High-Risk Human Papillomavirus Infection and DNA Load According to the Severity of Cervical Lesions in Female Coal Mine Workers of China.
High-risk human papillomavirus (HR-HPV) plays an aetiological role in the progression of cervical cancer and precancerous lesions. Determining the risk factors of HR-HPV infection is useful for HR-HPV infection surveillance and control. We aimed to explore the influencing factors of HR-HPV infection in female coal mine workers, and to evaluate the associations between HR-HPV DNA load and cytological and histological changes of cervix. In total 6,325 participants completed standard questionnaire on potential influencing factors of HR-HPV infection and underwent gynecological examinations, HPV test as well as Thinprep cytology test (TCT). 1,512 women with positive results of HPV and/or TCT were referred to colposcopy with biopsy and histological examination. HR-HPV DNA load was evaluated by Digene second generation hybrid capture (HC2) assay. Multiple unconditional logistic regression analysis was used to determine the influencing factors for HR-HPV infection. Of 6,325 study participants, 1,405 (22.2%) were HR-HPV positive. HR-HPV infection rate was higher in women aged 30-50 years, with lower education level, working inside the mines and engaging in shift work. Risk factors for HR-HPV infection in female coal mine workers included contraception (OR=1.395, 95%CI=1.102-1.458), previous artificial abortion (OR=1.603, 95%CI=1.202-1.856), working inside the mines (OR=1.230, 95%CI=1.056-1.528) and history of gynecological diseases (OR=1.198, 95%CI=1.001-1.462), while menopause was a protective factor (OR=0.402, 95%CI=0.306-0.507). The HR-HPV DNA load significantly increased with the severity of cervical cytological (χ 2 trend=177.372, p<0.001) and histological (χ 2 trend=194.501, p<0.001) changes. The results indicated that HR-HPV infection is highly prevalent in female coal mine workers in China. Contraception, artificial abortion, working inside the mines and gynecological diseases could increase the risk of HR-HPV infection in these women. HR-HPV DNA load might predict risks of cervical precancerous lesions and cancer. Our findings could provide scientific basis for reducing the risk of HR-HPV infection and cervical cancer in this vulnerable population.