Effects of computerized guidelines for managing heart disease in primary care.
Electronic information systems have been proposed as one means to reduce medical errors of commission (doing the wrong thing) and omission (not providing indicated care). To assess the effects of computer-based cardiac care suggestions. A randomized, controlled trial targeting primary care physicians and pharmacists. A total of 706 outpatients with heart failure and/or ischemic heart disease. Evidence-based cardiac care suggestions, approved by a panel of local cardiologists and general internists, were displayed to physicians and pharmacists as they cared for enrolled patients. Adherence with the care suggestions, generic and condition-specific quality of life, acute exacerbations of their cardiac disease, medication compliance, health care costs, satisfaction with care, and physicians' attitudes toward guidelines. Subjects were followed for 1 year during which they made 3,419 primary care visits and were eligible for 2,609 separate cardiac care suggestions. The intervention had no effect on physicians' adherence to the care suggestions (23% for intervention patients vs 22% for controls). There were no intervention-control differences in quality of life, medication compliance, health care utilization, costs, or satisfaction with care. Physicians viewed guidelines as providing helpful information but constraining their practice and not helpful in making decisions for individual patients. Care suggestions generated by a sophisticated electronic medical record system failed to improve adherence to accepted practice guidelines or outcomes for patients with heart disease. Future studies must weigh the benefits and costs of different (and perhaps more Draconian) methods of affecting clinician behavior.


Physiological response properties of displaced amacrine cells of the adult ferret retina.
The ganglion cell layer (GCL) of the mammalian retina contains a large number of neurons called displaced amacrine cells (DACs) that do not project to the optic nerve. However, with the exception of the rabbit starburst amacrine cell little is known regarding the function of this large population due to the difficulty experienced in making physiological recordings from these neurons. We have overcome these difficulties and have used whole-cell patch-clamp techniques to examine the intrinsic membrane properties of DACs in the ferret retina. Our results indicate a large degree of diversity in their intrinsic membrane properties. In response to maintained depolarizing current injection, DACs responded with graded depolarization or by eliciting either transient or sustained bursts of spiking activity. At the resting membrane potential, 10% of the DACs generated spontaneous spikes in either an apparently random manner or at the peak of intrinsic waves of depolarization. The resting membrane activity of the remaining DACs recorded could be classified into three groups that were quiescent (28%), had robust uncorrelated synaptic activity (30%), or underwent slow waves of depolarization (42%). Diversity was also revealed in the membrane currents recorded in voltage-clamp where some DACs were quiescent (19%), or exhibited robust nonrhythmic synaptic events (42%). The remaining DACs exhibited waves of oscillatory activity (39%), characterized by either rhythmic bursts of synaptic events (17%) or slow inward currents (22%). Bath application of 50 microM biccuculine or 150 microM picrotoxin had no effect on the waves of activity, however, the gap junction blocker, carbenoxolone (100 microm), blocked both oscillatory patterns. By including Lucifer yellow and biocytin in the recording pipette, it was possible to determine the morphology of recorded neurons and group them based on dendritic extent as small-, medium-, or large-field DACs. There were few relationships between these morphologically defined groups and their intrinsic membrane properties. The present study provides the first in-depth examination of the intrinsic membrane properties of DACs in the ferret retina and provides new insights into the potential roles these neurons play in the processing of visual information in the mammalian retina.


Poverty and disability in low- and middle-income countries: A systematic review.
Disability and poverty are believed to operate in a cycle, with each reinforcing the other. While agreement on the existence of a link is strong, robust empirical evidence substantiating and describing this potential association is lacking. Consequently, a systematic review was undertaken to explore the relationship between disability and economic poverty, with a focus on the situation in low and middle income countries (LMICs). Ten electronic databases were searched to retrieve studies of any epidemiological design, published between 1990-March 2016 with data comparing the level of poverty between people with and without disabilities in LMICs (World Bank classifications). Poverty was defined using economic measures (e.g. assets, income), while disability included both broad assessments (e.g. self-reported functional or activity limitations) and specific impairments/disorders. Data extracted included: measures of association between disability and poverty, population characteristics and study characteristics. Proportions of studies finding positive, negative, null or mixed associations between poverty and disability were then disaggregated by population and study characteristics. From the 15,500 records retrieved and screened, 150 studies were included in the final sample. Almost half of included studies were conducted in China, India or Brazil (n = 70, 47%). Most studies were cross-sectional in design (n = 124, 83%), focussed on specific impairment types (n = 115, 77%) and used income as the measure for economic poverty (n = 82, 55%). 122 studies (81%) found evidence of a positive association between disability and a poverty marker. This relationship persisted when results were disaggregated by gender, measure of poverty used and impairment types. By country income group at the time of data collection, the proportion of country-level analyses with a positive association increased with the rising income level, with 59% of low-income, 67% of lower-middle and 72% of upper-middle income countries finding a positive relationship. By age group, the proportion of studies reporting a positive association between disability and poverty was lowest for older adults and highest for working-age adults (69% vs. 86%). There is strong evidence for a link between disability and poverty in LMICs and an urgent need for further research and programmatic/policy action to break the cycle.


There may be more to reaching than meets the eye: re-thinking optic ataxia.
Optic ataxia (OA) is generally thought of as a disorder of visually guided reaching movements that cannot be explained by any simple deficit in visual or motor processing. In this paper we offer a new perspective on optic ataxia; we argue that the popular characterisation of this disorder is misleading and is unrepresentative of the pattern of reaching errors typically observed in OA patients. We begin our paper by reviewing recent neurophysiological, neuropsychological, and functional brain imaging studies that have led to the proposal that the medial parietal cortex in the vicinity of the parietal-occipital junction (POJ) - the key anatomical site associated with OA - represents reaching movements in eye-centred coordinates, and that this ability is impaired in optic ataxia. Our perspective stresses the importance of the POJ and superior parietal regions of the human PPC for representing reaching movements in both extrinsic (eye-centred) and intrinsic (postural) coordinates, and proposes that it is the ability to simultaneously represent multiple spatial locations that must be directly compared with one another that is impaired in non-foveal OA patients. In support of this idea we review recent fMRI and behavioural studies conducted by our group that have investigated the anatomical correlates of posturally guided movements, and the movements guided by postural cues in patients presenting with optic ataxia.


Effect of repeat-sprint training in hypoxia on post-exercise interleukin-6 and F2-isoprostanes.
This investigation examined the oxidative stress (F2-Isoprostane; F2-IsoP) and inflammatory (interleukin-6; IL-6) responses to repeat-sprint training in hypoxia (RSH). Ten trained male team sport athletes performed 3(sets)*9(repetitions)*5 s cycling sprints in simulated altitude (3000 m) and sea-level conditions. Mean and peak sprint power output (MPO and PPO) were recorded, and blood samples were collected pre-exercise, and again at 8 and 60 min post-exercise. Both MPO and PPO were significantly reduced in hypoxia (compared to sea-level) in the second (MPO: 855 ± 89 vs. 739 ± 95 W, p = .006; PPO: 1024 ± 114 vs. 895 ± 112 W, p = .010) and third (MPO: 819 ± 105 vs. 686 ± 83 W, p = .008; PPO: 985 ± 125 vs. 834 ± 99 W, p = .008) sets, respectively. IL-6 was significantly increased from pre- to 1 h post-exercise in both hypoxia (0.7 ± 0.2 vs. 2.4 ± 1.4 pg/mL, p = .004) and sea-level conditions (0.7 ± 0.2 vs. 1.6 ± 0.3 pg/mL, p < .001), with a large effect (d = 0.80) suggesting higher IL-6 levels of post-hypoxia. F2-IsoP was significantly lower 1 h post-exercise in both the hypoxic (p = .005) and sea-level (p = .002) conditions, with no differences between trials. While hypoxia can impact on exercise intensity and may result in greater post-exercise inflammation, it appears to have little effect on oxidative stress. These results indicate that team sport organisations with ready access to hypoxic training facilities could confidently administer RSH without significantly increasing the post-exercise inflammatory or oxidative stress response.


Musculoskeletal disorders among operators of visual display terminals.
Using a visual display terminal (VDT) is today a common occupational task with both benefits and hazards. One of the hazards is the occurrence of musculoskeletal disorders. This paper examines the possible causes of such disorders and suggests some preventive strategies. The debate on the relationship between musculoskeletal disorders and VDT usage usually centers around occupational factors (eg, constrained posture, poor ergonomic design of the workplace, equipment design), work-related psychological factors (eg, perceived high job demands, mundane, boring and repetitive job activity, little control, poor support from colleagues and superiors), and psychosocial factors (eg, biodemographic characteristics such as age, previous musculoskeletal injuries, emotional stress, family burden, environmental factors). Improving the ergonomic design of VDT workstations, changing occupational legislation, and improving occupational health services have been suggested as means to decrease the incidence of musculoskeletal disorders among VDT workers. Much research with a multidisciplinary approach is still needed.


Molecular and pathotypic characterization of new Xanthomonas oryzae strains from West Africa.
DNA polymorphism analysis and pathogenicity assays were used to characterize strains of Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola collected from rice leaves in West Africa. Restriction fragment length polymorphism (RFLP), repetitive sequence-based polymerase chain reaction, fluorescent amplified fragment-length polymorphism (FAFLP) analyses were assessed for molecular characterization, while pathogenicity was tested by leaf clipping and leaf infiltration. Dendrograms were generated for the data sets obtained from RFLP analysis and repetitive polymerase chain reaction suggesting that the interrelationships between strains were dependent on the technique used. In all cases, data showed that African strains of X. oryzae pv. oryzae form a group genetically distant from Asian strains. FAFLP analyses separated the X. oryzae strains into three groups with significant bootstrap values. A specific and intriguing feature of African strains of X. oryzae pv. oryzae is a reduction in the number of insertion sequence elements and transcription activator-like (avrBs3/pthA) effector genes, based on the molecular markers employed in the study. In addition, pathogenicity assays conducted with African strains of X. oryzae pv. oryzae on a series of nearly isogenic lines (NILs) identified three new races. Finally, leaf infiltration assays revealed the capacity of African strains of X. oryzae pv. oryzae to induce a nonhost hypersensitive response in Nicotiana benthamiana, in contrast with Asian X. oryzae pv. oryzae and X. oryzae pv. oryzicola strains. Our results reveal substantial differences between genomic characteristics of Asian and African strains of X. oryzae pv. oryzae.


Redox properties of a single (7,5)single-walled carbon nanotube determined by an in situ photoluminescence spectroelectrochemical method.
The determination of electronic states of single-walled carbon nanotubes (SWNTs) has been a central issue in science and nanotechnology of carbon nanotubes. We here describe the oxidation and reduction potentials of a single SWNT determined by in situ photoluminescence (PL) spectroelectrochemical measurements. By PL imaging and single SWNT PL spectroscopy, the stepwise quenching behavior of the PL from a single (7,5)SWNT was detected as the outer-applied potentials increased. Based on the analysis of the obtained potential-dependent PL plots using the Nernst equation, the oxidation and reduction potentials of the (7,5) tube are successfully determined as 0.41 V and -0.38 V vs. Ag/AgCl, respectively, which shift from those of the bulk (7,5)SWNTs. We further observed a PL blueshift and narrowing of the line width as the external-applied potential to the single SWNT increases. The present results are important for understanding the electronic properties of a single (n,m)SWNT and its applications.


A small-angle neutron and static light scattering study of micelles formed in aqueous mixtures of a nonionic alkylglucoside and an anionic surfactant.
The size and shape of micelles formed in aqueous mixtures of the anionic surfactant sodium dodecyl sulfate (SDS) and the nonionic sugar-based surfactant n-decyl beta-D-glucopyranoside (C(10)G) at different concentrations of added salt have been investigated with small-angle neutron and static light scattering. Rather small prolate ellipsoidal micelles form in the absence of added salt and at [NaCl] = 10 mM in D(2)O. The micelles grow considerably in length to large rods as the electrolyte concentration is raised to [NaCl] = 0.1 M. In excess of nonionic surfactant ([SDS]/[C(10)G] = 1:3) at [NaCl] = 0.1 M in D(2)O, several thousands of Angstroms long wormlike micelles are observed. Most interestingly, a conspicuously large isotope solvent effect was observed from static light scattering data according to which micelles formed at [SDS]/[C(10)G] = 1:3 and [NaCl] = 0.1 M in H(2)O are at least five times smaller than micelles formed in the corresponding samples in D(2)O.


Is magnetotherapy applied to bilateral hips effective in ankylosing spondylitis patients? A randomized, double-blind, controlled study.
This double-blind, randomized controlled study was conducted with the aim to investigate the effect of magnetic field therapy applied to the hip region on clinical and functional status in ankylosing spondylitis (AS) patients. Patients with AS (n = 66) who were diagnosed according to modified New York criteria were enrolled in this study. Patients were randomly divided in two groups. Participants were randomly assigned to receive magnetic field therapy (2 Hz) (n = 35), or placebo magnetic field therapy (n = 31) each hip region for 20 min. Patients in each group were given heat pack and short-wave treatments applied to bilateral hip regions. Both groups had articular range of motion and stretching exercises and strengthening exercises for surrounding muscles for the hip region as well as breathing and postural exercises by the same physical therapist. These treatment protocols were continued for a total of 15 sessions (1 session per day), and patients were examined by the same physician at months 1, 3 and 6. Visual analogue scale (VAS) pain, VAS fatigue, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrologic Index (BASMI), DFI, Harris hip assessment index and Ankylosing Spondylitis Quality of Life scale (ASQOL) were obtained at the beginning of therapy and at month 1, month 3 and month 6 for each patient. There were no significant differences between groups in the VAS pain, VAS fatigue, morning stiffness, BASDAI, BASFI, BASMI, DFI, Harris hip assessment index and ASQoL at baseline, month 1, month 3 or month 6 (p > 0.05). Further randomized, double-blind controlled studies are needed in order to establish the evidence level for the efficacy of modalities with known analgesic and anti-inflammatory action such as magnetotherapy, particularly in rheumatic disorders associated with chronic pain.


The Importance of Sexual History Taking for PrEP Comprehension Among Young People of Color.
Despite demonstrated efficacy, uptake of pre-exposure prophylaxis (PrEP) remains low, especially among highest priority populations. This study examined four PrEP messaging factors hypothesized to impact comprehension of PrEP educational information: (1) modality (video versus in-person message delivery); (2) frame (risk versus health focus); (3) specificity (gist versus verbatim efficacy information); and (4) sexual history (administered either before or after PrEP education). We examined message comprehension among 157 young people of color (YPoC) eligible for PrEP, using a series of multiple choice questions. Overall, 65.6 % (n = 103) got all message comprehension questions correct. In multivariate analyses, engaging in a sexual history before receiving PrEP education was associated with increased odds of message comprehension (aOR 2.23; 95 % CI 1.06-4.72). This effect was even stronger among those who received PrEP education via video (aOR 3.53; 95 % CI 1.16-10.81) compared to via health educator. This research underscores the importance of sexual history-taking as part of PrEP education and clinical practice for YPoC, and suggests that engaging patients in a sexual history prior to providing them with PrEP education may be key to increasing comprehension.


Trends in socioeconomic inequalities in self-assessed health in 17 European countries between 1990 and 2010.
Between the 1990s and 2000s, relative inequalities in all-cause mortality increased, whereas absolute inequalities decreased in many European countries. Whether similar trends can be observed for inequalities in other health outcomes is unknown. This paper aims to provide a comprehensive overview of trends in socioeconomic inequalities in self-assessed health (SAH) in Europe between 1990 and 2010. Data were obtained from nationally representative surveys from 17 European countries for the various years between 1990 and 2010. The age-standardised prevalence of less-than-good SAH was analysed by education and occupation among men and women aged 30-79 years. Socioeconomic inequalities were measured by means of absolute rate differences and relative rate ratios. Meta-analysis with random-effects models was used to examine the trends of inequalities. We observed declining trends in the prevalence of less-than-good SAH in many countries, particularly in Southern and Eastern Europe and the Baltic states. In all countries, less-than-good SAH was more prevalent in lower educational and manual groups. For all countries together, absolute inequalities in SAH were mostly constant, whereas relative inequalities increased. Almost no country consistently experienced a significant decline in either absolute or relative inequalities. Trends in inequalities in SAH in Europe were generally less favourable than those found for inequalities in mortality, and there was generally no correspondence between the two when we compared the trends within countries. In order to develop policies or interventions that effectively reduce inequalities in SAH, a better understanding of the causes of these inequalities is needed.


Boron Isotopes in the Puga Geothermal System, India, and Their Implications for the Habitat of Early Life.
Boron is associated with several Archean stromatolite deposits, including the tourmaline-rich Barberton stromatolites in South Africa and tourmaline-bearing pyritic laminae associated with stromatolites of the 3.48 Ga Dresser Formation in the Pilbara Craton, Australia. Boron is also a critical element in prebiotic organic chemistry, including in the formation of ribose, a crucial component in RNA. As geological evidence and advances in prebiotic chemistry are now suggesting that hot spring activity may be associated with the origins of life, an understanding of boron and its mobility and isotopic fractionation in geothermal settings may provide important insights into the setting for the origin of life. Here, we report on the boron isotopic compositions and elemental concentrations in a range of fluid, sediment, and mineral samples from the active, boron-rich Puga geothermal system in the Himalayas, India. This includes one of the lowest boron isotope values ever recorded in modern settings: diatom-rich sediments (δ11B = -41.0‰) in a multiphase fractionation system where evaporation is not the dominant form of isotope fractionation. Instead, the extreme boron isotopic fractionation is ascribed to the incorporation of tetrahedral 10B borate anions in precipitating amorphous silica. These findings expand the known limits and drivers of boron isotope fractionation, as well as provide insight into the concentration and fractionation of boron in Archean hot spring environments.


Fish consumption measured during pregnancy and risk of cardiovascular diseases later in life: an observational prospective study.
Previous studies have indicated a protective effect of long chain n-3 PUFAs against cardiovascular disease; however, the overall evidence remains uncertain, and there is a general lack of knowledge in the field of cardiovascular epidemiology in women. Therefore, the objective of this study was to explore the association between fish intake and cardiovascular disease among 7429 women from a prospective pregnancy cohort in Aarhus, Denmark, who were followed for 12-17 years. Exposure information derived from a questionnaire sent to the women in gestation week 16, and daily fish consumption was quantified based on assumptions of standard portion sizes and food tables. Information on admissions to hospital was obtained from the Danish National Patient Registry and diagnoses of hypertensive, cerebrovascular and ischaemic heart disease were used to define the outcome: cardiovascular disease. During the follow-up period 263 events of cardiovascular disease were identified. Overall, there was no association between cardiovascular disease and fish intake, confidence intervals for effect estimates in the different fish intake groups were wide, overlapped and for all but one they encompassed unity. Restricting the analysis to women who had reported the same fish intake in a questionnaire in gestation week 30 did not alter these findings. In conclusion, our data from a prospective cohort of relatively young and initially healthy women from Aarhus linked with information from registries could not substantiate a protective effect of fish intake against cardiovascular disease.


Age-specific mortality during the 1918 influenza pandemic: unravelling the mystery of high young adult mortality.
The worldwide spread of a novel influenza A (H1N1) virus in 2009 showed that influenza remains a significant health threat, even for individuals in the prime of life. This paper focuses on the unusually high young adult mortality observed during the Spanish flu pandemic of 1918. Using historical records from Canada and the U.S., we report a peak of mortality at the exact age of 28 during the pandemic and argue that this increased mortality resulted from an early life exposure to influenza during the previous Russian flu pandemic of 1889-90. We posit that in specific instances, development of immunological memory to an influenza virus strain in early life may lead to a dysregulated immune response to antigenically novel strains encountered in later life, thereby increasing the risk of death. Exposure during critical periods of development could also create holes in the T cell repertoire and impair fetal maturation in general, thereby increasing mortality from infectious diseases later in life. Knowledge of the age-pattern of susceptibility to mortality from influenza could improve crisis management during future influenza pandemics.


Evaluation of 11 years of newborn screening for maple syrup urine disease in the Netherlands and a systematic review of the literature: Strategies for optimization.
Maple syrup urine disease (MSUD) leads to severe neurological deterioration unless diagnosed early and treated immediately. We have evaluated the effectiveness of 11 years of MSUD newborn screening (NBS) in the Netherlands (screening >72 hours, referral if both total leucine (Xle) and valine ≥400 μmol/L blood) and have explored possibilities for improvement by combining our data with a systematic literature review and data from Collaborative Laboratory Integrated Reports (CLIR). Dutch MSUD NBS characteristics and accuracy were determined. The hypothetical referral numbers in the Dutch population of additional screening markers suggested by CLIR were calculated. In a systematic review, articles reporting NBS leucine concentrations of confirmed patients were included. Our data showed that NBS of 1 963 465 newborns identified 4 MSUD patients and led to 118 false-positive referrals (PPV 3.28%; incidence 1:491 000 newborns). In literature, leucine is the preferred NBS parameter. Total leucine (Xle) concentrations (mass-spectrometry) of 53 detected and 8 false-negative patients (sampling age within 25 hours in 3 patients) reported in literature ranged from 288 to 3376 (median 900) and 42 to 325 (median 209) μmol/L blood respectively. CLIR showed increasing Xle concentrations with sampling age and early NBS sampling and milder variant MSUD phenotypes with (nearly) normal biochemical profiles are causes of false-negative NBS results. We evaluated the effect of additional screening markers and established the Xle/phenylalanine ratio as a promising additional marker ratio for increasing the PPV, while maintaining high sensitivity in the Dutch MSUD NBS.


Clinical and laboratory features of in-patients with multiple sclerosis in a University Hospital in Tokyo from 1988-2002.
The aim of this study was to analyze the clinical and laboratory features of each subtype of multiple sclerosis (MS) (relapsing-remitting, primary progressive, and secondary progressive) in the Tokyo metropolitan area. We retrospectively analyzed the medical records of 104 consecutive patients with a diagnosis of MS, who had been admitted to our university hospital from 1988 to 2002. They all met criteria for definite MS, by clinical or laboratory standards. Eighty-four (80.8%) patients were classified as having relapsing-remitting MS, while 8 patients (7.7%) and 12 patients (11.5%) were classified as having primary progressive MS and secondary progressive MS, respectively. A significant female predominance existed in the relapse-remitting MS (female : male=2.4 : 1) cohort, but this ratio was 1 : 1 in both primary progressive and secondary progressive MS. The age at onset was older in the primary progressive MS (36.6+/-17.1 years of old) population than in either the relapsing-remitting MS (27.9+/-11.1) or the secondary progressive MS (27.8+/-11.5) subjects. Although the duration of illness was similar among the three types of MS, the number of exacerbations in the secondary progressive (5.9+/-4.6) cohort was significantly higher than that in the relapsing-remitting MS subjects (3.2+/-2.6). Patients with primary progressive MS showed a significantly higher rate of gait disturbance (87.5%) as the initial symptom than those with relapsing-remitting MS (23.8%), and this was thought to be due to the higher incidence of brainstem and spinal cord lesions. Visual disturbance as the initial symptom was frequently noted in those with secondary progressive MS (50.0%), while it was noted only in 29.8% and 12.5% in the relapsing-remitting and primary progressive patients, respectively. Primary progressive MS subjects had a higher propensity to be wheelchair-bound (75.0%) than those suffering from relapsing-remitting MS (1.2%). Increased total protein in the cerebrospinal fluid (CSF) of the secondary progressive cohort was statistically significant compared to the relapsing-remitting cohort. The frequency of oligoclonal IgG bands was rather low in each type of MS (17.1-33.3%). Gadolinium enhancement of plaques on MRI was more frequently present in secondary progressive MS (66.7%) than in either relapsing-remitting MS (32.1%) or primary progressive MS (50.0%). Of note, the opticospinal form was found in only 16.3% of the total MS patients, a proportion less than that in previous reports from southern Japan. The present study confirms that while the clinical and laboratory features of the MS patients in the Tokyo metropolitan area are similar to those in Western countries in most regards, features such as proportionally fewer primary and secondary progressive MS patients as well as less oligoclonal IgG bands on CSF analysis are different from those in Western countries.


Mindfulness Interventions in Physical Rehabilitation: A Scoping Review.
A scoping review was conducted to describe how mindfulness is used in physical rehabilitation, identify implications for occupational therapy practice, and guide future research on clinical mindfulness interventions. A systematic search of four literature databases produced 1,524 original abstracts, of which 16 articles were included. Although only 3 Level I or II studies were identified, the literature included suggests that mindfulness interventions are helpful for patients with musculoskeletal and chronic pain disorders and demonstrate trends toward outcome improvements for patients with neurocognitive and neuromotor disorders. Only 2 studies included an occupational therapist as the primary mindfulness provider, but all mindfulness interventions in the selected studies fit within the occupational therapy scope of practice according to the American Occupational Therapy Association's Occupational Therapy Practice Framework: Domain and Process. Higher-level research is needed to evaluate the effects of mindfulness interventions in physical rehabilitation and to determine best practices for the use of mindfulness by occupational therapy practitioners.


Sodium butyrate stimulates mineralized nodule formation and osteoprotegerin expression by human osteoblasts.
Butyric acid (sodium butyrate; BA) is a major metabolic by-product of main periodontopathic bacteria present in subgingival plaque. In the present study, we examined the effects of BA on cell proliferation, alkaline phosphatase (ALPase) activity, mineralized nodule formation, extracellular matrix protein expression, macrophage colony-stimulating factor (M-CSF), and osteoprotegerin (OPG) in normal human osteoblasts. The cells were cultured with 0, 10(-8), 10(-6) or 10(-4)M BA for up to 12 days. Mineralized nodule formation was detected by alizarin red staining, and the calcium content in mineralized nodules was determined using a calcium assay kit. The gene and protein expression levels for type I collagen, bone sialoprotein (BSP), osteopontin (OPN), M-CSF, and OPG were examined using real-time PCR and ELISA, respectively. Mineralized nodule formation and the calcium content of mineralized nodules were increased by BA in a dose-dependent manner. Cell proliferation and ALPase activity were not affected by the addition of BA. Following the addition of 10(-4)M BA, the expression levels of BSP, OPN, and OPG increased, whereas the expression levels of type I collagen and M-CSF were not markedly affected. These results suggest that BA stimulates bone formation by increasing the production of BSP and OPN, whereas it suppresses osteoclast differentiation by increasing the production of OPG by human osteoblasts.


Prolonged Mechanical Ventilation: Challenges to Nurses and Outcome in Extremely Preterm Babies.
Worldwide, about 15 million infants are born prematurely each year. Technological advances, including invasive mechanical ventilation, play a major role in the survival of extremely preterm babies. Those who survive may have prolonged morbid conditions that result in long-term sequelae. Nurses face several challenges during the hospitalization of these infants. Vigilant care, monitoring, and careful handling of the infants can prevent infections and long-term complications. Newer, less invasive technologies are promising for improved outcomes in extremely preterm infants.


Transcript Expression Data from Human Islets Links Regulatory Signals from Genome-Wide Association Studies for Type 2 Diabetes and Glycemic Traits to Their Downstream Effectors.
The intersection of genome-wide association analyses with physiological and functional data indicates that variants regulating islet gene transcription influence type 2 diabetes (T2D) predisposition and glucose homeostasis. However, the specific genes through which these regulatory variants act remain poorly characterized. We generated expression quantitative trait locus (eQTL) data in 118 human islet samples using RNA-sequencing and high-density genotyping. We identified fourteen loci at which cis-exon-eQTL signals overlapped active islet chromatin signatures and were coincident with established T2D and/or glycemic trait associations. At some, these data provide an experimental link between GWAS signals and biological candidates, such as DGKB and ADCY5. At others, the cis-signals implicate genes with no prior connection to islet biology, including WARS and ZMIZ1. At the ZMIZ1 locus, we show that perturbation of ZMIZ1 expression in human islets and beta-cells influences exocytosis and insulin secretion, highlighting a novel role for ZMIZ1 in the maintenance of glucose homeostasis. Together, these findings provide a significant advance in the mechanistic insights of T2D and glycemic trait association loci.


Neuro-Muscular Dentistry: the "diamond" concept of electro-stimulation potential for stomato-gnathic and oro-dental conditions.
Oro-Pharyngeal Dysphagia - or simply dysphagia - is the difficulty (persistent) in swallowing/passing food and/or liquid from the mouth to the pharynx into the esophagus and finally the stomach; a deglutition disorder (a symptom, by definition, often due to neuro-degenerative/-muscular, drug-induced or localized structural pathologies such as head and neck tumors, lesions and associated surgical and/or radiation injuries) linked to severe consequences on Quality of Life (QoL), including malnutrition, dehydration, and even sudden death. Likewise, Temporo-Mandibular Jaw and Joint disorder(s) - or simply TMD - is a multifactorial etiological condition, regularly encountered in the dental office. Whether due to malocclusion, bruxism, stress and/or trauma, TMD destabilizes the whole cranio-mandibular system structurally and functionally, via affecting mastication, teeth, supporting structures, comfort and aesthetics, and thus, QoL, again. While several treatment regimens do exist for such conditions, some of which have been standardized for use over the years, most continue to lack proper evidence-based literature support. Hence, (1) caution is to be exercised; and (2) the need for alternative therapeutic strategies is amplified, subsequently, the door for innovation is wide open. Indeed, neuromuscular electrical stimulation or "NMES", is perhaps a fine example. Herein, we present the interested oro-dental health care provider with an up-dated revision of this therapeutic modality, its potential benefits, risks and concerns, to best handle the dysphagic patient: an intra-disciplinary approach or strategy bridging contemporary dentistry with speech and language therapy; a rather obscure and un-discovered yet critical allied health profession. A pre-clinical and clinical prospectus on employing inventive NMES-based regimens and devices to manage TMD is also highlighted.


Employers, workers, and the future of employment-based health benefits.
EBRI'S BIANNUAL POLICY FORUM: This Issue Brief summarizes presentations at EBRI's 65th biannual policy forum, held in Washington, DC, on Dec. 10, 2009, on the topic, "Employers, Workers, and the Future of Employment-Based Health Benefits." The forum brought together a wide range of economic, benefits, management, and labor experts to share their expertise at a time when major health reform legislation was being debated in Congress. The focus: How might this affect the way that the vast majority of Americans currently get their health insurance coverage? THE EMPLOYMENT-BASED HEALTH INSURANCE SYSTEM: Most people who have health insurance coverage in the United States get it through their job: In 2008, about 61 percent of the nonelderly population had employment-based health benefits, 19 percent were covered by public programs, 6 percent had individual coverage, and 17 percent were uninsured. Not surprisingly, given the deep conflicts that exist over President Obama's health reform plan and the different bills that have passed the House and Senate, benefits experts also do not agree on what "health reform" will mean for either workers or employers. Views ranged from "Will anyone notice?" to predictions of great upheaval for workers and their employers, patients and health care providers, and the entire U.S. health care system. One point of consensus among both labor and management representatives: Imposing a tax on health benefits is likely to cause major cuts in health benefits and might result in structural changes in the employment-based benefits system. A common disappointment voiced at the forum was that the initial effort to reform the delivery and cost of health care in America gradually became focused on just financing and coverage of health insurance. The ever-rising cost of health insurance affects different employers and workers in different ways--with small employers and low-wage workers being the most disadvantaged. With health premiums having risen almost five times as much as the overall rate of inflation since 2000, employers face unsustainable cost increases in health benefits. For a minimum-wage worker, the cost of family coverage (averaging about $13,700 a year in a small firm) exceeds their total annual income (about $11,500 a year). Small employers, if they offer health benefits at all, pay proportionately more than large employers for the same health coverage. As reflected by the debate in Congress, the American public has conflicted opinions on both the U.S. health care system and on reform: Surveys find that people tend to be satisfied with the quality of their own care but not with costs and access, and a majority rates the system as fair or poor. Opinions divide sharply along partisan lines. While large employers tend to express continued commitment to health benefits, small employers see themselves strongly disadvantaged by the current system. Consultants report many employers privately want to drop benefits to control costs, but realize there are risks to doing so and none wants to be first. Employers express strong interest in wellness and disease management programs as a way to control costs, even though some experts say there is no evidence these work. Consumer-driven health plans are expected to continue their slow rate of growth.


Transgenic Soybean Production of Bioactive Human Epidermal Growth Factor (EGF).
Necrotizing enterocolitis (NEC) is a devastating condition of premature infants that results from the gut microbiome invading immature intestinal tissues. This results in a life-threatening disease that is frequently treated with the surgical removal of diseased and dead tissues. Epidermal growth factor (EGF), typically found in bodily fluids, such as amniotic fluid, salvia and mother's breast milk, is an intestinotrophic growth factor and may reduce the onset of NEC in premature infants. We have produced human EGF in soybean seeds to levels biologically relevant and demonstrated its comparable activity to commercially available EGF. Transgenic soybean seeds expressing a seed-specific codon optimized gene encoding of the human EGF protein with an added ER signal tag at the N' terminal were produced. Seven independent lines were grown to homozygous and found to accumulate a range of 6.7 +/- 3.1 to 129.0 +/- 36.7 μg EGF/g of dry soybean seed. Proteomic and immunoblot analysis indicates that the inserted EGF is the same as the human EGF protein. Phosphorylation and immunohistochemical assays on the EGF receptor in HeLa cells indicate the EGF protein produced in soybean seed is bioactive and comparable to commercially available human EGF. This work demonstrates the feasibility of using soybean seeds as a biofactory to produce therapeutic agents in a soymilk delivery platform.


Genomic Analysis of Salmonella enterica Serovar Typhimurium DT160 Associated with a 14-Year Outbreak, New Zealand, 1998-2012.
During 1998-2012, an extended outbreak of Salmonella enterica serovar Typhimurium definitive type 160 (DT160) affected >3,000 humans and killed wild birds in New Zealand. However, the relationship between DT160 within these 2 host groups and the origin of the outbreak are unknown. Whole-genome sequencing was used to compare 109 Salmonella Typhimurium DT160 isolates from sources throughout New Zealand. We provide evidence that DT160 was introduced into New Zealand around 1997 and rapidly propagated throughout the country, becoming more genetically diverse over time. The genetic heterogeneity was evenly distributed across multiple predicted functional protein groups, and we found no evidence of host group differentiation between isolates collected from human, poultry, bovid, and wild bird sources, indicating ongoing transmission between these host groups. Our findings demonstrate how a comparative genomic approach can be used to gain insight into outbreaks, disease transmission, and the evolution of a multihost pathogen after a probable point-source introduction.


Immune response to sipuleucel-T in prostate cancer.
Historically, chemotherapy has remained the most commonly utilized therapy in patients with metastatic cancers. In prostate cancer, chemotherapy has been reserved for patients whose metastatic disease becomes resistant to first line castration or androgen deprivation. While chemotherapy palliates, decreases serum prostate specific antigen and improves survival, it is associated with significant side effects and is only suitable for approximately 60% of patients with castrate-resistant prostate cancer. On that basis, exploration of other therapeutic options such as active secondary hormone therapy, bone targeted treatments and immunotherapy are important. Until recently, immunotherapy has had no role in the treatment of solid malignancies aside from renal cancer and melanoma. The FDA-approved autologous cellular immunotherapy sipuleucel-T has demonstrated efficacy in improving overall survival in patients with metastatic castrate-resistant prostate cancer in randomized clinical trials. The proposed mechanism of action is reliant on activating the patients' own antigen presenting cells (APCs) to prostatic acid phosphatase (PAP) fused with granulocyte-macrophage colony stimulating factor (GM-CSF) and subsequent triggered T-cell response to PAP on the surface of prostate cancer cells in the patients body. Despite significant prolongation of survival in Phase III trials, the challenge to health care providers remains the dissociation between objective changes in serum PSA or on imaging studies after sipleucel-T and survival benefit. On that basis there is an unmet need for markers of outcome and a quest to identify immunologic or clinical surrogates to fill this role. This review focuses on the impact of sipuleucel-T on the immune system, the T and B cells, and their responses to relevant antigens and prostate cancer. Other therapeutic modalities such as chemotherapy, corticosteroids and GM-CSF and host factors can also affect immune response. The optimal timing for immunotherapy, patient selection and best sequencing with other prostate cancer therapies remain to be determined. A better understanding of immune response may help address these issues.


Production of an insecticidal crystal protein from Bacillus thuringiensis by the methylotroph Methylobacterium extorquens.
The Cry1Aa protein from Bacillus thuringiensis is an insecticidal protein that is highly active against several species of Lepidoptera. We cloned and expressed the cry1Aa gene in a plant-colonizing methylotroph, Methylobacterium extorquens, under the control of the strong M. extorquens AM1 methanol dehydrogenase promoter, P(mxaF). Transmission electron microscopy revealed characteristic bipyramidal intracellular delta-endotoxin crystals similar to the crystalline inclusions formed by B. thuringiensis. Both the protoxin protein and the activated toxin were visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western analysis. In single-dose assays of the recombinant against the silkworm, Bombyx mori, both whole cells and cell lysates caused rapid feeding inhibition followed by mortality. The biomass and growth rate of recombinant cells in shake flask culture were similar to those of the wild-type strain, indicating a lack of fitness cost to the recombinant under controlled culture conditions. Recombinant Cry1Aa was expressed at a level of 4.5% of total M. extorquens cell protein. The potential benefits of modifying M. extorquens to deliver insecticidal Cry proteins for crop and forest protection are discussed.


Effect of changes in inspiratory flow rate on cough responses to inhaled capsaicin.
1. Twelve non-smoking subjects inhaled capsaicin at three different inspiratory flow rates: 50, 100 and 150 litres/min. Capsaicin was delivered by a breath-actuated dosimeter; inhalations consisted of 0.21-13.6 nmol of capsaicin in doubling amounts given in random order. 2. The mean number of coughs per challenge decreased with increasing inspiratory flow rate. The difference in cough numbers were significant: 7.7 (95% confidence interval 2.5-12.8) for 50 versus 100 litres/min and 10.9 (95% confidence interval 5.0-16.9) for 100 versus 150 litres/min. 3. On a separate day, a cough threshold was measured by giving increasing doses of citric acid that were inhaled at 50 litres/min. There was a positive correlation between the sensitivity to capsaicin and the cough threshold to citric acid (r = 0.69, P = 0.01), and also between the cough latencies (r = 0.67, P = 0.02). 4. The negative relationship between the cough response and the inspiratory flow rate may be caused by increased laryngeal deposition at lower inspiratory flow rates. 5. These results are compatible with a similar anatomical distribution of cough receptors for capsaicin and citric acid. 6. These results suggest that changes in inspiratory flow rate may affect the results of cough challenges.


Target-Specific Assay for Rapid and Quantitative Detection of Mycobacterium chimaera DNA.
Mycobacterium chimaera is an opportunistic environmental mycobacterium belonging to the Mycobacterium avium-M. intracellulare complex. Although most commonly associated with pulmonary disease, there has been growing awareness of invasive M. chimaera infections following cardiac surgery. Investigations suggest worldwide spread of a specific M. chimaera clone, associated with contaminated hospital heater-cooler units used during the surgery. Given the global dissemination of this clone, its potential to cause invasive disease, and the laboriousness of current culture-based diagnostic methods, there is a pressing need to develop rapid and accurate diagnostic assays specific for M. chimaera Here, we assessed 354 mycobacterial genome sequences and confirmed that M. chimaera is a phylogenetically coherent group. In silico comparisons indicated six DNA regions present only in M. chimaera We targeted one of these regions and developed a TaqMan quantitative PCR (qPCR) assay for M. chimaera with a detection limit of 100 CFU/ml in whole blood spiked with bacteria. In vitro screening against DNA extracted from 40 other mycobacterial species and 22 bacterial species from 21 diverse genera confirmed the in silico-predicted specificity for M. chimaera Screening 33 water samples from heater-cooler units with this assay highlighted the increased sensitivity of PCR compared to culture, with 15 of 23 culture-negative samples positive by M. chimaera qPCR. We have thus developed a robust molecular assay that can be readily and rapidly deployed to screen clinical and environmental specimens for M. chimaera.


Functional abnormalities in renal cystic diseases.
The functions of a kidney, whether normal or cystic, can be conceptualized in terms of anatomy (glomerulus, proximal tubule, loop of Henle, distal convolution, and collecting duct), activity (volume regulation, dilution and concentration, acid-base regulation, potassium excretion, transport of organic molecules, and calcium and phosphate excretion), and the integration of anatomic organization to meet functional demand. Our discussion of renal cystic disorders follows this conceptual outline. For discussions of normal renal physiology, the reader is referred to any one of several recent, excellent reviews (1-3). Systematic evaluation of renal function in cystic diseases of the kidney (medullary sponge kidney, medullary cystic disease, and polycystic kidney disease) has only rarely been performed. The available information suggests that the earliest detectable lesions consist primarily of tubular dysfunction. With time, however, significant reduction of glomerular filtration occurs and the resultant accumulation of uremic toxins dominates the clinical picture in polycystic and medullary cystic disease. Significant changes in glomerular function are unusual in medullary sponge kidney. This review represents an attempt to summarize the large body of literature that has accumulated on functional abnormalities in these disorders, and to point out those areas where further investigations are needed.


HIV incidence among injection drug users in New York City, 1992-1997: evidence for a declining epidemic.
We assessed recent (1992-1997) HIV incidence in the large HIV epidemic among injection drug users in New York City. Data were compiled from 10 separate studies (N = 4979), including 6 cohort studies, 2 "repeat service user" studies, and 2 analyses of voluntary HIV testing and counseling services within drug treatment programs. In the 10 studies, 52 seroconversions were found in 6344 person-years at risk. The observed incidence rates among the 10 studies were all within a narrow range, from 0 per 100 person-years at risk to 2.96 per 100 person-years at risk. In 9 of the 10 studies, the observed incidence rate was less than 2 per 100 person-years at risk. The weighted average incidence rate was 0.7 per 100 person-years at risk. The recent incidence rate in New York City is quite low for a high-seroprevalence population of injection drug users. The very large HIV epidemic among injection drug users in New York City appears to have entered a "declining phase," characterized by low incidence and declining prevalence. The data suggest that very large high-seroprevalence HIV epidemics may be "reversed."


Fimbrial phase variation and DNA rearrangements in uropathogenic isolates of Escherichia coli.
Having previously shown that the oscillating on-off expression (phase variation) of type 1 fimbriae in Escherichia coli is regulated genetically by an invertible element of DNA, we wished to determine whether E. coli isolates recovered from infected humans behaved in similar fashion. We examined four different clinical isolates that expressed type 1 fimbriae, P fimbriae, or both. Using, in Southern blot analysis, a DNA probe from the type 1 fimbrial switch, that hybridized to one DNA band from phase-on bacteria and to two DNA bands from phase-off bacteria, we found that the three clinical isolates expressing type 1 fimbriae contained the same invertible switch previously seen in the K-12 isolate. Employing a similar approach to characterize the on-off expression of P fimbriae, we used a DNA probe containing the known transcriptional signals for P fimbriae. Although we detected DNA rearrangement in the two strains expressing P fimbriae, unlike the case for type 1 fimbriae, the rearrangement did not correlate with the on-off state of the P fimbriae. Rather, the DNA rearrangement correlated with the environmental conditions of growth of the bacteria from which the DNA was isolated. These results confirm the notion that P fimbriae expression and type 1 fimbriae expression are controlled differently.


Bacterial cGAS-like enzymes synthesize diverse nucleotide signals.
Cyclic dinucleotides (CDNs) have central roles in bacterial homeostasis and virulence by acting as nucleotide second messengers. Bacterial CDNs also elicit immune responses during infection when they are detected by pattern-recognition receptors in animal cells. Here we perform a systematic biochemical screen for bacterial signalling nucleotides and discover a large family of cGAS/DncV-like nucleotidyltransferases (CD-NTases) that use both purine and pyrimidine nucleotides to synthesize a diverse range of CDNs. A series of crystal structures establish CD-NTases as a structurally conserved family and reveal key contacts in the enzyme active-site lid that direct purine or pyrimidine selection. CD-NTase products are not restricted to CDNs and also include an unexpected class of cyclic trinucleotide compounds. Biochemical and cellular analyses of CD-NTase signalling nucleotides demonstrate that these cyclic di- and trinucleotides activate distinct host receptors and thus may modulate the interaction of both pathogens and commensal microbiota with their animal and plant hosts.


Contracting for clinical genetic services: the Welsh model.
In a time of increasing competition for clinical services resources, it is imperative that health professionals actively participate in the commissioning process in order to ensure that established clinical standards are not compromised. Introduction of the NHS reforms in the UK in the early 1990s highlighted the difficulties in contracting for a specialised service such as clinical genetics, especially in the absence of a consensus regarding the contract currency. An average block contract price for each new family referred was introduced in Wales in 1992, and data from the subsequent five years show that this charging system is economically feasible and has the advantages of (1) recognising the contribution to care of non-medical personnel on the genetics team, (2) covering follow up including the counselling of relatives, (3) protecting the service from loss of income owing to non-attendance, and (4) providing a basis for negotiation when new services are being proposed to purchasers. Activity data show that while the majority of conditions incur below average cost, the mean cost is influenced by a small number of autosomal dominant and X linked disorders. The cost risk to the provider for seeing families over an extended period is minimal, as the data establish that family files experience an exponential decrease in activation probability over the early years, but this becomes constant later on. The robustness of the system is dependent on accurate baseline data on referral patterns to the service, recording of activity, and staff costs.


Multisensory approach to handwriting remediation: perceptions of school-based occupational therapists.
The purpose of this study was to describe the current practices of school-based occupational therapists regarding their use of multisensory modalities and activities in handwriting remediation. A survey was sent to 313 school-based occupational therapist members of the American Occupational Therapy Association who identified themselves as working in a school system as their primary employment setting. Of these, 198 surveys were returned and analyzed descriptively, resulting in a response rate of 63.3%. More than 130 different multisensory modalities and activities were documented. Twenty-five of these had previously been reported in the literature, the other 114 were documented, by respondents, within the "other" category. Most respondents reported using 5 or more modalities and activities per student, the most frequent being chalk and chalkboard. No consensus among respondents is apparent about the primary sensory systems stimulated by the modalities and activities. No difference in modality and activity use was found on the basis of demographic variables. Overall findings indicate that the breadth of modalities and activities being used is far greater than that currently found in the literature. The results suggest a need for completing studies designed to examine the use and effectiveness of multisensory modalities and activities in handwriting remediation.


Transmission between pairs of hippocampal slice neurons: quantal levels, oscillations, and LTP.
Long-term potentiation (LTP) of synaptic transmission after coincident pre- and postsynaptic activity is considered a cellular model of changes underlying learning and memory. In intact tissue, LTP has been observed only between populations of neurons, making analysis of mechanisms difficult. Transmission between individual pre- and postsynaptic hippocampal cells was studied, suggesting quantal amplitude distributions with little variability in quantal size. LTP between such pairs is manifested by large, persistent, and synapse-specific potentiation with a shift in amplitude distribution that suggests presynaptic changes. Oscillations in amplitude of transmission, apparently of presynaptic origin, are common and can be triggered by LTP.


Parental military service, agent orange exposure, and the risk of rhabdomyosarcoma in offspring.
To evaluate the role of parental military service-related exposures and rhabdomyosarcoma (RMS) risk in offspring using data from a large case-control study of childhood RMS. Cases (n = 319) were enrolled from the third trial run by the Intergroup Rhabdomyosarcoma Study Group. Population-based controls (n = 319) were pair-matched to cases on race, sex, and age. Conditional logistic regression was used to evaluate parental military service-related exposures and their associations with childhood RMS by generating aORs and 95% CIs. Statistical significance was defined as P < .05. There were no significant associations between parental military service and childhood RMS. The strongest association was with maternal military service; however, this association was attenuated and did not remain significant after adjusting for covariates (aOR = 2.75, 95% CI 0.71, 10.62). An elevated effect estimate was found when assessing paternal exposure to Agent Orange (AO) and childhood RMS but was not statistically significant (aOR = 1.72, 95% CI 0.55, 5.41). We found little evidence that parental military service of AO exposure influences the risk of RMS in offspring. These findings are notable in light of the continuing controversies surrounding the intergenerational effects of AO exposure.


TinyONet: A Cache-Based Sensor Network Bridge Enabling Sensing Data Reusability and Customized Wireless Sensor Network Services.
In recent years, a few protocol bridge research projects have been announced to enable a seamless integration of Wireless Sensor Networks (WSNs) with the TCP/IP network. These studies have ensured the transparent end-to-end communication between two network sides in the node-centric manner. Researchers expect this integration will trigger the development of various application domains. However, prior research projects have not fully explored some essential features for WSNs, especially the reusability of sensing data and the data-centric communication. To resolve these issues, we suggested a new protocol bridge system named TinyONet. In TinyONet, virtual sensors play roles as virtual counterparts of physical sensors and they dynamically group to make a functional entity, Slice. Instead of direct interaction with individual physical sensors, each sensor application uses its own WSN service provided by Slices. If a new kind of service is required in TinyONet, the corresponding function can be dynamically added at runtime. Beside the data-centric communication, it also supports the node-centric communication and the synchronous access. In order to show the effectiveness of the system, we implemented TinyONet on an embedded Linux machine and evaluated it with several experimental scenarios.


Expression QTL (eQTLs) Analyses Reveal Candidate Genes Associated With Fruit Flesh Softening Rate in Peach [Prunus persica (L.) Batsch].
Significant differences in softening rate have been reported between melting flesh in peach and nectarine varieties. This trait seems to be controlled by several genes. We aimed to identify candidate genes involved in fruit softening rate by integrating quantitative trait loci (QTL) and expression QTL (eQTL) analyses, comparing siblings with contrasting softening rates. We used a segregating population derived from nectarine cv. 'Venus' selfing, which was phenotyped for softening rate during three seasons. Six siblings with high (HSR) and six with low softening rate (LSR) were sequenced using RNA-Seq. A group of 5,041 differentially expressed genes was identified. Also, we found a QTL with a LOD (logarithm of odds) score of 9.7 on LG4 in all analyzed seasons. Furthermore, we detected 1,062 eQTLs, of which 133 were found co-localizing with the identified QTL. Gene Ontology (GO) analysis showed 'Response to auxin' as one the main over-represented categories. Our findings suggest over-expression of auxin biosynthetic related genes in the HSR group, which implies a higher expression and/or accumulation of auxin, thereby triggering fast softening. Conversely, the LSR phenotype might be explained by an altered auxin-homeostasis associated with low auxin levels. This work will contribute to unraveling the genetic mechanisms responsible for the softening rate in peaches and nectarines and lead to the development of molecular markers.


Temporal power spectra of irradiance scintillation for infrared optical waves' propagation through marine atmospheric turbulence.
Current theoretical temporal power spectra models of an optical wave have been developed for terrestrial environments. The interactions between humidity and temperature fluctuations in the marine atmospheric environments make the marine atmospheric turbulence particularly challenging, and the optical waves' propagation through marine turbulence exhibits a different behavior with respect to terrestrial propagation. In this paper, the temporal power spectra of irradiance scintillation under weak marine atmospheric turbulence, which is one of the key temporal statistics to describe the correlation of irradiance fluctuations at different time instances, is investigated in detail both analytically and numerically. Closed-form expressions for the temporal power spectra of irradiance scintillation are derived for infrared plane and spherical waves under weak marine atmospheric turbulence, and they consider physically the influences of finite turbulence inner and outer scales. The final results indicate that the marine atmospheric turbulence brings more effects on the irradiance scintillation than the terrestrial atmospheric turbulence.


Expression of RANKL in osteolytic membranes: association with fibroblastic cell markers.
Aseptic loosening is often mentioned as the primary reason for costly revision of total joint arthroplasties. Receptor activator of nuclear factor-kappaB ligand (RANKL) appears to be a major factor in the bone resorption observed in periprosthetic osteolysis. RANKL plays an essential role in the recruitment, differentiation, and survival of the osteoclasts implicated in periprosthetic osteolysis. This study was performed in an effort to identify the cell type in the periprosthetic membrane responsible for expression of RANKL. Tissues harvested from osteolytic lesions in nine patients undergoing total joint revision were serially sectioned for immunohistochemical analysis. Intercellular adhesion molecule-1 (ICAM-1) and prolyl 4-hydroxylase (5B5) antibodies were used to detect fibroblasts, and anti-CD-163 (Ber-MAC3) was used to detect macrophages. In addition, antibodies to osteoprotegerin (OPG), RANKL, and receptor activator of nuclear factor-kappaB (RANK) were utilized. The binding pattern of these antibodies was then viewed with confocal microscopy with the use of only secondary antibodies as method controls. Histological analysis was confined to areas of the membrane where cells were detected with use of Hoechst 34580 nuclear stain. In the membrane specimens from all nine patients, diffuse RANKL staining was localized to areas lacking cells and more intense staining was seen in areas containing nucleated cells. There was strong colocalization between RANKL and OPG, and there was weak but specific colocalization between RANKL and both 5B5 and ICAM-1. In contrast, there was complete separation of antibody staining of Ber-MAC3 and RANKL, indicating only generalized overlap of the myeloid markers with the RANKL. RANKL expression was localized to cells that stained positively for fibroblast markers. The data also indicated that there is an intact RANKL/RANK/OPG system in the periprosthetic membrane that could regulate focalized bone resorption in osteolysis. Identifying the cell types responsible for RANKL production is critical to the development of a strategy to prevent periprosthetic osteolysis.


Development of the liver in the chicken embryo. I. Hepatic cords and sinusoids.
Hemopoiesis in the liver of the chicken embryo begins on day 7 of incubation (Hamburger and Hamilton Stage 30) and peaks on day 14 (Stage 40). During this time frame, the differentiation of hepatic cells was examined by light microscopy, transmission and scanning electron microscopy, and morphometry. The avian liver is a closely packed mass of dendriform cords and discontinuous sinusoids. Hepatocytes are pyramidal in shape, and they ring the bile canaliculi which run through the centers of the cords. Semithin sections, made possible by infiltration and embedding in glycol methacrylate, were stained with hematoxylin and eosin to assess the general architecture of the organ and the lipid content of the hepatocytes and by the periodic acid-Schiff reaction and hematoxylin to visualize the cytoplasmic stores of glycogen. The number of hepatocytes with demonstrable glycogen fluctuates erratically in early hemopoiesis, and the proportion of glycogen-containing cells progressively increases as hemopoiesis climbs to a peak. Most differentiating hepatocytes are devoid of lipid droplets until Stages 39 and 40. From Stage 30 to 35, hepatocyte volume falls to its lowest value. Subsequently (Stages 36 to 40), cell volume increases and hepatocytes achieve a relatively uniform size. Ultrastructural changes in the differentiating hepatocytes, including alterations to the mitochondria, endoplasmic reticulum, and Golgi apparatus, are documented. These morphological and morphometric findings on the prehepatocyte population and hepatic vasculature cover 2 of the 3 elements deemed critical to hepatic hemopoiesis in many vertebrates.


Reliability of health-related quality-of-life assessments made by older adults and significant others for health states of increasing cognitive impairment.
Older adults are encouraged by many organizations to engage in advance care planning in the event of decisional incapacity. Planning for future health care often involves anticipating health-related quality of life (HRQoL) in states of reduced cognitive functioning. No study has yet examined whether anticipated HRQoL is stable over time. The accuracy with which significant others can predict how an older adult envisions HRQoL in a future state of cognitive impairment is also unknown. We investigated the extent to which health-related quality-of-life ratings made by older adults and designated proxies for health states of increasing cognitive impairment are consistent over time and agree with each other. Results are based on HRQoL ratings made on a 5-point Likert scale by 235 community-based elder-proxy dyads on three occasions. Ratings were obtained for the older adult's current health state as well as under the assumption that he/she had a mild to moderate stroke, incurable brain cancer or severe dementia. Data were analyzed using both traditional approaches (e.g., intraclass correlation coefficients, Bland-Altman plots) and the theory of generalizability. We found ratings to be reasonably consistent over time and in good agreement within dyads, even more so as implied cognitive functioning worsened. Across health states, ratings over time or within elder-proxy dyads were no more than one category apart in over 87% of cases. Using the theory of generalizability, we further found that, of the two facets investigated, rater had a greater influence on score variability than occasion. These findings underscore the importance of discussing health-related quality-of-life issues during advance care planning and involving designated proxies in the discussion to enhance their understanding of the role that HRQoL should play in actual decision-making situations. Medical decision-making may be influenced by healthcare providers' and family members' assessments of an incapacitated patient's health-related quality of life, in addition to that of the designated proxy. Future studies should investigate whether these two groups of individuals share the views of the patient and the designated proxy on anticipated HRQoL.


The influence of academic discourses on medical students' identification with the discipline of family medicine.
To understand the influence of academic discourses about family medicine on medical students' professional identity construction during undergraduate training. The authors used a multiple case study research design involving international medical schools, one each from Canada, France, Spain, and the United Kingdom (UK). The authors completed the fieldwork between 2007 and 2009 by conducting 18 focus groups (with 132 students) and 67 semistructured interviews with educators and by gathering pertinent institutional documents. They carried out discursive thematic analyses of the verbatim transcripts and then performed within- and cross-case analyses. The most striking finding was the diverging responses between those at the UK school and those at the other schools. In the UK case, family medicine was recognized as a prestigious academic discipline; students and faculty praised the knowledge and skills of family physicians, and students more often indicated their intent to pursue family medicine. In the other cases, family medicine was not well regarded by students or faculty. This was expressed overtly or through a paradoxical academic discourse that stressed the importance of family medicine to the health care system while decrying its lack of innovative technology and the large workload-to-income ratio. Students at these schools were less likely to consider family medicine. These results stress the influence of academic discourses on medical students' ability to identify with the practice of family medicine. Educators must consider processes of professional identity formation during undergraduate medical training as they develop and reform medical education.


High-sensitivity cardiac troponin T in prediction and diagnosis of myocardial infarction and long-term mortality after noncardiac surgery.
Perioperative myocardial infarction (MI) is a serious complication after noncardiac surgery. We hypothesized that preoperative cardiac troponin T detected with a novel high-sensitivity (hs-cTnT) assay will identify patients at risk for acute MI and long-term mortality after major noncardiac surgery. This was a prospective cohort study within the VINO trial (n = 608). Patients had been diagnosed with or had multiple risk factors for coronary artery disease and underwent major noncardiac surgery. Cardiac troponin I (contemporary assay) and troponin T (high-sensitivity assay) and 12-lead electrocardiograms were obtained before and immediately after surgery and on postoperative days 1, 2, and 3. At baseline before surgery, 599 patients (98.5%) had a detectable hs-cTnT concentration, and 247 (41%) were >14 ng/L (99th percentile). After surgery, 497 patients (82%) had a rise in hs-cTnT (median change in hs-cTnT +2.7 ng/L [interquartile range 0.7-6.8]). During the first 3 postoperative days, there were 9 patients (2.5%) with a preoperative hs-cTnT <14 ng/L with acute MI, compared with 21 patients (8.6%) with a preoperative hs-cTnT >14 ng/L (odds ratio 3.67, 95% CI 1.65-8.15). During long-term follow-up, 80 deaths occurred. The 3-year mortality rate was 11% in patients with a preoperative hs-cTnT concentration <14 ng/L compared with 25% in patients with a preoperative hs-cTnT >14 ng/L (adjusted hazard ratio 2.17, 95% CI 1.19-3.96). In this cohort of high-risk patients, preoperative hs-cTnT concentrations were significantly associated with postoperative MI and long-term mortality after noncardiac surgery.


The association between type of conception through medically assisted reproduction and childhood cognition: a Danish population-wide cohort study.
Previous research has indicated that children conceived through medically assisted reproduction (MAR) generally have cognitive outcomes comparable to or better than naturally conceived children. However, previous studies have been limited in their ability to examine this relationship at a population level and consider variations across different types of MAR. This study utilizes data from all live births in Denmark between 2006 and 2009 (n = 259 608), including a subset of births resulting from MAR conceptions (n = 13 566). The dependent variable is the standardized test scores obtained in the second and third grades of primary schools. A comparison is made between the test scores of children spontaneously conceived (SC) and those conceived through intrauterine insemination (IUI) and assisted reproductive technologies (ART). Ordinary least squares regressions are employed, with a baseline model adjusted only for birth year, as well as models that additionally account for conception-related confounders and sociodemographic family characteristics. In the baseline analysis, ART- and IUI-conceived children displayed better test scores compared with their SC peers. However, after adjusting for relevant factors, ART-conceived children performed worse than SC peers, while IUI-conceived children performed equally well as SC peers and better than ART-conceived children. These results likely reflect differences in the selection process of potential parents into the type of MAR, as well as the consequences of variations in fecundability. Nevertheless, the differences observed across conception types were overshadowed by test score disparities in socioeconomic background.


A roadmap for the synthesis of separation networks for the recovery of bio-based chemicals: Matching biological and process feasibility.
Microbial conversion of renewable feedstocks to high-value chemicals is an attractive alternative to current petrochemical processes because it offers the potential to reduce net CO2 emissions and integrate with bioremediation objectives. Microbes have been genetically engineered to produce a growing number of high-value chemicals in sufficient titer, rate, and yield from renewable feedstocks. However, high-yield bioconversion is only one aspect of an economically viable process. Separation of biologically synthesized chemicals from process streams is a major challenge that can contribute to >70% of the total production costs. Thus, process feasibility is dependent upon the efficient selection of separation technologies. This selection is dependent on upstream processing or biological parameters, such as microbial species, product titer and yield, and localization. Our goal is to present a roadmap for selection of appropriate technologies and generation of separation schemes for efficient recovery of bio-based chemicals by utilizing information from upstream processing, separation science and commercial requirements. To achieve this, we use a separation system comprising of three stages: (I) cell and product isolation, (II) product concentration, and (III) product purification and refinement. In each stage, we review the technology alternatives available for different tasks in terms of separation principles, important operating conditions, performance parameters, advantages and disadvantages. We generate separation schemes based on product localization and its solubility in water, the two most distinguishing properties. Subsequently, we present ideas for simplification of these schemes based on additional properties, such as physical state, density, volatility, and intended use. This simplification selectively narrows down the technology options and can be used for systematic process synthesis and optimal recovery of bio-based chemicals.


Annotation and classification of the bovine T cell receptor delta genes.
gammadelta T cells differ from alphabeta T cells with regard to the types of antigen with which their T cell receptors interact; gammadelta T cell antigens are not necessarily peptides nor are they presented on MHC. Cattle are considered a "gammadelta T cell high" species indicating they have an increased proportion of gammadelta T cells in circulation relative to that in "gammadelta T cell low" species such as humans and mice. Prior to the onset of the studies described here, there was limited information regarding the genes that code for the T cell receptor delta chains of this gammadelta T cell high species. By annotating the bovine (Bos taurus) genome Btau_3.1 assembly the presence of 56 distinct T cell receptor delta (TRD) variable (V) genes were found, 52 of which belong to the TRDV1 subgroup and were co-mingled with the T cell receptor alpha variable (TRAV) genes. In addition, two genes belonging to the TRDV2 subgroup and single TRDV3 and TRDV4 genes were found. We confirmed the presence of five diversity (D) genes, three junctional (J) genes and a single constant (C) gene and describe the organization of the TRD locus. The TRDV4 gene is found downstream of the C gene and in an inverted orientation of transcription, consistent with its orthologs in humans and mice. cDNA evidence was assessed to validate expression of the variable genes and showed that one to five D genes could be incorporated into a single transcript. Finally, we grouped the bovine and ovine TRDV1 genes into sets based on their relatedness. The bovine genome contains a large and diverse repertoire of TRD genes when compared to the genomes of "gammadelta T cell low" species. This suggests that in cattle gammadelta T cells play a more important role in immune function since they would be predicted to bind a greater variety of antigens.


Marking histone H3 variants: how, when and why?
DNA in eukaryotic cells is compacted into chromatin, a regular repeated structure in which the nucleosome represents the basic unit. The nucleosome not only serves to compact the genetic material but also provides information that affects nuclear functions including DNA replication, repair and transcription. This information is conveyed through numerous combinations of histone post-translational modifications (PTMs) and histone variants. A recent challenge has been to understand how and when these combinations of PTMs are imposed and to what extent they are determined by the choice of a specific histone variant. Here we focus on histone H3 variants and the PTMs that they carry before and after their assembly into chromatin. We review and discuss recent knowledge about how the choice and initial modifications of a specific variant might affect PTM states and eventually the final epigenetic state of a chromosomal domain.


Longitudinal investigation of the role of temperament and stressful life events in childhood anxiety.
The current study investigated the longitudinal relationships among behavioral inhibition (BI), life events, and anxiety in a sample of 102 BI children and 100 behaviorally uninhibited (BUI) children aged 3 to 4 years. Children's parents completed questionnaires on BI, stressful life events, and anxiety symptoms, and were administered a diagnostic interview three times in a 5-year period. In line with our hypotheses, negative life events, particularly negative behavior-dependent life events (i.e., life events that are related to the children's own behaviors), and the impact of negative life events were predictive of increases in subsequent anxiety symptoms, the likelihood of having an anxiety disorder, and increased number of anxiety diagnoses over the 5-year follow-up period. Experiencing more positive, behavior-independent life events decreased the risk of being diagnosed with an anxiety disorder. Furthermore, differences were found in life events between BI and BUI children. That is, BI children experienced fewer positive and specifically positive behavior-dependent life events, and the impact of these positive life events was also lower in BI children than in BUI children. However, BI did not interact with life events in the prediction of anxiety problems as hypothesized. Therefore, this study seems to indicate that BI and life events act as additive risk factors in the development of anxiety problems.


Targeted gene disruption in Koji mold Aspergillus oryzae.
Filamentous fungi have received attentions as hosts for heterologous protein production because of their high secretion capability and eukaryotic post-translational modifications. One of the safest hosts for heterologous protein production is Koji mold Aspergillus oryzae since it has been used in the production of Japanese fermented foods for over 1,000 years. The production levels of proteins from higher eukaryotes are much lower than those of homologous (fungal) proteins. Bottlenecks in the heterologous protein production are suggested to be proteolytic degradation of the produced protein in the medium and the secretory pathway. For construction of excellent host strains, many genes causing the bottlenecks should be disrupted rapidly and efficiently. We developed a marker recycling system with the highly efficient gene-targeting background in A. oryzae. By employing this technique, we performed multiple gene disruption of the ten protease genes. The decuple protease gene disruptant showed fourfold production level of a heterologous protein compared with the wild-type strain.


Parvalbumin basket cell myelination accumulates axonal mitochondria to internodes.
Parvalbumin-expressing (PV+) basket cells are fast-spiking inhibitory interneurons that exert critical control over local circuit activity and oscillations. PV+ axons are often myelinated, but the electrical and metabolic roles of interneuron myelination remain poorly understood. Here, we developed viral constructs allowing cell type-specific investigation of mitochondria with genetically encoded fluorescent probes. Single-cell reconstructions revealed that mitochondria selectively cluster to myelinated segments of PV+ basket cells, confirmed by analyses of a high-resolution electron microscopy dataset. In contrast to the increased mitochondrial densities in excitatory axons cuprizone-induced demyelination abolished mitochondrial clustering in PV+ axons. Furthermore, with genetic deletion of myelin basic protein the mitochondrial clustering was still observed at internodes wrapped by noncompacted myelin, indicating that compaction is dispensable. Finally, two-photon imaging of action potential-evoked calcium (Ca2+) responses showed that interneuron myelination attenuates both the cytosolic and mitochondrial Ca2+ transients. These findings suggest that oligodendrocyte ensheathment of PV+ axons assembles mitochondria to branch selectively fine-tune metabolic demands.


The Effect of Whole-Body Vibration on Subsequent Sprint Performance in Well-Trained Cyclists.
Postactivation-potentiation exercise with added whole-body vibration (WBV) has been suggested as a potential way to acutely improve sprint performance. In cycling, there are many competitions and situations where sprinting abilities are important. To investigate the effect of adding WBV to warm-up procedures on subsequent cycle sprint performance. Eleven well-trained cyclists participated in the study. All cyclists performed a familiarization session before 2 separate test sessions in randomized order. Each session included a standardized warm-up followed by 1 of the following preconditioning exercises: 30 s of half-squats without WBV or 30 s of half-squats with WBV at 40 Hz. A 15-s Wingate sprint was performed 1 min after the preconditioning exercise. Performing preconditioning exercise with WBV at 40 Hz resulted in superior peak power output compared with preconditioning exercise without WBV (1413 ± 257 W vs 1353 ± 213 W, P = .04) and a tendency toward superior mean power output during a 15-second all-out sprint (850 ± 119 W vs 828 ± 101 W, P = .08). Effect sizes showed a moderate practical effect of WBV vs no WBV on both peak and mean power output. Preconditioning exercise performed with WBV at 40 Hz seems to have a positive effect on cycling sprint performance in young well-trained cyclists. This suggests that athletes can incorporate body-loaded squats with WBV in preparations to specific sprint training to improve the quality of the sprint training and also to improve sprint performance in relevant competitions.


The Proview phosphene tonometer fails to measure ocular pressure accurately in clinical practice.
To evaluate the Proview Eye Pressure Monitor as a medical instrument and as a technique for enabling a patient to obtain an accurate measure of his or her intraocular pressure (IOP). An experimental laboratory evaluation and an independent prospective clinical study to test the reproducibility and accuracy of the Proview technique relative to Goldmann applanation tonometry. For the laboratory study, we analyzed 3 tonometers, each packaged as a Proview Eye Pressure Monitor by Bausch & Lomb. In the independent prospective experimental study, 137 subjects participated, consisting of healthy volunteers and glaucoma patients. For laboratory testing, we held each tonometer with a micrometer to assure controlled positioning and pressed its sensing tip against a force meter that produced a calibrated, digital force reading. For clinical testing, we taught subjects (n = 137) to use the Proview technique in accordance with the manufacturer's instructions. Each subject obtained 5 measurements with each of the 5 different Proview devices. A clinician measured the IOP using Goldmann applanation tonometry. We measured the absolute value, linearity, and repeatability of the force meter readings on the tonometers during the instrument laboratory evaluation. The accuracy was evaluated by comparing the Proview measurements to the Goldmann applanation measurements. Reproducibility of clinical Proview measurements was also measured. All measurements were in mmHg during the clinical evaluation. Laboratory: There was a linear relationship between the pressures read by the Proview tonometers and known forces. The Proview tonometers read the maximum pressure applied. Clinical: The Proview technique is simple to use because it was comfortable and reproducible, with an average variance of the measurements by the same patient of 3.4 mmHg(2). Other variables besides IOP seem to affect the Proview pressure measurements, as seen in the large scatter in our data, measured by our correlation coefficient of r = 0.41. The sensitivity of the Proview technique to detect patients with high IOP (which we defined as a Goldmann pressure of >/=22 mmHg) is low; the Proview pressure identified only 18% (4/22) of these patients. The Proview instrument and technique were reproducible. However, the Proview tonometer seems not to be reliable as an indicator of IOP. The sensitivity for detecting high IOP was low in this cohort, and the agreement with Goldmann applanation was poor for some individuals. This brings into question the underlying assumption that a force proportional to the IOP generates phosphenes.


GPC light shaper for speckle-free one- and two-photon contiguous pattern excitation.
Generalized Phase Contrast (GPC) is an efficient method for generating speckle-free contiguous optical distributions useful in diverse applications such as static beam shaping, optical manipulation and recently, for excitation in two-photon optogenetics. To fully utilize typical Gaussian lasers in such applications, we analytically derive conditions for photon efficient light shaping with GPC. When combined with the conditions for optimal contrast developed in previous works, our analysis further simplifies GPC's implementation. The results of our analysis are applied to practical illumination shapes, such as a circle and different rectangles commonly used in industrial or commercial applications. We also show simple and efficient beam shaping of arbitrary shapes geared towards biophotonics research and other contemporary applications. Optimized GPC configurations consistently give ~84% efficiency and ~3x intensity gain. Assessment of the energy savings when comparing to conventional amplitude masking show that ~93% of typical energy losses are saved with optimized GPC configurations.


Propensity-matched mortality comparison of incident hemodialysis and peritoneal dialysis patients.
Contemporary comparisons of mortality in matched hemodialysis and peritoneal dialysis patients are lacking. We aimed to compare survival of incident hemodialysis and peritoneal dialysis patients by intention-to-treat analysis in a matched-pair cohort and in subsets defined by age, cardiovascular disease, and diabetes. We matched 6337 patient pairs from a retrospective cohort of 98,875 adults who initiated dialysis in 2003 in the United States. In the primary intention-to-treat analysis of survival from day 0, cumulative survival was higher for peritoneal dialysis patients than for hemodialysis patients (hazard ratio 0.92; 95% CI 0.86 to 1.00, P = 0.04). Cumulative survival probabilities for peritoneal dialysis versus hemodialysis were 85.8% versus 80.7% (P < 0.01), 71.1% versus 68.0% (P < 0.01), 58.1% versus 56.7% (P = 0.25), and 48.4% versus 47.3% (P = 0.50) at 12, 24, 36, and 48 months, respectively. Peritoneal dialysis was associated with improved survival compared with hemodialysis among subgroups with age <65 years, no cardiovascular disease, and no diabetes. In a sensitivity analysis of survival from 90 days after initiation, we did not detect a difference in survival between modalities overall (hazard ratio 1.05; 95% CI 0.96 to 1.16), but hemodialysis was associated with improved survival among subgroups with cardiovascular disease and diabetes. In conclusion, despite hazard ratio heterogeneity across patient subgroups and nonconstant hazard ratios during the follow-up period, the overall intention-to-treat mortality risk after dialysis initiation was 8% lower for peritoneal dialysis than for matched hemodialysis patients. These data suggest that increased use of peritoneal dialysis may benefit incident ESRD patients.


Generation and verification of QFix kVue Calypso-compatible couch top model for a dedicated stereotactic linear accelerator with FFF beams.
This study details the generation, verification, and implementation of a treatment planning system (TPS) couch top model for patient support system used in conjunction with a dedicated stereotactic linear accelerator. Couch top model was created within the TPS using CT simulation images of the kVue Calpyso-compatible couchtop (with rails). Verification measurements were compared to TPS dose prediction for different energies (6 MV FFF and 10 MV FFF) and rail configurations (rails in and rails out) using: 1) central axis point-dose measurements with pinpoint chamber in water-equivalent phantom at 42 gantry angles for various field sizes (2 × 2 cm², 4 × 4 cm², 10 × 10 cm²); and 2) Gafchromic EBT3 film parallel to beam in acrylic slab to assess changes in surface and percent depth doses in PA geometry. To assess sensitivity of delivered dose to variations in patient lateral position, measurements at central axis using the pinpoint chamber geometry were taken at lateral couch displacements of 2, 5, and 10 mm for 6 MV FFF. The maximum percent difference for point-dose measurements was 3.24% (6 MV FFF) and 2.30% (10 MV FFF). The average percent difference for point-dose measurements was less than 1.10% for all beam energies and rail geometries. The maximum percent difference between calculated and measured dose can be as large as 13.0% if no couch model is used for dose calculation. The presence of the couch structures also impacts surface dose and PDD, which was evaluated with Gafchromic film measurements. The upstream shift in the depth of dose maximum (dmax) was found to be 10.5 mm for 6 MV FFF and 5.5 mm for 10 MV FFF for 'Rails In' configuration. Transmission of the treatment beam through the couch results in an increase in surface dose (absolute percentage) of approximately 50% for both photon energies (6 MV FFF and 10MV FFF). The largest sensitivity to lateral shifts occurred at the lateral boundary of the rail structures. The mean magnitude (standard deviation) of the deviation between shifted and centered measurements over all field sizes tested was 0.61% (0.61%) for 2 mm shifts, 0.46% (0.67%) for 5 mm shifts, and 0.86% (1.46%) for 10 mm shifts.


Interaction between mitsugumin 29 and TRPC3 participates in regulating Ca(2+) transients in skeletal muscle.
Mitsugumin 29 (MG29) is related to the fatigue and aging processes of skeletal muscle. To examine the roles of MG29 in conjunction with its binding protein, the canonical-type transient receptor potential cation channel 3 (TRPC3), in skeletal muscle, the binding region of MG29 to TRPC3 was studied along with the functional relevance of the binding in mouse primary skeletal myotubes using co-immunoprecipitation assays and Ca(2+) imaging experiments. The N-terminus and the I-II loop of MG29 constitute the binding region for TRPC3. The myotubes that expressed the MG29 mutant missing the entire TRPC3-binding region showed a disrupted binding between endogenous MG29 and TRPC3 and a reduction in Ca(2+) transients in response to membrane depolarization without affecting ryanodine receptor 1 activity, the resting cytosolic Ca(2+) level, and the amount of releasable Ca(2+) from the sarcoplasmic reticulum. Among the proteins mediating Ca(2+) movements in skeletal muscle, TRPC4 expression was significantly decreased by the MG29 mutant. Therefore, MG29 could be a new factor for regulating Ca(2+) transients during skeletal muscle contraction possibly via a correlation with TRPC3 and TRPC4.


Screening aortic drug treatments through arterial compliance measurements.
Abdominal aortic aneurysm (AAA) is a common and deadly problem. The aortic diameter increases in association with a complex remodeling process that includes changes in the structure and content of key proteins, elastin and collagen. As these changes occur, the tissue mechanical properties also change. The natural history of AAA is progressive enlargement to a point of mechanical tissue failure typically followed by death. Currently, the marker used to predict the risk of impending rupture is the largest transverse diameter. After reaching a diameter threshold of 5.5 cm the AAA needs to be surgically repaired. This criterion does not consider any patient-specific information or heterogeneity of the AAA that may, in some cases, lead to rupture before the AAA reaches the standard intervention threshold. Conversely, in many patients, continued observation beyond this threshold is safe. While no medical treatment is yet approved, doxycycline (Doxy) has been shown to greatly reduce AAA growth in animal models and has been shown to slow growth in 1 small clinical trial. While larger prospective randomized trials are needed, one unknown is what effect Doxy has on the structural integrity of the aortic wall. That is, does slowed AAA growth, by Doxy treatment, prevent rupture, or does the wall continue to weaken and the AAA instead ruptures at a smaller diameter? Using an established animal model of AAA, we begun to determine the changes in tissue mechanics compliance of the aorta as the AAA develops. Our current research is focused on verifying that these changes mimic the observed changes seen in the human population as reported by other researchers, so that we can confidently study how potential drug therapies may affect wall strength and compliance in the human population. The long-term objectives are to understand better factors related to progression of AAA and help verify that drug therapy with Doxy will decrease the chance of rupture by preventing wall weakening and maintaining function of the aorta.


Sucrose phosphate synthase expression influences poplar phenology.
The objective of this study was to manipulate the intracellular pools of sucrose, and investigate its role in regulating plant growth, phenology (leaf senescence and bud break) and fibre development. This objective was achieved by differentially expressing an Arabidopsis (Arabidopsis thaliana L. Heynh.) sucrose phosphate synthase (SPS) gene in hybrid poplar (Populus alba L.xPopulus grandidentata Michx.), a model system for tree biology with substantial industrial relevance in the context of short rotation forestry and a target bioenergy crop. Phenotypic differences were evident in the transgenic trees, as both the timing of bud flush and leaf senescence were altered compared to wild-type (WT) trees. Tree height and stem diameter were similar in WT and in the AtSPS transgenic trees, however, there were differences in the length of xylem fibres. Elevated concentrations of intracellular sucrose in both leaf and stem tissue of the transgenic trees are associated with a prolonged onset of senescence and an advancement in bud flush in the following spring. The association among sucrose content, tree phenology and elevated SPS gene expression implicates both enzyme and product in regulating poplar developmental processes.