Electromagnetic therapy for treating venous leg ulcers.
Leg ulceration is a common, chronic, recurring condition. The estimated prevalence of leg ulcers in the UK population is 1.5 to 3 per 1000. Venous ulcers (also called stasis or varicose ulcers) comprise 80% to 85% of all leg ulcers. Electromagnetic therapy (EMT) is sometimes used as a treatment to assist the healing of chronic wounds such as venous leg ulcers. To assess the effects of EMT on the healing of venous leg ulcers. For this fourth update, we searched The Cochrane Wounds Group Specialised Register (searched 30 January 2015); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 12). Randomised controlled trials comparing EMT with sham-EMT or other treatments. Standard Cochrane Collaboration methods were employed. At least two review authors independently scrutinised search results and obtained full reports of potentially eligible studies for further assessment. We extracted and summarised details of eligible studies using a data extraction sheet, and made attempts to obtain missing data by contacting study authors. A second review author checked data extraction, and we resolved disagreements after discussion between review authors. Three randomised controlled trials (RCTs) of low or unclear risk of bias, involving 94 people, were included in the original review; subsequent updates have identified no new trials. All the trials compared the use of EMT with sham-EMT. Meta-analysis of these trials was not possible due to heterogeneity. In the two trials that reported healing rates; one small trial (44 participants) reported that significantly more ulcers healed in the EMT group than the sham-EMT group however this result was not robust to different assumptions about the outcomes of participants who were lost to follow up. The second trial that reported numbers of ulcers healed found no significant difference in healing. The third trial was also small (31 participants) and reported significantly greater reductions in ulcer size in the EMT group however this result may have been influenced by differences in the prognostic profiles of the treatment groups. It is not clear whether electromagnetic therapy influences the rate of healing of venous leg ulcers. Further research would be needed to answer this question.


Effects of soil lead exposure and land use characteristics on neurodevelopment among children under 3 years of age in northern Taiwan.
Lead (Pb) exposure increases the risks of neurodevelopmental disorders in children. Child-specific activities and land use scenarios may lead to elevated opportunities for Pb exposure through the soil. Therefore, we investigated hair and fingernail Pb concentrations among young children in northern Taiwan, in relation to soil Pb pollution and land use characteristics. We also explored the effect of the Pb exposure burden and land use scenarios on neurobehavioral development. In total, 139 healthy children under 3 years of age were recruited in October 2011 to April 2014. Pb levels in hair and fingernail samples were determined using an inductively coupled plasma/mass spectrometer. Pb concentrations in soils and land use types surrounding the children's homes were accessed by a geographic information system to identify any associations with hair Pb levels. The Bayley Scales of Infant and Toddler Development (Bayley-III) were used to evaluate the cognitive, language, and motor development of the children. A multivariable regression model was performed to assess the effects of soil Pb levels and land-use status on Pb exposure in children, as well as associations of Pb exposure and land-use scenarios with neurodevelopmental abilities. Geometric mean Pb concentrations in hair, fingernails, and soil were 2.9 ± 4.8 μg/g, 0.8 ± 5.1 μg/g, and 20.8 ± 4.3 mg/kg, respectively. The multivariable analysis indicated that soil Pb concentrations and green areas around residences had potential links with Pb exposure among children in northern Taiwan. Hair Pb concentrations were negatively associated with expressive language scores. Soil Pb exposure was positively associated with hair Pb concentrations. Land use types around the children's homes in northern Taiwan were associated with their neurodevelopment. Increased green areas were negatively associated with hair Pb concentrations. Living near a highway may have had negative impacts on gross motor scores. A healthy residence can avoid potential health risks for children during their early life.


Proportional Insulin Infusion in Closed-Loop Control of Blood Glucose.
A differential equation model is formulated that describes the dynamics of glucose concentration in blood circulation. The model accounts for the intake of food, expenditure of calories and the control of glucose levels by insulin and glucagon. These and other hormones affect the blood glucose level in various ways. In this study only main effects are taken into consideration. Moreover, by making a quasi-steady state approximation the model is reduced to a single nonlinear differential equation of which parameters are fit to data from healthy subjects. Feedback provided by insulin plays a key role in the control of the blood glucose level. Reduced β-cell function and insulin resistance may hamper this process. With the present model it is shown how by closed-loop control these defects, in an organic way, can be compensated with continuous infusion of exogenous insulin.


Affinity proteomics discovers decreased levels of AMFR in plasma from Osteoporosis patients.
Affinity proteomic approaches by antibody bead arrays enable multiplexed analysis of proteins in body fluids. In the presented study, we investigated blood plasma within osteoporosis to discovery differential protein profiles and to propose novel biomarkers candidates for subsequent studies. Starting with 4608 antibodies and plasma samples from 22 women for an untargeted screening, a set of 72 proteins were suggested for further analysis. Complementing these with targets from literature and other studies, a targeted bead array of 180 antibodies was built to profile for 92 proteins in plasma samples of 180 women from two independent population-based studies. Differential profiles between osteoporosis patients and matched controls were discovered for 12 proteins in at least one of the two study sets. Among these targets, the levels of autocrine motility factor receptor (AMFR) were concordantly lower in plasma of female osteoporosis patients. Subsequently, verification of anti-AMFR antibody selectivity was conducted using high-density peptide and protein arrays, and Western blotting. Further validation in additional study sets will be needed to determine the clinical value of the observed decrease in AMFR plasma levels in osteoporosis patients, but AMFR may aid our understanding of disease mechanisms and could support existing tools for diagnosis and monitoring of patient mobility within osteoporosis.


Basal contralateral aldosterone suppression is rare in lateralized primary aldosteronism.
Unilateral aldosteronomas should suppress renin and contralateral aldosterone secretion. Complete aldosterone suppression in contralateral adrenal vein sample (AVS) could predict surgical outcomes. To retrospectively evaluate the prevalence of basal contralateral suppression using Aldosterone (A)contralateral(CL)/Aperipheral(P) as compared to (A/Cortisol(C)CL)/(A/C)P ratio in primary aldosteronism (PA) patients studied in two Canadian centers. To determine the best cut-off to predict clinical and biochemical surgical cure. To compare the accuracy of ACL/AP to the basal and post-ACTH lateralization index (LI) in predicting surgical cure. In total, 330 patients with PA and successful AVS were included; 124 lateralizing patients underwent surgery. Clinical and biochemical cure at 3 and 12 months were evaluated using the PASO criteria. Using ACL/AP and (A/C)CL/(A/C)P at the cut-off of 1, the prevalence of contralateral suppression was 6 and 45%, respectively. Using ROC curves, the ACL/AP ratio is associated with clinical cure at 3 and 12 months and biochemical cure at 12 months. (A/C)CL/(A/C)P is associated with biochemical cure only. The cut-offs for ACL/AP offering the best sensitivity (Se) and specificity (Sp) for clinical and biochemical cures at 12 months are 2.15 (Se: 63% and Sp: 71%) and 6.15 (Se: 84% and Sp: 77%), respectively. Basal LI and post-ACTH LI are associated with clinical cure but only the post-ACTH LI is associated with biochemical cure. In lateralized PA, basal contralateral suppression defined by ACL/AP is rare and incomplete compared to the (A/C)CL/(A/C)P ratio and is associated with clinical and biochemical postoperative outcome, but with modest accuracy.


Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts.
High-grade serous carcinoma has a poor prognosis, owing primarily to its early dissemination throughout the abdominal cavity. Genomic and proteomic approaches have provided snapshots of the proteogenomics of ovarian cancer1,2, but a systematic examination of both the tumour and stromal compartments is critical in understanding ovarian cancer metastasis. Here we develop a label-free proteomic workflow to analyse as few as 5,000 formalin-fixed, paraffin-embedded cells microdissected from each compartment. The tumour proteome was stable during progression from in situ lesions to metastatic disease; however, the metastasis-associated stroma was characterized by a highly conserved proteomic signature, prominently including the methyltransferase nicotinamide N-methyltransferase (NNMT) and several of the proteins that it regulates. Stromal NNMT expression was necessary and sufficient for functional aspects of the cancer-associated fibroblast (CAF) phenotype, including the expression of CAF markers and the secretion of cytokines and oncogenic extracellular matrix. Stromal NNMT expression supported ovarian cancer migration, proliferation and in vivo growth and metastasis. Expression of NNMT in CAFs led to depletion of S-adenosyl methionine and reduction in histone methylation associated with widespread gene expression changes in the tumour stroma. This work supports the use of ultra-low-input proteomics to identify candidate drivers of disease phenotypes. NNMT is a central, metabolic regulator of CAF differentiation and cancer progression in the stroma that may be therapeutically targeted.


Elastofibroma: MR and CT appearance with radiologic-pathologic correlation.
The purpose of our study was to determine the MR and CT appearances of elastofibroma and correlate the imaging features with the underlying pathologic findings. We reviewed retrospectively the MR and CT findings in five cases of elastofibroma. All patients had a soft-tissue mass; one patient also complained of pain. The mean age of the patients was 71 years (range, 63-79 years). Four lesions occurred in the subscapular region, and one occurred in the thigh. In addition, we reviewed and compared the demographic data of 72 histologically proved cases for which we had archival data. Three of four lesions evaluated with spin-echo MR imaging were approximately isointense with skeletal muscle and contained areas with a signal intensity similar to that of fat; these corresponded to areas of dense collagen and interspersed fat, respectively. In the fourth case, the MR appearance was nonspecific. In one case, MR imaging with gadopentetate dimeglumine showed areas with and without enhancement. Three of four lesions evaluated with CT had variable margins, with tissue attenuation similar to that of the adjacent soft tissue as well as scattered areas of decreased attenuation, suggesting fat within the lesion. In one case, the lesion was well defined and relatively homogeneous with an attenuation less than that of skeletal muscle. The MR and CT features of elastofibroma are different from those of most other soft-tissue tumors, reflecting entrapped fat within a predominantly fibrous mass. Although these features are not pathognomonic, their presence in a subscapular lesion in an older patient suggests a presumptive diagnosis of elastofibroma.


Selenium elimination in pigs after an outbreak of selenium toxicosis.
In May 1996, 150 grower pigs in 5 California counties were exposed to selenium-contaminated feed distributed by a single feed company. Feed samples from 20 herds had a mean selenium concentration of 121.7 ppm dry weight (range, 22.1-531 ppm). In San Luis Obispo County, 52 pigs in 24 herds were exposed to the feed, and 8 pigs died with signs of paralysis. Bilateral symmetrical poliomyelomalacia involving the ventral horns of the cervical and lumbar intumescence was evident on histologic examination of spinal cord from affected pigs. Of 44 surviving exposed pigs, 33 (75%) exhibited signs of selenosis, including anorexia, alopecia, and hoof lesions. Thirty-nine of 44 pigs (88.6%) had elevated (>1 ppm) blood selenium concentrations. Surviving exposed pigs were changed to a standard commercial ration containing approximately 0.5 ppm (dry weight) selenium. Blood selenium concentrations were determined weekly for 46 days following removal of the contaminated feed and were compared with values of 20 control pigs fed a standard commercial ration. Mean (+/-SD) blood selenium concentrations of exposed pigs were 3.2 +/- 2.6 ppm at the initial sampling and 0.4 +/- 0.1 ppm after 46 days. Mean blood selenium concentrations of < or = 0.3 ppm for control pigs at all samplings were significantly lower (P < 0.001) than concentrations for exposed pigs. Muscle and liver samples of 22 of the 44 exposed pigs were collected at slaughter approximately 72 days after withdrawal of the selenium-contaminated feed. Muscle samples had a mean selenium concentration of 0.36 ppm (wet weight). Liver samples had a mean selenium concentration of 1.26 ppm (wet weight). One liver sample had a selenium value in the toxic range for pigs (3.3 ppm wet weight; reference range, 0.4-1.2 ppm). A 1-compartment pharmacokinetic model of selenium elimination in exposed pigs was generated, and the geometric mean blood selenium elimination half-life was estimated to be 12 days. The 60-day withdrawal time recommended by the Food Animal Residue Avoidance Database was considered sufficient to allow safe human consumption of tissues from exposed pigs.


[Comparison of the effectiveness of acupuncture and physical therapy in ambulatory patients with gonarthrosis].
A comparative study between acupuncture and physical therapy in patients with gonarthrosis is reported. Patients treated with physical therapy showed 4 parameters significantly reduced after a treatment duration of 2 weeks, and 7 out of 10 parameters after 4 weeks of therapy. Acupuncture could better 2 parameters but only after 4 weeks of treatment. Although physical therapy was superior in most of the objective measurements, the subjective judgement by the patients of the efficacy of both treatments found no significant difference. In summary acupuncture is thought to be only an additional form of treatment in gonarthrosis.


NRAS, FLT3 and TP53 mutations in patients with myelodysplastic syndrome and a del(5q).
Mutations of the NRAS and TP53 genes and internal tandem duplication (ITD) of the FLT3 gene are among the most frequently observed molecular abnormalities in the myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We sought to determine the incidence of these abnormalities in patients with MDS and a 5q deletion. NRAS and FLT3 mutations are uncommon in MDS patients with a 5q deletion and TP53 mutation is associated with the more advanced MDS subtypes.


Integrating biodegradation and electroosmosis for the enhanced removal of polycyclic aromatic hydrocarbons from creosote-polluted soils.
This paper presents a hybrid technology of soil remediation based on the integration of biodegradation and electroosmosis. We employed soils with different texture (clay soil and loamy sand) containing a mixture of polycyclic aromatic hydrocarbons (PAH) present in creosote, and inoculation with a representative soil bacterium able to degrade fluorene, phenanthrene, fluoranthene, pyrene, anthracene, and benzo[a]pyrene. Two different modes of treatment were prospected: (i) inducing in soil the simultaneous occurrence of biodegradation and electroosmosis in the presence of a biodegradable surfactant, and (ii) treating the soils sequentially with electrokinetics and bioremediation. Losses of PAH due to simultaneous biodegradation and electroosmosis (induced by a continuous electric field) were significantly higher than in control cells that contained the surfactant but no biological activity or no current. The method was especially successful with loamy sand. For example, benzo[a]pyrene decreased its concentration by 50% after 7 d, whereas 22 and 17% of the compound had disappeared as a result of electrokinetic flushing and bioremediation alone, respectively. The use of periodical changes in polarity and current pulses increased by 16% in the removal of total PAH and in up to 30% of specific compounds, including benzo[a]pyrene. With the aim of reaching lower residual levels through bioremediation, an electrokinetic pretreatment was also evaluated as a way to mobilize the less bioaccessible fraction of PAH. Residual concentrations of total biodegradable PAH, remaining after bioremediation in soil slurries, were twofold lower in electrokinetically pretreated soils than in untreated soils. The results indicate that biodegradation and electroosmosis can be successfully integrated to promote the removal of PAH from soil.


History and evolution of alpine plants endemic to the Qinghai-Tibetan Plateau: Aconitum gymnandrum (Ranunculaceae).
How Quaternary climatic oscillations affected range distributions and intraspecific divergence of alpine plants on the Qinghai-Tibetan Plateau (QTP) remains largely unknown. Here, we report a survey of chloroplast DNA (cpDNA) and nuclear ribosomal internal transcribed spacer (ITS) DNA variation aimed at exploring the phylogeographical history of the QTP alpine endemic Aconitum gymnandrum. We sequenced three cpDNA fragments (rpl20-rps12 intergenic spacer, the trnV intron and psbA-trnH spacer) and also the nuclear (ITS) region in 245 individuals from 23 populations sampled throughout the species' range. Two distinct lineages, with eastern and western geographical distributions respectively, were identified from a phylogenetic analysis of ITS sequence variation. Based on a fast substitution rate, these were estimated to have diverged from each other in the early Pleistocene approximately 1.45 Ma. The analysis of cpDNA variation identified nine chlorotypes that clustered into two major clades that were broadly congruent in geographical distribution with the two ITS lineages. The east-west split of cpDNA divergence was supported by an amova which partitioned approximately half of the total variance between these two groups of populations. Analysis of the spatial distribution of chlorotypes showed that each clade was subdivided into two groups of populations such that a total of four population groups existed in the species. It is suggested that these different groups derive from four independent glacial refugia that existed during the Last Glacial Maximum (LGM), and that three of these refugia were located at high altitude on the QTP platform itself at that time. Coalescent simulation of chlorotype genealogies supported both an early Pleistocene origin of the two main cpDNA clades and also the 'four-refugia' hypothesis during the LGM. Two previous phylogeographical studies of QTP alpine plants indicated that such plants retreated to refugia at the eastern/south-eastern plateau edge during the LGM and/or previous glacial maxima. However, the results for A. gymnandrum suggest that at least some of these cold-tolerant species may have also survived centrally on the QTP platform throughout the Quaternary.


Safety and efficacy of instrumented convex growth arrest in treatment of congenital scoliosis.
Anterior and posterior convex hemiepiphysiodesis is a widely used surgical alternative in the treatment of congenital scoliosis. This procedure has the disadvantage of the need for both anterior and posterior approaches. Furthermore, outcomes may be unpredictable. Posterior convex growth arrest (CGA) with pedicle screws at each segment on the convex side may obviate the need for anterior surgery and provides more predictable outcomes. This study retrospectively evaluates the safety and efficacy of instrumented posterior CGA in congenital scoliosis. Patients who had posterior CGA with convex pedicle screw instrumentation for congenital scoliosis were evaluated retrospectively. Thirteen patients (6 male, 7 female) were included in the study. Preoperative, early postoperative, and last follow-up standing posteroanterior and lateral x-rays were evaluated. Cobb angles were recorded for the instrumented segment (main curve). Global thoracic kyphosis was measured between T2 and T12 on sagittal plane. These values were compared preoperatively, postoperatively, and at last follow-up. The T1-S1 vertical height and the height between the concave side pedicles of the upper and lower end vertebra of the main curve was also determined and recorded as the concave height. The average follow-up was 56.1±10 months (range, 36 to 74 mo) and the average age of the patients at the time of operation was 64.5±30.1 months (range, 15 to 108 mo). All patients were Risser zero at the time of surgery. The average curve magnitude was 49±10.9 degrees (range, 34 to 68 degrees) preoperatively, 38.3±9.7 degrees (range, 28 to 58 degrees) early postoperatively, and 33.5±12.4 degrees (16 to 52 degrees) at last follow-up. There was a significant difference between the preoperative and early postoperative main curve Cobb angle measurements (P=0.001). The average concave height was 94.2±20.2 mm in the early postoperative period and 104.7±21.7 mm at last follow-up (P=0.003). The average T1-S1 height was 292.1±67.1 mm in the early postoperative period and 363.9±94.5 mm at last follow-up (P=0.005). There was at least ≥5 degrees improvement in 9 of the 12 patients in the follow-up period after the index procedure. In 3 patients, the curve did not change and the correction was maintained. Curve progression was observed in 1 patient due to a technical error. There were no wound infections or instrumentation failures during follow-up. Instrumented CGA can safely be used in long sweeping curves of immature spines. Using this technique; thoracotomy, anterior procedure, and 2-stage surgery can be avoided. Moreover, it guarantees some degree of correction in all patients because of the instrumentation effect, eliminating the unpredictable nature of classic CGA. Therapeutic level IV study.


Pediatric rhinoplasty in an academic setting.
Nasal septal surgery and rhinoplasty are controversial in children. Traditionally, an attitude of restraint has been employed by most surgeons till an empirical age of 16 to 18 years. This is to avoid the possible adverse effects that the growth spurts may have on the nose and midface region. Some authors, however, have claimed a paucity of evidence that such untoward effects of surgery are frequent. Research has shown that surgical intervention limited to certain areas of the bony and cartilaginous nasal framework is less likely to affect natural growth patterns. There is a growing consensus toward early intervention, especially in a select group of patients, where deferring the surgery may turn out to be the poorer option in the short and the long term, and suggestions have been made that conservative guidelines may be employed to minimize the unwarranted results. This article presents our experience with septorhinoplasty in children over the last two decades in an academic setting. We have retrospectively studied the pediatric patients who underwent septorhinoplasty at the Academic Medical Centre, Amsterdam, Netherlands. There were 106 children aged between 3 and 19 years who underwent nasal surgery between February 1994 and August of 2007. Sixty-six of these were boys and 40 were girls. Their follow-up ranged from 12 to 157 months with a mean follow-up period of 53 months. Eighteen patients underwent revision surgery. The clinical circumstances, indications for surgery, extent of surgical interference, and outcome in 106 patients are discussed. Importantly, the patients in this series have been followed for variable periods after puberty and adolescence, allowing for assessment beyond the nasal and midfacial growth spurts. Based on our experience, we have outlined the clinical guidelines that we follow for surgery in this age group of patients.


Differential temporal profile of lowered blood glucose levels (3.5 to 6.5 mmol/l versus 5 to 8 mmol/l) in patients with severe traumatic brain injury.
Hyperglycaemia is detrimental, but maintaining low blood glucose levels within tight limits is controversial in patients with severe traumatic brain injury, because decreased blood glucose levels can induce and aggravate underlying brain injury. In 228 propensity matched patients (age, sex and injury severity) treated in our intensive care unit (ICU) from 2000 to 2004, we retrospectively evaluated the influence of different predefined blood glucose targets (3.5 to 6.5 versus 5 to 8 mmol/l) on frequency of hypoglycaemic and hyperglycaemic episodes, insulin and norepinephrine requirement, changes in intracranial pressure and cerebral perfusion pressure, mortality and length of stay on the ICU. Mortality and length of ICU stay were similar in both blood glucose target groups. Blood glucose values below and above the predefined levels were significantly increased in the 3.5 to 6.5 mmol/l group, predominantly during the first week. Insulin and norepinephrine requirements were markedly increased in this group. During the second week, the incidences of intracranial pressure exceeding 20 mmHg and infectious complications were significantly decreased in the 3.5 to 6.5 mmol/l group. Maintaining blood glucose within 5 to 8 mmol/l appears to yield greater benefit during the first week. During the second week, 3.5 to 6.5 mmol/l is associated with beneficial effects in terms of reduced intracranial hypertension and decreased rate of pneumonia, bacteraemia and urinary tract infections. It remains to be determined whether patients might profit from temporally adapted blood glucose limits, inducing lower values during the second week, and whether concomitant glucose infusion to prevent hypoglycaemia is safe in patients with post-traumatic oedema.


The mental foramen and nerve: clinical and anatomical factors related to dental implant placement: a literature review.
The mental foramen is a strategically important landmark during osteotomy procedures. Its location and the possibility that an anterior loop of the mental nerve may be present mesial to the mental foramen needs to be considered before implant surgery to avoid mental nerve injury. Articles that addressed the position, number, and size of the mental foramen, mental nerve anatomy, and consequences of nerve damage were evaluated for information pertinent to clinicians performing implant dentistry. The mental foramen may be oval or round and is usually located apical to the second mandibular premolar or between apices of the premolars. However, its location can vary from the mandibular canine to the first molar. The foramen may not appear on conventional radiographs, and linear measurements need to be adjusted to account for radiographic distortion. Computerized tomography (CT) scans are more accurate for detecting the mental foramen than conventional radiographs. There are discrepancies between studies regarding the prevalence and length of the loop of the mental nerve mesial to the mental foramen. Furthermore, investigations that compared radiographic and cadaveric dissection data with respect to identifying the anterior loop reported that radiographic assessments result in a high percentage of false-positive and -negatives findings. Sensory dysfunction due to nerve damage in the foraminal area can occur if the inferior alveolar or mental nerve is damaged during preparation of an osteotomy. To avoid nerve injury during surgery in the foraminal area, guidelines were developed based on the literature with respect to verifying the position of the mental foramen and validating the presence of an anterior loop of the mental nerve. These guidelines included leaving a 2 mm zone of safety between an implant and the coronal aspect of the nerve; observation of the inferior alveolar nerve and mental foramen on panoramic and periapical films prior to implant placement; use of CT scans when these techniques do not provide clarity with respect to the position of the nerve; surgical corroboration of the mental foramen's position when an anterior loop of the mental foramen is suspected of being present or if it is unclear how much bone is present coronal to the foramen to establish a zone of safety (in millimeters) for implant placement; once a safety zone is identified, implants can be placed anterior to, posterior to, or above the mental foramen; and prior to placing an implant anterior to the mental foramen that is deeper than the safety zone, the foramen must be probed to exclude the possibility that an anterior loop is present. In general, altered lip sensations are preventable if the mental foramen is located and this knowledge is employed when performing surgical procedures in the foraminal area.


Acoustic bubble dynamics in a yield-stress fluid.
Yield-stress fluids naturally trap small bubbles when their buoyancy applies an insufficient stress to induce local yielding of the material. Under acoustic excitation, trapped bubbles can be driven into volumetric oscillations and apply an additional local strain and stress that can trigger yielding and assist their release. In this paper we explore different regimes of microbubble oscillation and translation driven by an ultrasound field in a model yield-stress fluid, a Carbopol microgel. We first analyse the linear bubble oscillation dynamics to measure the local, high-frequency viscosity of the material. We then use acoustic pressure gradients to induce bubble translation and examine the elastic part of the response of the material below yielding. We find that, at moderate pressure amplitude, the additional stresses applied by volumetric oscillations and acoustic radiation forces do not lead to any detectable irreversible bubble motion. At high pressure amplitude, we observe non-spherical shape oscillations that result in erratic bubble motion. The critical pressures we observe differ from the predictions of a recent model of shape oscillations in soft solids. Based on our findings, we discuss possible reasons for the lack of bubble release in Carbopol and suggest other systems in which ultrasound-assisted bubble rise may be observed.


Exogenous Cripto-1 Suppresses Self-Renewal of Cancer Stem Cell Model.
Cripto-1 is a glycophosphatidylinositol (GPI) anchored signaling protein of epidermal growth factor (EGF)-Cripto-1-FRL1-Cryptic (CFC) family and plays a significant role in the early developmental stages and in the different types of cancer cells, epithelial to mesenchymal transition and tumor angiogenesis. Previously, we have developed cancer stem cells (miPS-LLCcm) from mouse iPSCs by culturing them in the presence of conditioned medium of Lewis Lung Carcinoma (LLC) cells for four weeks. Nodal and Cripto-1 were confirmed to be expressed in miPS-LLCcm cells by quantitative reverse transcription PCR (rt-qPCR) implying that Cr-1 was required in maintaining stemness. To investigate the biological effect of adding exogenous soluble CR-1 to the cancer stem cells, we have prepared a C-terminally truncated soluble form of recombinant human CR-1 protein (rhsfCR-1), in which the GPI anchored moiety was removed by substitution of a stop codon through site-directed mutagenesis. rhsfCR-1 effectively suppressed the proliferation and sphere forming ability of miPS-LLCcm cells in a dose-dependent manner in the range of 0 to 5 µg/mL, due to the suppression of Nodal-Cripto-1/ALK4/Smad2 signaling pathway. Frequency of sphere-forming cells was dropped from 1/40 to 1/69 by rhsfCR-1 at 1 µg/mL. Moreover, rhsfCR-1 in the range of 0 to 1 µg/mL also limited the differentiation of miPS-LLCcm cells into vascular endothelial cells probably due to the suppression of self-renewal, which should reduce the number of cells with stemness property. As demonstrated by a soluble form of exogenous Cripto-1 in this study, the efficient blockade would be an attractive way to study Cripto-1 dependent cancer stem cell properties for therapeutic application.


Acute effects of different multivitamin mineral preparations with and without Guaraná on mood, cognitive performance and functional brain activation.
Previous work has identified the positive effects of the acute administration of a multivitamin-guaraná preparation during an effortful executive/working memory task. Here, we aimed to differentiate the effects of multivitamins with and without guaraná and to examine the neural substrates of such effects using functional magnetic resonance imaging (fMRI). Following a double-blind, placebo-controlled, randomised, balanced crossover design, 20 participants (mean age 29 ± 5.54 years) consumed multivitamin preparations with or without guaraná (Berocca® Performance and Boost, respectively) and a placebo. Thirty minutes post-treatment, they underwent neurocognitive assessment, consisting of a 10 min Cognitive Demand Battery, with mood ratings taken immediately before and after the battery. Five additional participants underwent post-treatment fMRI scanning during Rapid Visual Information Processing and Inspection Time activation tasks. The multivitamin with guaraná treatment was associated with significantly enhanced Serial Threes performance and self-rated contentment. fMRI revealed that both multivitamin treatments increased activation in areas associated with working memory and attentional processing, with the effect being greater in the multivitamin with guaraná condition. These data confirm the acute benefits of multivitamins with guaraná on mood and cognitive performance. Furthermore, they demonstrate for the first time increased brain activation from multivitamin preparations both with and without guaraná, as measured using fMRI.


Cyclosporin A inhibits initiation but not progression of human T cell proliferation triggered by phorbol esters and calcium ionophores.
Cyclosporin A (CsA) is a potent inhibitor of T lymphocyte proliferation induced by Ag and mitogens. In an attempt to further delineate the mechanism of action of CsA, we have examined its effects on T cell proliferation induced by the combination of the phorbol ester, phorbol 12,13-dibutyrate (PDB), and the calcium ionophore, ionomycin. T cells were rendered competent as the result of a 30-min initial incubation with both drugs, after which the drugs were washed out. Competence is defined as the ability to subsequently proliferate in response to exogenously added IL-2 or PDB in the second phase of the culture, but not to synthesize IL-2 or proliferate without these additions. Addition of CsA (1 microgram/ml) to the cells in the initial, competence-inducing 30-min incubation with PDB/ionomycin abrogated their subsequent response to IL-2 or PDB. In contrast, addition of CsA to cells after they had been treated for 30 min with PDB/ionomycin and then washed did not affect their responses to subsequent addition of either IL-2 or PDB. Treatment with CsA during induction of competence prevented the expression of the 55-kDa IL-2R gene during competence induction and inhibited IL-2 gene expression and IL-2 production in response to PDB in the second phase. These results indicate that the effects of CsA are limited to the initiation (competence induction) period of T cell activation, that CsA apparently affects expression of more than one gene, and in competent cells, CsA does not affect their ability to progress to DNA synthesis.


Relationship between abdominal trauma or surgery and mesenteric panniculitis.
Mesenteric panniculitis is a rare disease characterized by chronic non-specific inflammation of mesenteric fat tissue. Several etiologic and/or associated factors have been reported in the literature so far. Although trauma or surgery is one of the potential etiologic factors for mesenteric panniculitis, to the best of our knowledge, no strong correlation has been shown in the literature until now.


Findings from an assessment of state Title V workforce development needs.
To describe results of a 2008 assessment of Title V workforce competencies and training needs at the state level, and examine preferences and barriers related to available education and training opportunities. A web-based survey was administered May through August, 2008 to Maternal and Child Health (MCH) and Children and Youth with Special Health Care Needs (CYSHCN) program leaders in all 50 states, and U.S. jurisdictions. Forty-nine MCH (96%) and 44 CYSHCN (86%) programs and four territories completed surveys. A major focus of the survey related to competencies in six core domains: Public Health/Title V Knowledge Base, Communication, Critical Thinking, Management Skills, Family Centered Care and Medical Home, and Leadership Development. The top training needs identified by state Title V programs fall into the global category of critical thinking, including skills in MCH data synthesis and translation, in program evaluation, and in systems thinking. The need to enhance personal rather than organizational leadership skills was emphasized. Blended learning approaches (graduate education), and national conferences with skills building workshops (continuing education) were identified as preferred training modalities. Barriers to training included lack of career opportunities, insufficient agency support, and inability to take leave (graduate education), and travel restrictions, release time limitations, costs, and limited geographic access (continuing education). Both the focus of training and preferred training modalities differed from previous MCH workforce survey findings. Given the changing needs expressed by state Title V leaders as well as their training preferences, it is important that current and future graduate education and continuing education approaches be better aligned to meet these needs and preferences.


Engaging patients and caregivers in prioritizing symptoms impacting quality of life for Duchenne and Becker muscular dystrophy.
Patient preference information (PPI) have an increasing role in regulatory decision-making, especially in benefit-risk assessment. PPI can also facilitate prioritization of symptoms to treat and inform meaningful selection of clinical trial endpoints. We engaged patients and caregivers to prioritize symptoms of Duchenne and Becker muscular dystrophy (DBMD) and explored preference heterogeneity. Best-worst scaling (object case) was used to assess priorities across 11 symptoms of DBMD that impact quality of life and for which there is unmet need. Respondents selected the most and least important symptoms to treat among a subset of five. Relative importance scores were estimated for each symptom, and preference heterogeneity was identified using mixed logit and latent class analysis. Respondents included patients (n = 59) and caregivers (n = 96) affected by DBMD. Results indicated that respondents prioritized "weaker heart pumping" [score = 5.13; 95% CI (4.67, 5.59)] and pulmonary symptoms: "lung infections" [3.15; (2.80, 3.50)] and "weaker ability to cough" [2.65; (2.33, 2.97)] as the most important symptoms to treat and "poor attention span" as the least important symptom to treat [- 5.23; (- 5.93, - 4.54)]. Statistically significant preference heterogeneity existed (p value < 0.001). At least two classes existed with different priorities. Priorities of the majority latent class (80%) reflected the aggregate results, whereas the minority latent class (20%) did not distinguish among pulmonary and other symptoms. Estimates of the relative importance for symptoms of Duchenne muscular dystrophy indicated that symptoms with direct links to morbidity and mortality were prioritized above other non-skeletal muscle symptoms. Findings suggested the existence of preference heterogeneity for symptoms, which may be related to symptom experience.


Claiming comprehensive sex education is a right does not make it so: a close reading of international law.
The international community is currently debating whether international law requires States to educate adolescents about their sexuality. Various nongovernmental organizations, United Nations Special Rapporteurs, and treaty-monitoring bodies assert a right to comprehensive sex education, a controversial approach to sex education that arguably encourages adolescents to experiment with their sexuality. This assertion of a right to comprehensive sex education is erroneous and misleading. International human rights are created in two ways: by treaty and by custom. Treaties do not mention comprehensive sex education, or any other form of sex education or training. Custom, found in international consensus documents and other declarations of political will, and confirmed by State practice, holds no universal agreement on sex education. Because neither treaty nor custom creates a right to comprehensive sex education, no such right exists.


Estimating pediatric general anesthesia exposure: Quantifying duration and risk.
Understanding the duration of pediatric general anesthesia exposure in contemporary practice is important for identifying groups at risk for long general anesthesia exposures and designing trials examining associations between general anesthesia exposure and neurodevelopmental outcomes. We performed a retrospective cohort analysis to estimate pediatric general anesthesia exposure duration during 2010-2015 using the National Anesthesia Clinical Outcomes Registry. A total of 1 548 021 pediatric general anesthetics were included. Median general anesthesia duration was 57 minutes (IQR: 28-86) with 90th percentile 145 minutes. Children aged <1 year had the longest median exposure duration (79 minutes, IQR: 39-119) with 90th percentile 210 minutes, and 13.7% of this very young cohort was exposed for >3 hours. High ASA physical status and care at a university hospital were associated with longer exposure times. While the vast majority (94%) of children undergoing general anesthesia are exposed for <3 hours, certain groups may be at increased risk for longer exposures. These findings may help guide the design of future trials aimed at understanding neurodevelopmental impact of prolonged exposure in these high-risk groups.


Nutrient and stoichiometric time series measurements of decomposing coarse detritus in freshwaters.
Decomposition of coarse detritus (e.g., dead organic matter larger than ~1 mm such as leaf litter or animal carcasses) in freshwater ecosystems is well described in terms of mass loss, particularly as rates that compress mass loss into one number (e.g., a first-order decay coefficient, or breakdown rate, "k"); less described are temporal changes in the elemental composition of these materials during decomposition, with important implications for elemental cycling from microbes to ecosystems. This stands in contrast with work in the terrestrial realm, where a focus on detrital elemental cycling has provided a sharper mechanistic understanding of decomposition, especially with specific processes such as immobilization and mineralization. Notably, freshwater ecologists often measure carbon (C), nitrogen (N), and phosphorus (P), and their stoichiometric ratios in decomposing coarse materials, including carcasses, wood, leaf litter, and more, but these measurements remain piecemeal. These detrital nutrients are measurements of the entire detrital-microbial complex and are integrative of numerous processes, especially nutrient immobilization and mineralization, and associated microbial growth and death. Thus, data relevant to an elemental, mechanistically focused decomposition ecology are available in freshwaters, but have not been fully applied to that purpose. We synthesized published detrital nutrient and stoichiometry measurements at a global scale, yielding 4038 observations comprising 810 decomposition time series (i.e., measurements within a defined cohort of decomposing material through time) to build a basis for understanding the temporality of elemental content in freshwater detritus. Specifically, the dataset focuses on temporally and ontogenetically (mass loss) explicit measurements of N, P, and stoichiometry (C:N, C:P, N:P). We also collected ancillary data, including detrital characteristics (e.g., species, lignin content), water physiochemistry, geographic location, incubation system type, and methodological variables (e.g., bag mesh size). These measurements are important to unlocking mechanistic insights into detrital ontogeny (the temporal trajectory of decomposing materials) that can provide a deeper understanding of heterotroph-driven C and nutrient cycling in freshwaters. Moreover, these data can help to bridge aquatic and terrestrial decomposition ecology, across plant or animal origin. By focusing on temporal trajectories of elements, this dataset facilitates cross-ecosystem comparisons of fundamental decomposition controls on elemental fluxes. It provides a strong starting point (e.g., via modeling efforts) for comparing processes such as immobilization and mineralization that are understudied in freshwaters. Time series from decomposing leaf litter, particularly in streams, are common in the dataset, but we also synthesized ontogenies of animal-based detritus, which tend to decompose rapidly compared with plant-based detritus that contains high concentrations of structural compounds such as lignin and cellulose. Although animal-based data were rare, comprising only three time series, their inclusion in this dataset underscores the opportunities to develop an understanding of decomposition that encompasses all detrital types, from carrion to leaf litter. There are no copyright or proprietary restrictions on the dataset; please cite this data paper when reusing these materials.


Low-dose lipopolysaccharide selectively sensitizes hypoxic ischemia-induced white matter injury in the immature brain.
Little is known about roles of inflammation and hypoxic ischemia (HI) in the generation of neuroinflammation and damage of blood-brain barrier (BBB) in the white matter (WM) that displays regional vulnerability in preterm infants. We investigated whether low-dose lipopolysaccharide (LPS) sensitizes HI-induced WM injury in postpartum (P) day 2 rat pups by selectively increasing neuroinflammation and BBB damage in the WM. Pups received LPS (0.05 mg/kg) (LPS + HI) or normal saline (NS + HI) followed by 90-min HI. LPS and NS group were the pups that had LPS or NS only. Myelin basic protein immunohistochemistry on P11 showed WM injury in LPS + HI group, but not in NS + HI, LPS, and NS groups. In contrast, no gray matter injury was found in the four groups. LPS + HI group also showed decreased number of oligodendrocytes in the WM 72-h postinsult. In the same brain region, increases of activated microglia, TNF-alpha expression, BBB leakage, and cleaved caspase-3 positive cells were much more prominent in LPS + HI group than in the other three groups 24-h postinsult. The oligodendrocytes were the major cells with cleaved caspase-3 expression. We concluded that low-dose LPS sensitized HI-induced WM injury in the immature brain by selectively up-regulating neuroinflammation and BBB damage in the WM.


Using a hybrid demand-allocation algorithm to enable distributional analysis of land use change patterns.
Future land use projections are needed to inform long-term planning and policy. However, most projections require downscaling into spatially explicit projection rasters for ecosystem service analyses. Empirical demand-allocation algorithms input coarse-level transition quotas and convert cells across the raster, based on a modeled probability surface. Such algorithms typically employ contagious and/or random allocation approaches. We present a hybrid seeding approach designed to generate a stochastic collection of spatial realizations for distributional analysis, by 1) randomly selecting a seed cell from a sample of n cells, then 2) converting patches of neighboring cells based on transition probability and distance to the seed. We generated a collection of realizations from 2001-2011 for the conterminous USA at 90m resolution based on varying the value of n, then computed forest area by fragmentation class and compared the results with observed 2011 forest area by fragmentation class. We found that realizations based on values of n ≤ 256 generally covered observed forest fragmentation at regional scales, for approximately 70% of assessed cases. We also demonstrate the potential of the seeding algorithm for distributional analysis by generating 20 trajectories of realizations from 2020-2070 from a single example scenario. Generating a library of such trajectories from across multiple scenarios will enable analysis of projected patterns and downstream ecosystem services, as well as their variation.


Induction of acyl-CoA-binding protein and its mRNA in 3T3-L1 cells by insulin during preadipocyte-to-adipocyte differentiation.
The induction of acyl-CoA-binding protein (ACBP) and ACBP mRNA was investigated in 3T3-L1 cells during growth and insulin-induced differentiation. The level of ACBP relative to both total soluble protein and DNA increased during insulin-stimulated conversion of 3T3-L1 cells from preadipocytes into fully developed adipocytes. So did the total rate of lipogenesis, as measured by incorporation of [1-14C]acetate. A similar increase in ACBP mRNA relative to total RNA was observed. These results therefore suggest that ACBP plays a specific role in the lipogenic process. However, this role might be indirect, as the increase in lipogenesis preceded the increase in ACBP. The significance of this finding is discussed.


Near-infrared indocyanine green videoangiography versus microvascular Doppler sonography in aneurysm surgery.
The quality of surgical treatment of intracranial aneurysms is determined by complete aneurysm occlusion and restoration of flow in the parent, branching and perforating vessels. In postoperative digital subtraction angiography (DSA), unexpected aneurysm residuals and vessel occlusions are frequently detected. Here, the value of two nearly noninvasive and cost-effective techniques for intraoperative flow evaluation (near-infrared indocyanine green video angiography (ICG-VA) and microvascular Doppler sonography (mDs)) is investigated in a prospective study. Over a period of 10 months, the authors surgically clipped 50 aneurysms under intraoperative pre- and post-clipping evaluation of flow in the parent, branching and perforating vessels and the aneurysm sack by the two techniques. Intraoperative applicability of each technique was compared to each other and to postoperative digital subtraction angiography as standard evaluation technique. Forty-five aneurysms were totally occluded without vessel compromise (90%). Intraoperatively, ICG-VA was considered useful in 43 cases (86%) and mDs in 44 cases (88%), respectively. Both techniques could compensate each other's weak points to a certain degree; but two branch occlusions (4%) and three neck remnants (6%) were revealed by postoperative DSA. Both techniques have specific drawbacks that could be compensated by each other, to a certain extent. Intraoperatively, ICG-VA and mDs should not be considered competitive, but complementary. This study implicates that the combination of both applications on a routine basis assures the quality of aneurysm surgery by nearly noninvasive and cost-effective techniques. However, DSA remains the gold standard for evaluation of aneurysm occlusion.


Enhancement Effect of Trypsin on Permeation of Clindamycin Phosphate Through Third-degree Burn Eschar.
Antimicrobial therapy remains to be the most important method of wound infection treatment. Systemically administered antimicrobials may not achieve therapeutic level in wound. On the other hand, in the absence of surgical debridement (due to any reason), most topically applied antimicrobials cannot penetrate the wound in therapeutic amount due to the presence of eschar. Burn eschar is a proteinous structure with some lipid components in which proteins seems to play an important role in the barrier effects of eschar. Therefore, in this study the effect of protein-acting enhancer (trypsin) on permeation of hydrophilic model drug (clindamycin phosphate) was investigated. To perform this investigation, permeation of saturated clindamycin phosphate was studied at 32°C through trypsin-treated and untreated eschar samples for 12 h using home-made static diffusion cells. Third-degree burn eschar samples were separated at the time of surgical debridement (7-14 days post burn) from burned patients. Before each experiment, eschar was hydrated for 12 h and samples were then treated with trypsin solution (1%, w/v) for 4 and 24 h. Clindamycin was measured by a HPLC method developed here. Results showed that after trypsin-treatment for 4 and 24 h, clindamycin phosphate permeation flux was increased significantly by about 1.5 and 2 times and permeation lag-time was decreased by about 2 and 1.3 times respectively. The present results show that permeation of drugs through burn eschar can be increased considerably by trypsin.


Serum Parathyroid Hormone Concentrations and Clinical Outcomes in ESRD: A Call for Targeted Clinical Trials.
Secondary hyperparathyroidism almost universally accompanies end-stage renal disease (ESRD). In some, but not all studies, elevated serum parathyroid hormone (PTH) concentrations are associated with increased fracture rates, cardiovascular disease, and mortality in ESRD. The serum concentration of PTH required for optimal bone health and reduced cardiovascular risk in such patients remains elusive. Recent clinical trials have failed to show substantial changes in morbidity and mortality following reductions of elevated serum PTH concentrations. In this review, we will assess some of the difficulties in evaluating elevated serum PTH concentrations, and their association with skeletal fractures and mortality in ESRD patients. We are of the opinion that in the context of ESRD, elevated PTH concentrations occur in conjunction with other comorbid conditions such as diabetes mellitus, malnutrition, hypertension, volume excess, preexisting heart disease, all of which have prevented establishing a precise association between elevated serum PTH concentrations and global or skeletal outcomes. Age, gender, and racial variability among groups make interpretation exceptionally difficult. Analysis of prevalent ESRD populations with secondary hyperparathyroidism should take all these factors into account. We suggest that future clinical trials which examine the usefulness of reductions in serum PTH concentrations be conducted in age, sex, and racially balanced groups, without or with minimal coexisting confounding disease. Furthermore, trials in such populations should have as their primary outcome a reduction in fractures rather than an alteration in mortality.


Influence of robotic shoal size, configuration, and activity on zebrafish behavior in a free-swimming environment.
In animal studies, robots have been recently used as a valid tool for testing a wide spectrum of hypotheses. These robots often exploit visual or auditory cues to modulate animal behavior. The propensity of zebrafish, a model organism in biological studies, toward fish with similar color patterns and shape has been leveraged to design biologically inspired robots that successfully attract zebrafish in preference tests. With an aim of extending the application of such robots to field studies, here, we investigate the response of zebrafish to multiple robotic fish swimming at different speeds and in varying arrangements. A soft real-time multi-target tracking and control system remotely steers the robots in circular trajectories during the experimental trials. Our findings indicate a complex behavioral response of zebrafish to biologically inspired robots. More robots produce a significant change in salient measures of stress, with a fast robot swimming alone causing more freezing and erratic activity than two robots swimming slowly together. In addition, fish spend more time in the proximity of a robot when they swim far apart than when the robots swim close to each other. Increase in the number of robots also significantly alters the degree of alignment of fish motion with a robot. Results from this study are expected to advance our understanding of robot perception by live animals and aid in hypothesis-driven studies in unconstrained free-swimming environments.


Enteroviral myocarditis in neonates.
Enteroviruses are a leading cause of viral infections in children. While most enteroviral infections are mild and self-limiting, severe disease such as a viral sepsis syndrome, myocarditis, hepatitis and meningoencephalitis may occur. We present two cases of neonatal enteroviral myocarditis. Cardiorespiratory failure occurred in both cases, and severe shock refractory to conventional treatment required support with extracorporeal membrane oxygenation (ECMO). One child with coxsackievirus B3 myocarditis failed to recover and died after 3 weeks on ECMO, while one child could be decannulated successfully after 9 days of ECMO and recovered completely subsequently. In conclusion, neonatal myocarditis has a very high mortality, and ECMO should be considered early in neonates with rapid clinical and echocardiographic deterioration despite adequate inotropic support.


The role of invasive monitoring in the resuscitation of major burns: a systematic review and meta-analysis.
Increasingly, in major hospitals invasive monitoring endpoints are utilised to guide the acute resuscitation of burns. The aim of this review is to evaluate effects of invasive monitoring for major burns patients (>20% total body surface area) to prevent early organ dysfunction. Five databases were searched for randomised controlled trials and cohort studies that evaluated invasive monitoring within the acute phase (first 24 hours). Invasive monitoring included transesophageal echocardiogram, central venous pressure measurement, and pulmonary artery catheterisation. Primary outcomes included multiple organ failure scores, renal and cardiac dysfunction measurements, compartment syndrome and lactate at 24 hours. Secondary outcomes included mortality and intensive care unit stay. Ten studies involving 401 major burns patients were included. Data pooled from four studies demonstrated significantly improved cardiac index at 24 hours compared to non-invasive endpoints (MD: 0.65, 95% CI: 0.46-0.82, P=0.00001). Five studies pooled showed significantly increased urine output with invasive monitoring (MD: 0.18, 95% CI: 0.03-0.34, P=0.02), whereas there was no difference in blood lactate levels (MD: -0.11, 95% CI: -0.44-0.22, P=0.43). There was a trend for lower mortality in invasive monitoring groups compared with non-invasive controls; however, the difference was not significant. There remains insufficient evidence to determine whether invasive monitoring to guide fluid resuscitation improves patient outcomes after major burn trauma. Although meta-analysis determined significantly improved cardiac index and urine output, further studies are required.


Longitudinal study of FM system use in nonacademic settings: effects on language development.
The overall objective of the present study was to assess the efficacy of FM system use in the home setting for a group of preschool children with mild-to-severe sensorineural hearing loss. Changes in language acquisition were monitored and compared with similar measures from a group of children who used hearing aids. Secondarily, the perceived benefits and practical problems associated with FM system use across a variety of nonacademic situations were documented. Ten children with mild-to-severe sensorineural hearing loss participated in a 2-yr longitudinal study investigating the efficacy of FM system use in the home setting. The subjects were divided into two groups: one group was instructed to use FM systems at home as often as possible while the other used only their personal hearing aids. Changes in language acquisition were monitored in both groups. Subjective benefit and the practical problems associated with use of FM systems outside of traditional academic environments were monitored via daily use logs, a weekly observation inventory, and a situational listening profile. The majority of children in both groups improved in all measures of language development over the study interval. Although there were relatively large individual differences in performance for some measures, no statistically significant differences between the FM and hearing aid users were found. However, some children in the FM group made unusually large gains in some aspects of language development over the study interval. In addition, both parents and children reported benefits of FM system use in specific listening situations. Throughout the 2-yr study, a number of practical problems associated with FM system use outside the classroom were identified. Formal language measures did not yield significant differences between the FM and HA groups, but some subjects had rates of language acquisition which suggested that FM system use may be beneficial in selected cases. In addition, subjective reports of FM system benefit suggest that appropriate use of the device may facilitate effective communication in a variety of listening situations. Although recent advances in FM system design may minimize some of the factors that reportedly restricted consistent FM use in this study, the complexities associated with the modes of operation and problems with FM interference remain issues that require consistent audiologic monitoring of FM system use in nonacademic environments.


Consent to discuss participation in research: a pilot study.
Equitable access to research studies needs to be increased for all patients. There is debate about which is the best approach to use to discuss participation in research in real-world clinical settings. We aimed to determine the feasibility of asking all clinical staff within one hospital Trust (an organisation that provides secondary health services within the English and Welsh National Health Service) to use a newly created form on the Trust's electronic patient records system, as a means of asking patients to consent to discuss participation in research (the opt-in approach). We also aimed to collect feedback from patients and clinicians about their views of the opt-in approach. Four pilot sites were selected in the Trust: two memory clinics, an adult mental health team and an acute adult ward. Data were collected in three phases: (1) for 6 months, pilot site staff were asked to complete a consent to discuss participation in research form with patients; (2) staff feedback on the form was collected through an online survey; and (3) patient feedback was collected through focus groups. Of 1779 patients attending services during the pilot period, 197 (11%) had a form completed by staff and 143 (8%) opted-in to finding out about research. Staff cited limited time, low priority and poor user experience of the electronic patient records system as reasons for low uptake of the form. Patients generally approved of the approach but offered suggestions for improvement. There were mixed results for adopting an opt-in approach; uptake was very low, limiting its value as an effective strategy for improving access to research. Alternative strategies to the opt-in approach, such as transparent opt out approaches, warrant consideration to maximise access to research within routine clinical care.


Comparison between rigid and soft poly-articulated prosthetic hands in non-expert myo-electric users shows advantages of soft robotics.
Notwithstanding the advancement of modern bionic hands and the large variety of prosthetic hands in the market, commercial devices still present limited acceptance and percentage of daily use. While commercial prostheses present rigid mechanical structures, emerging trends in the design of robotic hands are moving towards soft technologies. Although this approach is inspired by nature and could be promising for prosthetic applications, there is scant literature concerning its benefits for end-users and in real-life scenarios. In this work, we evaluate and assess the role and the benefits of soft robotic technologies in the field of prosthetics. We propose a thorough comparison between rigid and soft characteristics of two poly-articulated hands in 5 non-expert myo-electric prosthesis users in pre- and post-therapeutic training conditions. The protocol includes two standard functional assessments, three surveys for user-perception, and three customized tests to evaluate the sense of embodiment. Results highlight that rigid hands provide a more precise grasp, while soft properties show higher functionalities thanks to their adaptability to different requirements, intuitive use and more natural execution of activities of daily living. This comprehensive evaluation suggests that softness could also promote a quick integration of the system in non-expert users.


Pawtucket Heart Health Program point-of-purchase nutrition education program in supermarkets.
Point-of-purchase nutrition education in supermarkets is one intervention strategy of the Pawtucket Heart Health Program, a community cardiovascular disease prevention program in Pawtucket, Rhode Island. Using consumer intercept interviews, awareness of shelf labels and their effect on purchase behavior have been continuously evaluated. Between 1984 and 1988, the percent of shoppers who could identify correct labels increased from 11 percent to 24 percent (95% confidence intervals of difference: 7.17). The percent who reported they were encouraged to purchase the identified foods increased from 36 percent to 54 percent (95% CI of difference: 5.41).


Perceptual Learning in Children With Infantile Nystagmus: Effects on 2D Oculomotor Behavior.
To determine changes in oculomotor behavior after 10 sessions of perceptual learning on a letter discrimination task in children with infantile nystagmus (IN). Children with IN (18 children with idiopathic IN and 18 with oculocutaneous albinism accompanied by IN) aged 6 to 11 years were divided into two training groups matched on diagnosis: an uncrowded training group (n = 18) and a crowded training group (n = 18). Target letters always appeared briefly (500 ms) at an eccentric location, forcing subjects to quickly redirect their gaze. Training occurred twice per week for 5 consecutive weeks (3500 trials total). Norm data and test-retest values were collected from children with normal vision (n = 11). Outcome measures were: nystagmus characteristics (amplitude, frequency, intensity, and the expanded nystagmus acuity function); fixation stability (the bivariate contour ellipse area and foveation time); and saccadic eye movements (latencies and accuracy) made during a simple saccade task and a crowded letter-identification task. After training, saccadic responses of children with IN improved on the saccade task (latencies decreased by 14 ± 4 ms and gains increased by 0.03 ± 0.01), but not on the crowded letter task. There were also no training-induced changes in nystagmus characteristics and fixation stability. Although children with normal vision had shorter latencies in the saccade task (47 ± 14 ms at baseline), test-retest changes in their saccade gains and latencies were almost equal to the training effects observed in children with IN. Our results suggest that the improvement in visual performance after perceptual learning in children with IN is primarily due to improved sensory processing rather than improved two-dimensional oculomotor behavior.


Myriocin significantly increases the mortality of a non-mammalian model host during Candida pathogenesis.
Candida albicans is a major human pathogen whose treatment is challenging due to antifungal drug toxicity, drug resistance and paucity of antifungal agents available. Myrocin (MYR) inhibits sphingosine synthesis, a precursor of sphingolipids, an important cell membrane and signaling molecule component. MYR also has dual immune suppressive and antifungal properties, potentially modulating mammalian immunity and simultaneously reducing fungal infection risk. Wax moth (Galleria mellonella) larvae, alternatives to mice, were used to establish if MYR suppressed insect immunity and increased survival of C. albicans-infected insects. MYR effects were studied in vivo and in vitro, and compared alone and combined with those of approved antifungal drugs, fluconazole (FLC) and amphotericin B (AMPH). Insect immune defenses failed to inhibit C. albicans with high mortalities. In insects pretreated with the drug followed by C. albicans inoculation, MYR+C. albicans significantly increased mortality to 93% from 67% with C. albicans alone 48 h post-infection whilst AMPH+C. albicans and FLC+C. albicans only showed 26% and 0% mortalities, respectively. MYR combinations with other antifungal drugs in vivo also enhanced larval mortalities, contrasting the synergistic antifungal effect of the MYR+AMPH combination in vitro. MYR treatment influenced immunity and stress management gene expression during C. albicans pathogenesis, modulating transcripts putatively associated with signal transduction/regulation of cytokines, I-kappaB kinase/NF-kappaB cascade, G-protein coupled receptor and inflammation. In contrast, all stress management gene expression was down-regulated in FLC and AMPH pretreated C. albicans-infected insects. Results are discussed with their implications for clinical use of MYR to treat sphingolipid-associated disorders.


Robot-assisted stereotactic laser ablation in medically intractable epilepsy: operative technique.
Stereotactic laser ablation offers an advantage over open surgical procedures for treatment of epileptic foci, tumors, and other brain pathology. Robot-assisted stereotactic laser ablation could offer an accurate, efficient, minimally invasive, and safe method for placement of an ablation catheter into the target. To determine the feasibility of placement of a stereotactic laser ablation catheter into a brain lesion with the use of robotic assistance, via a safe, accurate, efficient, and minimally invasive manner. A laser ablation catheter (Visualase, Inc) was placed by using robotic guidance (ROSA, Medtech Surgical, Inc) under general anesthesia into a localized epileptogenic periventricular heterotopic lesion in a 19-year-old woman with 10-year refractory focal seizure history. The laser applicator (1.65 mm diameter) position was confirmed by using magnetic resonance imaging (MRI). Ablation using the Visualase system was performed under multiplanar imaging with real-time thermal imaging and treatment estimates in each plane. A postablation MRI sequence (T1 postgadolinium contrast injection) was used to immediately confirm the ablation. MRI showed accurate skin entry point and trajectory, with the applicator advanced to the lesion's distal boundary. Ablation was accomplished in less than 3 minutes of heating. The overall procedure, from time of skin incision to end of last ablation, was approximately 90 minutes. After confirmation of proper lesioning by using a T1 contrast-enhanced MRI, the applicator was removed, and the incision was closed using a single stitch. No hemorrhage or other untoward complication was visualized. The patient awoke without any complication, was observed overnight after admitting to a regular floor bed, and was discharged to home the following day. This technique, using a combination of Visualase laser ablation, ROSA robot, and intraoperative MRI, facilitated a safe, efficacious, efficient, and minimally invasive approach that could be used for placement of 1 or multiple electrodes in the future.


Structural and energetic basis of ALS-causing mutations in the atypical proline-tyrosine nuclear localization signal of the Fused in Sarcoma protein (FUS).
Mutations in the proline/tyrosine-nuclear localization signal (PY-NLS) of the Fused in Sarcoma protein (FUS) cause amyotrophic lateral sclerosis (ALS). Here we report the crystal structure of the FUS PY-NLS bound to its nuclear import receptor Karyopherinβ2 (Kapβ2; also known as Transportin). The FUS PY-NLS occupies the structurally invariant C-terminal arch of Kapβ2, tracing a path similar to that of other characterized PY-NLSs. Unlike other PY-NLSs, which generally bind Kapβ2 in fully extended conformations, the FUS peptide is atypical as its central portion forms a 2.5-turn α-helix. The Kapβ2-binding epitopes of the FUS PY-NLS consist of an N-terminal PGKM hydrophobic motif, a central arginine-rich α-helix, and a C-terminal PY motif. ALS mutations are found almost exclusively within these epitopes. Each ALS mutation site makes multiple contacts with Kapβ2 and mutations of these residues decrease binding affinities for Kapβ2 (K(D) for wild-type FUS PY-NLS is 9.5 nM) up to ninefold. Thermodynamic analyses of ALS mutations in the FUS PY-NLS show that the weakening of FUS-Kapβ2 binding affinity, the degree of cytoplasmic mislocalization, and ALS disease severity are correlated.


Three-dimensional adaptive coordinate transformations for the Fourier modal method.
The concepts of adaptive coordinates and adaptive spatial resolution have proved to be a valuable tool to improve the convergence characteristics of the Fourier Modal Method (FMM), especially for metallo-dielectric systems. Yet, only two-dimensional adaptive coordinates were used so far. This paper presents the first systematic construction of three-dimensional adaptive coordinate and adaptive spatial resolution transformations in the context of the FMM. For that, the construction of a three-dimensional mesh for a periodic system consisting of two layers of mutually rotated, metallic crosses is discussed. The main impact of this method is that it can be used with any classic FMM code that is able to solve the large FMM eigenproblem. Since the transformation starts and ends in a Cartesian mesh, only the transformed material tensors need to be computed and entered into an existing FMM code.


Left atrial appendage occlusion for stroke prevention in patients with atrial fibrillation: a systematic review and network meta-analysis of randomized controlled trials.
Atrial fibrillation (AF) is one of the leading causes of stroke. Risks associated with oral anticoagulation (OAC) limit adherence to recommended therapy. Left atrial appendage (LAA) occlusion is a treatment alternative in patients with AF. We performed a network meta-analysis (NMA) of randomized trials evaluating the efficacy of LAA occlusion compared with oral anticoagulant, antiplatelet, and placebo for stroke prevention. We also assessed the impact of LAA occlusion on mortality, major bleeding, and operative time. We searched MEDLINE, EMBASE, PubMed, and Cochrane Library for randomized trials comparing percutaneous or surgical LAA occlusion with standard of care in AF patients. Conventional meta-analysis found no difference between groups for stroke (5 trials, 1285 patients;RR 0.78, 95% CI 0.47-1.29), and a significant reduction in mortality (5 trials, 1285 patients; RR 0.71, 95% CI 0.51-0.99) favouring LAA occlusion. NMA demonstrated a trend towards reduction in stroke (OR 0.84, 95% CrI 0.47-1.55) and mortality (OR 0.69, 95% CrI 0.44-1.10) for LAA occlusion versus warfarin, but no statistically significant effect. Statistical ranking curves placed LAA occlusion as the most efficacious treatment on the outcomes of stroke and mortality when compared to warfarin, aspirin, or placebo. No significant differences between groups were seen in major bleeding or operative time for surgical trials. The overall quality of the evidence was low as assessed by GRADE. LAA occlusion appears to preserve the benefits of OAC therapy for stroke prevention in patients with AF, but the current evidence is of low quality.


Pain interference type and level guide the assessment process in chronic pain: Categorizing pain patients entering tertiary pain treatment with the Brief Pain Inventory.
Chronic pain patients enter treatment with different problem profiles making careful assessment a necessity for more individualized treatment plans. In this cross-sectional study we assigned 320 patients entering tertiary multidisciplinary pain treatment into four categories based on whether they scored low or high on the activity and the affective pain interference dimensions of the Brief Pain Inventory (BPI). To determine whether this categorization system delineates issues that should be assessed further, the categories were compared with ANOVA and MANOVA analyses on three domains: variables affecting physical well-being (body mass index, exercise, substance use), psychological resources (mood), and pain-specific psychological factors (pain anxiety, pain acceptance). The results indicated that subjects who scored low on both interference dimensions compared similarly in weight: mean Body Mass Index (BMI) 27.0 (SD 6.0) kg/m2, and exercise: mean of 2.4 (SD 1.7) exercising sessions over 20 minutes per week, to the general population, had no depressive symptoms on average: mean Beck Depression Index II (BDI-II) score 11.7 (SD 7.5), and had the most favorable psychological reactions to pain relative to the other categories: mean total Pain Anxiety Symptoms Scale-20 (PASS-20) score 36.4 (SD 17.9). In contrast, when interference was high on activity, more physical well-being problems were evident e.g. weight: mean BMI 31.0 (SD 7.3) kg/m2, diminished exercise: mean of 1.5 (SD 1.6) exercising sessions per week, and avoidance behavior: mean PASS-20 Escape/Avoidance subscale 3.7 (95% CI: 1.7 to 5.8) scores higher in comparison to activity interference remaining low. With high affective interference, more depressive symptoms: mean BDI-II score 17.7 (SD 7.3), and more cognitive pain anxiety: mean PASS-20 Cognitive Anxiety subscale 2.8 (95% CI 0.7 to 4.8) scores higher in comparison to affective interference remaining low, emerged. Having high interference on both dimensions indicated accumulated risks for reduced physical well-being: mean BMI 29.9 (SD 6.1) kg/m2, mean of 1.2 (SD 1.7) exercising sessions per week, mood problems: mean BDI-II 20.3 (SD 10.6), and negative psychological reactions to pain: mean total PASS-20 score 53.2 (18.4). The results suggest that low interference on both dimensions may allow assessment with only physician consultations, while high interference on either dimension may call attention to distinct issues to be addressed with the help of a physiotherapist or a psychologist, whereas high interference on both dimensions highlights the need for a full multidisciplinary assessment.


Conserved antigen structures and antibody-driven variations on foot-and-mouth disease virus serotype A revealed by bovine neutralizing monoclonal antibodies.
Foot-and-mouth disease virus (FMDV) serotype A is antigenically most variable within serotypes. The structures of conserved and variable antigenic sites were not well resolved. Here, a historical A/AF72 strain from A22 lineage and a latest A/GDMM/2013 strain from G2 genotype of Sea97 lineage were respectively used as bait antigen to screen single B cell antibodies from bovine sequentially vaccinated with A/WH/CHA/09 (G1 genotype of Sea97 lineage), A/GDMM/2013 and A/AF72 antigens. Total of 39 strain-specific and 5 broad neutralizing antibodies (bnAbs) were isolated and characterized. Two conserved antigenic sites were revealed by the Cryo-EM structures of FMDV serotype A with two bnAbs W2 and W125. The contact sites with both VH and VL of W125 were closely around icosahedral threefold axis and covered the B-C, E-F, and H-I loops on VP2 and the B-B knob and H-I loop on VP3; while contact sites with only VH of W2 concentrated on B-B knob, B-C and E-F loops on VP3 scattering around the three-fold axis of viral particle. Additional highly conserved epitopes also involved key residues of VP158, VP1147 and both VP272 / VP1147 as determined respectively by bnAb W153, W145 and W151-resistant mutants. Furthermore, the epitopes recognized by 20 strain-specific neutralization antibodies involved the key residues located on VP3 68 for A/AF72 (11/20) and VP3 175 position for A/GDMM/2013 (9/19), respectively, which revealed antigenic variation between different strains of serotype A. Analysis of antibody-driven variations on capsid of two virus strains showed a relatively stable VP2 and more variable VP3 and VP1. This study provided important information on conserve and variable antigen structures to design broad-spectrum molecular vaccine against FMDV serotype A.


Development of a technique for quantification of reticulocytes and assessment of erythrocyte regenerative capacity in birds.
To develop a reticulocyte classification scheme, optimize an avian reticulocyte staining protocol, and compare the percentages of reticulocyte types with polychromatophil percentage in blood samples from birds. Blood samples from a red-tailed hawk and 31 ill birds. A single blood sample obtained from a red-tailed hawk (Buteo jamaicensis) was used to optimize the staining protocol. For optimization of the staining protocol, 4 dilutions of whole blood with new methylene blue stain and 4 incubation times were evaluated. From samples submitted for avian CBCs, EDTA-anticoagulated whole blood samples from 31 ill birds were randomly selected and examined to compare polychromatophil and reticulocyte percentages. Reticulocyte staining was performed in all samples by use of a 1:3 (whole blood to new methylene blue) dilution with incubation for 10 minutes at room temperature (approx 22 degrees C); reticulocytes were assessed as a percentage of 1,000 RBCs by 2 independent observers. In Wright-Giemsa-stained blood smears, a polychromatophil percentage was similarly determined. 4 avian reticulocyte types were defined: ring-form reticulocytes, aggregate reticulocytes, and 2 subcategories of punctate reticulocytes. A reticulocyte-staining protocol was optimized. Interobserver and intraobserver variations in assessment of reticulocyte and polychromatophil percentages were not significant. A strong positive correlation (Spearman coefficient of rank correlation [rho] = 0.978) was identified between the percentage of polychromatophils and the percentage of ring-form reticulocytes. Results indicated that quantification of ring-form reticulocytes provides an accurate assessment of erythrocyte regenerative capacity in birds.


A Flippase-Mediated GAL80/GAL4 Intersectional Resource for Dissecting Appendage Development in Drosophila.
Drosophila imaginal discs provide an ideal model to study processes important for cell signaling and cell specification, tissue differentiation, and cell competition during development. One challenge to understanding genetic control of cellular processes and cell interactions is the difficulty in effectively targeting a defined subset of cells in developing tissues in gene manipulation experiments. A recently developed Flippase-induced intersectional GAL80/GAL4 repression method incorporates several gene manipulation technologies in Drosophila to enable such fine-scale dissection in neural tissues. In particular, this approach brings together existing GAL4 transgenes, newly developed enhancer-trap flippase transgenes, and GAL80 transgenes flanked by Flippase recognition target sites. The combination of these tools enables gene activation/repression in particular subsets of cells within a GAL4 expression pattern. Here, we expand the utility of a large collection of these enhancer-trap flippase transgenic insertion lines by characterizing their expression patterns in third larval instar imaginal discs. We screened 521 different enhancer-trap flippase lines and identified 28 that are expressed in imaginal tissues, including two transgenes that show sex-specific expression patterns. Using a line that expresses Flippase in the wing imaginal disc, we demonstrate the utility of this intersectional approach for studying development by knocking down gene expression of a key member of the planar cell polarity pathway. The results of our experiments show that these enhancer-trap flippase lines enable fine-scale manipulation in imaginal discs.


Aneuploidy-induced delaminating cells drive tumorigenesis in Drosophila epithelia.
Genomic instability has been observed in essentially all sporadic carcinomas. Here we use Drosophila epithelial cells to address the role of chromosomal instability in cancer development as they have proved useful for elucidating the molecular mechanisms underlying tumorigenic growth. We first show that chromosomal instability leads to an apoptotic response. Interestingly, this response is p53 independent, as opposed to mammalian cells, and depends on the activation of the c-Jun N-terminal kinase (JNK) signaling cascade. When prevented from undergoing programmed cell death (PCD), chromosomal instability induces neoplasic overgrowth. These tumor-like tissues are able to grow extensively and metastasize when transplanted into the abdomen of adult hosts. Detailed analysis of the tumors allows us to identify a delaminating cell population as the critical one in driving tumorigenesis. Cells loose their apical-basal polarity, mislocalize DE-cadherin, and delaminate from the main epithelium. A JNK-dependent transcriptional program is activated specifically in delaminating cells and drives nonautonomous tissue overgrowth, basement membrane degradation, and invasiveness. These findings unravel a general and rapid tumorigenic potential of genomic instability, as opposed to its proposed role as a source of mutability to select specific tumor-prone aneuploid cells, and open unique avenues toward the understanding of the role of genomic instability in human cancer.


Mapping the structure of perceptions in helping networks of Alaska Natives.
This paper introduces a new method for acquiring and interpreting data on cognitive (or perceptual) networks. The proposed method involves the collection of multiple reports on randomly chosen pairs of individuals, and statistical means for aggregating these reports into data of conventional sociometric form. We refer to the method as "perceptual tomography" to emphasize that it aggregates multiple 3rd-party data on the perceived presence or absence of individual properties and pairwise relationships. Key features of the method include its low respondent burden, flexible interpretation, as well as its ability to find "robust intransitive" ties in the form of perceived non-edges. This latter feature, in turn, allows for the application of conventional balance clustering routines to perceptual tomography data. In what follows, we will describe both the method and an example of the implementation of the method from a recent community study among Alaska Natives. Interview data from 170 community residents is used to ascribe 4446 perceived relationships (2146 perceived edges, 2300 perceived non-edges) among 393 community members, and to assert the perceived presence (or absence) of 16 community-oriented helping behaviors to each individual in the community. Using balance theory-based partitioning of the perceptual network, we show that people in the community perceive distinct helping roles as structural associations among community members. The fact that role classes can be detected in network renderings of "tomographic" perceptual information lends support to the suggestion that this method is capable of producing meaningful new kinds of data about perceptual networks.


Does metabolic compensation explain the majority of less-than-expected weight loss in obese adults during a short-term severe diet and exercise intervention?
We investigated to what extent changes in metabolic rate and composition of weight loss explained the less-than-expected weight loss in obese men and women during a diet-plus-exercise intervention. In all, 16 obese men and women (41 ± 9 years; body mass index (BMI) 39 ± 6 kg m(-2)) were investigated in energy balance before, after and twice during a 12-week very-low-energy diet(565-650 kcal per day) plus exercise (aerobic plus resistance training) intervention. The relative energy deficit (EDef) from baseline requirements was severe (74%-87%). Body composition was measured by deuterium dilution and dual energy X-ray absorptiometry, and resting metabolic rate (RMR) was measured by indirect calorimetry. Fat mass (FM) and fat-free mass (FFM) were converted into energy equivalents using constants 9.45 kcal per g FM and 1.13 kcal per g FFM. Predicted weight loss was calculated from the EDef using the '7700 kcal kg(-1) rule'. Changes in weight (-18.6 ± 5.0 kg), FM (-15.5 ± 4.3 kg) and FFM (-3.1 ± 1.9 kg) did not differ between genders. Measured weight loss was on average 67% of the predicted value, but ranged from 39% to 94%. Relative EDef was correlated with the decrease in RMR (R=0.70, P<0.01), and the decrease in RMR correlated with the difference between actual and expected weight loss (R=0.51, P<0.01). Changes in metabolic rate explained on average 67% of the less-than-expected weight loss, and variability in the proportion of weight lost as FM accounted for a further 5%. On average, after adjustment for changes in metabolic rate and body composition of weight lost, actual weight loss reached 90% of the predicted values. Although weight loss was 33% lower than predicted at baseline from standard energy equivalents, the majority of this differential was explained by physiological variables. Although lower-than-expected weight loss is often attributed to incomplete adherence to prescribed interventions, the influence of baseline calculation errors and metabolic downregulation should not be discounted.


Crossmodal integration in the primate superior colliculus underlying the preparation and initiation of saccadic eye movements.
Saccades to combined audiovisual stimuli often have reduced saccadic reaction times (SRTs) compared with those to unimodal stimuli. Neurons in the intermediate/deep layers of the superior colliculus (dSC) are capable of integrating converging sensory inputs to influence the time to saccade initiation. To identify how neural processing in the dSC contributes to reducing SRTs to audiovisual stimuli, we recorded activity from dSC neurons while monkeys generated saccades to visual or audiovisual stimuli. To evoke crossmodal interactions of varying strength, we used auditory and visual stimuli of different intensities, presented either in spatial alignment or to opposite hemifields. Spatially aligned audiovisual stimuli evoked the shortest SRTs. In the case of low-intensity stimuli, the response to the auditory component of the aligned audiovisual target increased the activity preceding the response to the visual component, accelerating the onset of the visual response and facilitating the generation of shorter-latency saccades. In the case of high-intensity stimuli, the auditory and visual responses occurred much closer together in time and so there was little opportunity for the auditory stimulus to influence previsual activity. Instead, the reduction in SRT for high-intensity, aligned audiovisual stimuli was correlated with increased premotor activity (activity after visual burst but preceding saccade-aligned burst). These data provide a link between changes in neural activity related to stimulus modality with changes in behavior. They further demonstrate how crossmodal interactions are not limited to the initial sensory activity but can also influence premotor activity in the SC.


Upper extremity dog bite wounds and infections.
Upper extremity dog bite wounds comprise a large percentage of all mammalian bite wounds. The purpose of the study was to assess the bacteriology of patients presenting with such injuries to the emergency room that required consultation by a hand surgeon. The study also analyzed the effect of delayed intervention on growth of invasive pathogens, on the incidence of multiple pathogens, on treatment interventions, and on length of hospital stay. Objective data and subjective descriptions of the wound were collected on 32 patients who presented to Chicago area hospitals. The authors retrospectively analyzed the data and grouped the patients into two categories based on time of intervention: early or those treated within 48 hours, and delayed to include those treated after 48 hours. Incidence of bacterial growth and Pasteurella species growth in cultures was similar to that reported in the literature. Delayed patients had a significantly higher incidence of positive bacterial growth from wound cultures (100%) compared with nondelayed patients (54%). Delayed patients also had a higher incidence of treatment intervention (delayed group 86% surgical irrigation and debridement compared with 48% for the early group). There was a trend toward increased length of hospital stay (delayed group 4.6 days compared with 2.6 days), although this was not significant. The growth of multiple pathogens between the two groups was similar and not significant (delayed group 43% compared with 54% early group).


Standardization of broth microdilution method for Mycobacterium tuberculosis.
Indirect drug susceptibility tests of Mycobacterium tuberculosis was done to investigate the accuracy and feasibility of a broth microdilution method (BMM) for determining minimal inhibitory concentrations of conventional drugs against M. tuberculosis. Test drugs included isoniazid (H), rifampicin (R), ethambutol (E), streptomycin (S) and pyrazinamide (Z). Fifty isolates of M. tuberculosis from patients who had never received drug therapy, and H37Rv strain for control, were evaluated in the system. When comparing this method with the gold standard proportional method in Lowenstein-Jensen medium, sensitivity of 100% for all drugs and specifities of 91, 100, 96, 98 and 85% were observed respectively for H, R, E, S and Z. The BMM was read faster (14-20 days) than the proportional method (20-28 days). The microdilution method evaluated allows the testing of multiple drugs in multiple concentrations. It is easy to perform and does not require special equipment or expensive supplies. In contrast to radiometric method it does not use radioactive material.


Molecular beacon-enabled purification of living cells by targeting cell type-specific mRNAs.
Molecular beacons (MBs) are dual-labeled oligonucleotides that fluoresce only in the presence of complementary mRNA. The use of MBs to target specific mRNAs allows sorting of specific cells from a mixed cell population. In contrast to existing approaches that are limited by available surface markers or selectable metabolic characteristics, the MB-based method enables the isolation of a wide variety of cells. For example, the ability to purify specific cell types derived from pluripotent stem cells (PSCs) is important for basic research and therapeutics. In addition to providing a general protocol for MB design, validation and nucleofection into cells, we describe how to isolate a specific cell population from differentiating PSCs. By using this protocol, we have successfully isolated cardiomyocytes differentiated from mouse or human PSCs (hPSCs) with ∼ 97% purity, as confirmed by electrophysiology and immunocytochemistry. After designing MBs, their ordering and validation requires 2 weeks, and the isolation process requires 3 h.


Temporally Unconstrained Decoding Reveals Consistent but Time-Varying Stages of Stimulus Processing.
In this article, we propose a method to track trial-specific neural dynamics of stimulus processing and decision making with high temporal precision. By applying this novel method to a perceptual template-matching task, we tracked representational brain states associated with the cascade of neural processing, from early sensory areas to higher order areas that are involved in integration and decision making. We address a major limitation of the traditional decoding approach: that it relies on consistent timing of these processes over trials. Using a TUDA approach, we found that the timing of the cognitive processes involved in perceptual judgments can vary considerably over trials. This revealed that the sequence of processing states was consistent for all subjects and trials, even when the timing of these states varied. Furthermore, we found that the specific timing of states on each trial was related to the quality of performance over trials. Altogether, this work not only highlights the serious pitfalls and misleading interpretations that result from assuming stimulus processing to be synchronous across trials but can also open important avenues to investigate learning and quantify plasticity.


The epidemiology of HSV-2 infection and its association with HIV infection in four urban African populations.
To estimate age- and sex-specific herpes simplex virus type-2 (HSV-2) prevalence in urban African adult populations and to identify factors associated with infection. Cross-sectional, population-based samples of about 2000 adults interviewed in each of the following cities: Cotonou, Benin; Yaoundé, Cameroon; Kisumu, Kenya and Ndola, Zambia. Consenting study participants were tested for HIV, HSV-2 and other sexually transmitted infections. HSV-2 prevalence was over 50% among women and over 25% among men in Yaoundé, Kisumu and Ndola, with notably high rates of infection among young women in Kisumu and Ndola (39% and 23%, respectively, among women aged 15-19 years). The prevalence in Cotonou was lower (30% in women and 12% in men). Multivariate analysis showed that HSV-2 prevalence was significantly associated with older age, ever being married, and number of lifetime sexual partners, in almost all cities and both sexes. There was also a strong, consistent association with HIV infection. Among women, the adjusted odds ratios for the association between HSV-2 and HIV infections ranged from 4.0 [95% confidence interval (CI) = 2.0-8.0] in Kisumu to 5.5 (95% CI = 1.7-18) in Yaoundé, and those among men ranged from 4.6 (95% CI = 2.7-7.7) in Ndola to 7.9 (95% CI = 4.1-15) in Kisumu. HSV-2 infection is highly prevalent in these populations, even at young ages, and is strongly associated with HIV at an individual level. At a population level, HSV-2 prevalence was highest in Kisumu and Ndola, the cities with the highest HIV rates, although rates were also high among women in Yaoundé, where there are high rates of partner change but relatively little HIV infection. The high prevalence of both infections among young people underlines the need for education and counselling among adolescents.