Atomic laser-beam finder.
We report on an experimental method to align a laser beam to a cloud of atoms trapped in a magneto-optical trap (MOT). We show how balanced lock-in detection leads to a very sensitive method to align the laser beam to the atoms in the plane perpendicular to the propagation direction. This provides a very reliable and fast way of aligning laser beams to atoms trapped in a MOT.


Effects of butorphanol on morphine-induced itch and analgesia in primates.
Butorphanol is an opioid analgesic with partial agonist actions at micro- and kappa-opioid receptors (MOR and KOR). Previous studies have demonstrated that both MOR antagonists and KOR agonists are effective in alleviating intrathecal morphine-induced itch in primates. The aim of the study was to investigate the effectiveness of butorphanol as an antipruritic and to elucidate the receptor mechanisms underlying butorphanol's antipruritic effect in primates. Adult rhesus monkeys were used in the behavioral assays for measuring itch/scratching and analgesia. The dose-response curves of butorphanol were studied using selective MOR and KOR antagonists. In addition, the effect of butorphanol as an antipruritic was studied on subcutaneous and intrathecal morphine-induced itch and analgesia. KOR-selective antagonists were further used to compare the degrees of MOR and KOR activation underlying the antipruritic effect of butorphanol. Butorphanol alone produced analgesia with slight itch responses, and both effects were blocked by a MOR antagonist, clocinnamox (0.1 mg/kg). In contrast, a KOR antagonist, 5'-guanidinylnaltrindole (1 mg/kg), increased butorphanol-elicited itch. Systemic butorphanol (0.0032-0.032 mg/kg) dose-dependently attenuated systemic or intrathecal morphine-induced itch. In addition, butorphanol either potentiated or maintained morphine-induced analgesia without producing sedation. KOR-selective antagonists, 5'-guanidinylnaltrindole (1 mg/kg) and nor-binaltorphimine (3.2 mg/kg), only partially reversed the antipruritic effect of butorphanol with different durations of KOR antagonism. Butorphanol is effective in attenuating systemic or spinal morphine-induced itch without reducing morphine analgesia. This study provides functional evidence that both partial MOR and KOR agonist actions contribute to the effectiveness of butorphanol as an antipruritic in primates.


Current status of etoposide in the management of small cell lung cancer.
Etoposide is a schedule-dependent drug with excellent activity against small cell lung cancer (SCLC). Single-agent etoposide achieves overall response rates ranging from 15% to 84%, depending on the schedule of drug administration and the characteristics of the treated population. The route of etoposide administration (intravenous versus oral) has little impact on response rate, provided appropriate dose adjustments are made for oral therapy. In combination with other active agents, etoposide has proven particularly effective in the management of SCLC. Etoposide can be substituted for doxorubicin or vincristine in the cyclophosphamide, doxorubicin, and vincristine (CAV) regimen without loss of efficacy. The etoposide and cisplatin (EP) combination is thought to be synergistic and has proven to be an effective salvage regimen for CAV failures. A regimen that alternates CAV and EP has been found by some investigators to be modestly more effective against SCLC than CAV alone; however, EP alone may be as useful as an alternating regimen. Most studies to date have demonstrated that EP induction is at least as effective as any other standard induction regimen. However, EP has the potential advantage of being more easily integrated with thoracic radiation therapy (RT). This is particularly important in limited-disease patients: two recent pilot studies employing EP induction with hyperfractionated thoracic RT yielded 2-year survival rates of greater than 50%. These promising results are being evaluated further in an ongoing Phase III trial in the United States. The available data indicate that etoposide is one of the most active agents against SCLC and therefore should be included as a component of induction therapy in all patients. New schedules of etoposide administration warrant further study.


Hypoxia Potentiates the Radiation-Sensitizing Effect of Olaparib in Human Non-Small Cell Lung Cancer Xenografts by Contextual Synthetic Lethality.
Poly(ADP-ribose) polymerase (PARP) inhibitors potentiate radiation therapy in preclinical models of human non-small cell lung cancer (NSCLC) and other types of cancer. However, the mechanisms underlying radiosensitization in vivo are incompletely understood. Herein, we investigated the impact of hypoxia on radiosensitization by the PARP inhibitor olaparib in human NSCLC xenograft models. NSCLC Calu-6 and Calu-3 cells were irradiated in the presence of olaparib or vehicle under normoxic (21% O2) or hypoxic (1% O2) conditions. In vitro radiosensitivity was assessed by clonogenic survival assay and γH2AX foci assay. Established Calu-6 and Calu-3 subcutaneous xenografts were treated with olaparib (50 mg/kg, daily for 3 days), radiation (10 Gy), or both. Tumors (n=3/group) were collected 24 or 72 hours after the first treatment. Immunohistochemistry was performed to assess hypoxia (carbonic anhydrase IX [CA9]), vessels (CD31), DNA double strand breaks (DSB) (γH2AX), and apoptosis (cleaved caspase 3 [CC3]). The remaining xenografts (n=6/group) were monitored for tumor growth. In vitro, olaparib showed a greater radiation-sensitizing effect in Calu-3 and Calu-6 cells in hypoxic conditions (1% O2). In vivo, Calu-3 tumors were well-oxygenated, whereas Calu-6 tumors had extensive regions of hypoxia associated with down-regulation of the homologous recombination protein RAD51. Olaparib treatment increased unrepaired DNA DSB (P<.001) and apoptosis (P<.001) in hypoxic cells of Calu-6 tumors following radiation, whereas it had no significant effect on radiation-induced DNA damage response in nonhypoxic cells of Calu-6 tumors or in the tumor cells of well-oxygenated Calu-3 tumors. Consequently, olaparib significantly increased radiation-induced growth inhibition in Calu-6 tumors (P<.001) but not in Calu-3 tumors. Our data suggest that hypoxia potentiates the radiation-sensitizing effects of olaparib by contextual synthetic killing, and that tumor hypoxia may be a potential biomarker for selecting patients who may get the greatest benefit from the addition of olaparib to radiation therapy.


Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA.
The prevalent DNA modification in higher organisms is the methylation of cytosine to 5-methylcytosine (5mC), which is partially converted to 5-hydroxymethylcytosine (5hmC) by the Tet (ten eleven translocation) family of dioxygenases. Despite their importance in epigenetic regulation, it is unclear how these cytosine modifications are reversed. Here, we demonstrate that 5mC and 5hmC in DNA are oxidized to 5-carboxylcytosine (5caC) by Tet dioxygenases in vitro and in cultured cells. 5caC is specifically recognized and excised by thymine-DNA glycosylase (TDG). Depletion of TDG in mouse embyronic stem cells leads to accumulation of 5caC to a readily detectable level. These data suggest that oxidation of 5mC by Tet proteins followed by TDG-mediated base excision of 5caC constitutes a pathway for active DNA demethylation.


Bone remodeling-inspired dual delivery electrospun nanofibers for promoting bone regeneration.
Developing a highly bioactive bone tissue engineering scaffold that can modulate the bone remodeling process for promoting bone regeneration is a great challenge. In order to tackle this issue, inspired by the balance between bone resorption and formation in the bone remodeling process, here we developed a mesoporous silicate nanoparticle (MSN)-based electrospun polycaprolactone (PCL)/gelatin nanofibrous scaffold to achieve dual delivery of alendronate (ALN) and silicate for a synergetic effect in modulating bone remodeling, where ALN inhibited the bone-resorbing process via preventing guanosine triphosphate-related protein expression, and silicate promoted the bone-forming process via improving vascularization and bone calcification. The scaffold was successfully prepared by encapsulation of ALN into MSNs (ALN@MSNs) and co-electrospinning of an acetic acid-mediated PCL/gelatin homogeneous solution with well-dispersed ALN@MSNs. The results of ALN and Si element release profiles indicated that the ALN@MSN-loaded nanofibers achieved dual release of ALN and silicate (produced due to the hydrolysis of MSNs) simultaneously. The bone repair data from a rat critical-sized cranial defect model revealed that the developed strategy accelerated the healing time from 12 weeks to 4 weeks, almost three times faster, while the other nanofiber groups only had limited bone regeneration at 4 weeks. In addition, we used interactive double-factor analysis of variance for the data of bone volume and maturity to evaluate the synergetic effect of ALN and silicate in promoting bone regeneration, and the result clearly proved our original design and hypothesis. In summary, the presented bone remodeling-inspired electrospun nanofibers with dual delivery of ALN and silicate may be highly promising for bone repair in the clinic.


A powder made from seeds and shells of a rose-hip subspecies (Rosa canina) reduces symptoms of knee and hip osteoarthritis: a randomized, double-blind, placebo-controlled clinical trial.
The aim of this study was to determine whether a herbal remedy made from a subspecies of rose-hip (Rosa canina) might reduce symptoms of osteoarthritis and consumption of rescue medication in patients suffering from osteoarthritis. Ninety-four patients with osteoarthritis of the hip or knee were enrolled in a randomized, placebo-controlled, double-blind crossover trial. Forty-seven patients were given 5 g of the herbal remedy daily for a period of 3 months and the remaining patients were given a similar amount of placebo. The group initially treated with placebo was then changed to rose-hip and vice versa for another 3-month period. Upon inclusion and after 3 weeks and 3 months of each treatment period, pain, stiffness, disability, and global severity of the disease were scored on a Western Ontario and McMaster Universities (WOMAC) questionnaire. After 3 weeks of treatment, patients, if possible, were allowed to reduce their consumption of 'rescue medication'. Data were analysed on the basis of intention to treat. Rose-hip resulted in a significant reduction in WOMAC pain (p<0.014) as compared to placebo, when testing after 3 weeks of treatment. The consumption of 'rescue medication' significantly declined as a result of active treatment (p<0.027). WOMAC disability, stiffness, and global assessment of severity of the disease were not altered by 3 weeks but decreased significantly (p<0.018, p<0.038, and p<0.035, respectively) after 3 months of treatment. The data suggest that the present herbal remedy can alleviate symptoms of osteoarthritis and reduce the consumption of 'rescue medication'.


Dating Relationship Dynamics, Mental Health, and Dating Victimization: A Longitudinal Path Analysis.
The purpose of this study was to assess the longitudinal association between adolescent dating relationship dynamics (measures of intimacy and problem dynamics), mental health, and physical and/or sexual victimization by a dating partner. Gender-stratified analyses were conducted in a sample of 261 adolescents, ages 10-18 at baseline, interviewed in three annual waves (2013-2015) of the nationally representative Survey on Teen Relationships and Intimate Violence (STRiV). Among male daters, better mental health at baseline was negatively associated with problem dynamics at follow-up, and aspects of problem dynamics at baseline predicted worse mental health at follow-up. However, unexpectedly, aspects of relationship intimacy at baseline were also negatively associated with mental health at follow-up. Male daters' victimization did not mediate longitudinal measures of mental health or of relationship dynamics, but did predict worse mental health at follow-up. Among female daters, we found no longitudinal associations between mental health and intimacy or problem relationship dynamics, in either direction. However, victimization mediated aspects of female daters' reported relationship dynamics. Dating violence prevention efforts should reflect that adolescent females reporting controlling behaviors and feelings of passionate love may be at increased risk for victimization. Positive youth development efforts should attend to the bidirectional associations of mental health and dating relationship dynamics over time, particularly for male adolescents.


Interventions for childhood apraxia of speech.
Childhood apraxia of speech (CAS) affects a child's ability to produce sounds and syllables precisely and consistently, and to produce words and sentences with accuracy and correct speech rhythm. It is a rare condition, affecting only 0.1% of the general population. Consensus has been reached that three core features have diagnostic validity: (1) inconsistent error production on both consonants and vowels across repeated productions of syllables or words; (2) lengthened and impaired coarticulatory transitions between sounds and syllables; and (3) inappropriate prosody (ASHA 2007). A deficit in motor programming or planning is thought to underlie the condition. This means that children know what they would like to say but there is a breakdown in the ability to programme or plan the fine and rapid movements required to accurately produce speech. Children with CAS may also have impairments in one or more of the following areas: non-speech oral motor function, dysarthria, language, phonological production impairment, phonemic awareness or metalinguistic skills and literacy, or combinations of these. High-quality evidence from randomised controlled trials (RCTs) is lacking on interventions for CAS. To assess the efficacy of interventions targeting speech and language in children and adolescents with CAS as delivered by speech and language pathologists/therapists. We searched CENTRAL, MEDLINE, Embase, eight other databases and seven trial registers up to April 2017. We searched the reference lists of included reports and requested information on unpublished trials from authors of published studies and other experts as well as information groups in the areas of speech and language therapy/pathology and linguistics. RCTs and quasi-RCTs of children aged 3 to 16 years with CAS diagnosed by a speech and language pathologist/therapist, grouped by treatment types. Two review authors (FL, AM) independently assessed titles and abstracts identified from the searches and obtained full-text reports of all potentially relevant articles and assessed these for eligibility. The same two authors extracted data and conducted the 'Risk of bias' and GRADE assessments. One review author (EM) tabulated findings from excluded observational studies (Table 1). This review includes only one RCT, funded by the Australian Research Council; the University of Sydney International Development Fund; Douglas and Lola Douglas Scholarship on Child and Adolescent Health; Nadia Verrall Memorial Scholarship; and a James Kentley Memorial Fellowship. This study recruited 26 children aged 4 to 12 years, with mild to moderate CAS of unknown cause, and compared two interventions: the Nuffield Dyspraxia Programme-3 (NDP-3); and the Rapid Syllable Transitions Treatment (ReST). Children were allocated randomly to one of the two treatments. Treatments were delivered intensively in one-hour sessions, four days a week for three weeks, in a university clinic in Australia. Speech pathology students delivered the treatments in the English language. Outcomes were assessed before therapy, immediately after therapy, at one month and four months post-therapy. Our review looked at one-month post-therapy outcomes only.We judged all core outcome domains to be low risk of bias. We downgraded the quality of the evidence by one level to moderate due to imprecision, given that only one RCT was identified. Both the NDP-3 and ReST therapies demonstrated improvement at one month post-treatment. A number of cases in each cohort had recommenced usual treatment by their speech and language pathologist between one month and four months post-treatment (NDP-3: 9/13 participants; ReST: 9/13 participants). Hence, maintenance of treatment effects to four months post-treatment could not be analysed without significant potential bias, and thus this time point was not included for further analysis in this review.There is limited evidence that, when delivered intensively, both the NDP-3 and ReST may effect improvement in word accuracy in 4- to 12-year-old children with CAS, measured by the accuracy of production on treated and non-treated words, speech production consistency and the accuracy of connected speech. The study did not measure functional communication. There is limited evidence that, when delivered intensively, both the NDP-3 and ReST may effect improvement in word accuracy in 4- to 12-year-old children with CAS, measured by the accuracy of production on treated and non-treated words, speech production consistency and the accuracy of connected speech. The study did not measure functional communication. No formal analyses were conducted to compare NDP-3 and ReST by the original study authors, hence one treatment cannot be reliably advocated over the other. We are also unable to say whether either treatment is better than no treatment or treatment as usual. No evidence currently exists to support the effectiveness of other treatments for children aged 4 to 12 years with idiopathic CAS without other comorbid neurodevelopmental disorders. Further RCTs replicating this study would strengthen the evidence base. Similarly, further RCTs are needed of other interventions, in other age ranges and populations with CAS and with co-occurring disorders.


Colour Association with Music Is Mediated by Emotion: Evidence from an Experiment Using a CIE Lab Interface and Interviews.
Crossmodal associations may arise at neurological, perceptual, cognitive, or emotional levels of brain processing. Higher-level modal correspondences between musical timbre and visual colour have been previously investigated, though with limited sets of colour. We developed a novel response method that employs a tablet interface to navigate the CIE Lab colour space. The method was used in an experiment where 27 film music excerpts were presented to participants (n = 22) who continuously manipulated the colour and size of an on-screen patch to match the music. Analysis of the data replicated and extended earlier research, for example, that happy music was associated with yellow, music expressing anger with large red colour patches, and sad music with smaller patches towards dark blue. Correlation analysis suggested patterns of relationships between audio features and colour patch parameters. Using partial least squares regression, we tested models for predicting colour patch responses from audio features and ratings of perceived emotion in the music. Parsimonious models that included emotion robustly explained between 60% and 75% of the variation in each of the colour patch parameters, as measured by cross-validated R2. To illuminate the quantitative findings, we performed a content analysis of structured spoken interviews with the participants. This provided further evidence of a significant emotion mediation mechanism, whereby people tended to match colour association with the perceived emotion in the music. The mixed method approach of our study gives strong evidence that emotion can mediate crossmodal association between music and visual colour. The CIE Lab interface promises to be a useful tool in perceptual ratings of music and other sounds.


Percutaneous screw fixation for unstable scaphoid fractures.
The technique of percutaneous screw fixation, with increasing popularity, has been successfully conducted in non-displaced, stable scaphoid fractures resulting in shortened immobilization duration and prompt functional retrieval. The purpose of this study was to evaluate the surgical technique and to explore the potential benefits of using percutaneous screw fixation in unstable scaphoid fractures. Eleven of 97 patients with scaphoid fractures surgically treated between 1994 and 2002 were enrolled in this study. All were acute unstable fractures and underwent closed reduction and percutaneous screw fixation. All the records were meticulously reviewed and reported, including the complete radiographic examination before and after operation, time to fracture union, wrist motion, grip strength, and time of return to work, as well as overall patient satisfaction at the time of the most recent follow-up. Eleven fractures in an equal number of patients were followed up for a mean period of 1.6 years. All fractures acquired radiographic union in an average of 10.6 weeks. The modified Mayo Wrist score averaged 88.2. The functional result was ranked as excellent in 6 patients, and good in 5 patients. All returned to work or the pre-injury level of activity, and were satisfied with the surgical outcome. The technique of percutaneous screw fixation was successfully used to treat 11 unstable scaphoid fractures. The encouraging outcome of this treatment option and the prompt functional recovery deserve further investigation. Further randomized prospective studies to explore the specific indications and ubiquitous benefits of the technique presented herein are recommended.


Novel Development of Parafoveal Capillary Density Deviation Mapping using an Age-Group and Eccentricity Matched Normative OCT Angiography Database.
We evaluate the impact of age and signal strength index (SSI) on foveal avascular zone (FAZ) metrics and parafoveal capillary density measured using optical coherence tomography angiography (OCT-A), and propose a deviation mapping approach that accounts for age-group, SSI, eccentricity, and variation in FAZ size. Parafoveal OCT-A with full vascular layer was obtained for 261 controls and four patients with retinal abnormalities. Parafoveal capillary densities were measured within eight consecutive 200-μm wide annuli from the FAZ border. In controls, the impacts of age and SSI on FAZ metrics and parafoveal capillary density were evaluated. Deviation maps highlighting regions with density at the lower and upper tails of the age-group and eccentricity matched distribution were generated. Linear regressions showed significant correlations between age, SSI, and mean parafoveal capillary density. There was a significant difference in FAZ metrics and parafoveal capillary densities with different age groups after controlling for SSI using univariate analysis. However, the effect of age on parafoveal capillary density disappeared after controlling for SSI using multivariate linear regression analysis. Our deviation mapping approach was able to identify regions with abnormal density in four patients. Our findings suggest that the relationship between parafoveal capillary density and age is confounded by SSI. Parafoveal capillary density is SSI- and eccentricity-dependent. An age-group and eccentricity matched normative database was used as the basis for a parafoveal capillary density deviation mapping technique, providing an intuitive way to assess the status of parafoveal capillary density in individual eyes. Understanding the impact of age and SSI on parafoveal capillary density is critical for providing accurate interpretation of OCT-A. We demonstrate an age-group and eccentricity matched deviation mapping technique for an intuitive assessment of retinal regions with abnormal density.


Effects of early and intensive neuro-rehabilitative treatment on muscle synergies in acute post-stroke patients: a pilot study.
After a stroke, patients show significant modifications of neural control of movement, such as abnormal muscle co-activation, and reduced selectivity and modulation of muscle activity. Nonetheless, results reported in literature do not allow to unequivocally explain whether and, in case, how a cerebrovascular accident affects muscle synergies underlying the control of the upper limb. These discrepancies suggest that a complete understanding of the modular re-organization of muscle activity due to a stroke is still lacking. This pilot study aimed at investigating the effects of the conjunction between the natural ongoing of the pathology and the intense robot-mediated treatment on muscle synergies of the paretic upper limb of subacute post-stroke patients. Six subacute patients, homogenous with respect to the age and the time elapsed from the trauma, and ten healthy age-matched subjects were enrolled. The protocol consisted in achieving planar movement of the upper limb while handling the end-effector of a robotic platform. Patients underwent 6 weeks long treatment while clinical scores, kinematics of the end-effector and muscle activity were recorded. Then we verified whether muscle coordination underlying the motor task was significantly affected by the cerebrovascular accident and how muscle synergies were modified along the treatment. Results show that although muscle synergies in subacute stroke patients were qualitatively comparable to those of healthy subjects, those underlying the movement of the shoulder can reflect the functional deficit induced by the pathology. Moreover, the improvement of motor performance due to the treatment was achieved in conjunction with slight modifications of muscle synergies. In this regard, modifications of muscle synergies appeared to be influenced by the different recovering mechanisms across patients presumably due to the heterogeneity of lesions, sides and location of the accident. The results support the hypothesis that muscle synergies reflect the injury of the cerebrovascular accident and could document the effects of the functional recovery due to a suitable and customized treatment. Therefore, they open up new possibilities for the development of more effective neuro-rehabilitation protocols.


Impact of influenza immunization on medical expenditures among Medicare elderly, 1999-2003.
The impact of influenza immunization on expenditures for inpatient, outpatient, and professional services among elderly Medicare beneficiaries between 1999 and 2003 was examined. Data were from independent annual survey samples of 175,000 beneficiaries. Response rates ranged from 64% to 71%. Survey data included beneficiaries' demographics, education, supplemental insurance, perceived health, and influenza vaccination. Baseline measures, derived from Medicare claims for the year prior to influenza season, included service utilization, comorbidities, influenza immunization, and health status. The outcome measure was medical expenditures for acute and chronic respiratory conditions (ACRCs) for each 33-week annual influenza season. Total expenditures for ACRCs were lower among the immunized population during all four seasons. The amount and statistical significance of the savings varied with the severity of the virus and the vaccine match to the prevalent influenza strains. During the 1999-2000 influenza season, which had the most severe virus and a close vaccine match, average costs for ACRCs were $88 lower among immunized beneficiaries than among nonimmunized beneficiaries (equivalent to a 3.06% savings). During the 2002-2003 season, which had a less severe virus but the highest vaccine match rate, average costs for ACRCs were $103 lower for immunized beneficiaries than for nonvaccinated beneficiaries (equivalent to a 3.12% savings). The relative reduction in ACRC expenditures among vaccinated beneficiaries is attributable to less frequent use of inpatient services. In addition to improving the health of older Americans, meeting the Healthy People 2010 influenza immunization goal of 90% among the elderly should also result in lower Medicare expenditures.


Identification of a genetic marker for isometamidium chloride resistance in Trypanosoma congolense.
Isometamidium chloride has remained a very important prophylactic and therapeutic drug against trypanosomosis in cattle since its introduction into the market in the 1950s with, unfortunately, a concomitant development of resistance in trypanosomosis endemic areas. Amplified Fragment Length Polymorphism (AFLP) was used to compare two isogenic clones of Trypanosoma congolense. The parent clone, sensitive to isometamidium, has a CD50 (the curative dose that gives complete cure in 50% of the animals) in the mouse of 0.018 mg/kg and its derivative exposed to increasing doses of isometamidium, has a CD50 that is 94-fold higher. Sixty-four combinations of eight Eco RI and eight Mse I primers were used in comparative AFLP analysis to detect subtle genetic differences between the two clones. Thirty-five polymorphic fragments of DNA that were observed only in the resistant clone were purified and then sequenced. The nucleotide sequences were used in searching the GeneDB T. congolense database to find surrounding sequences upstream of an open reading frame and downstream to a stop codon. The sequences of the open reading frames were subsequently compared to the sequences in the genomic databases. A predicted gene coding for an 854 amino acids protein was thus identified. The protein contains a putative ATP binding site, Walker B and LSGG motifs and eight predicted trans-membrane domains. The gene in the resistant strain of T. congolense has a triplet insertion coding for an extra lysine. Using polymerase chain reaction-restriction fragment length polymorphism, the insertion was sought in the genomes of 35 T. congolense strains isolated from different geographic origins and whose response to isometamidium chloride had been determined through single dose mouse tests. The presence of the insertion, specifying an extra codon was found to always be present in the genomes of T. congolense clones that were resistant to isometamidium chloride.


BRL 49653 blocks the lipolytic actions of tumor necrosis factor-alpha: a potential new insulin-sensitizing mechanism for thiazolidinediones.
Thiazolidinediones (TZDs) such as BRL 49653 are a class of antidiabetic agents that are agonists for the peroxisome proliferator-activated nuclear receptor (PPAR-gamma2). In vivo, TZDs reduce circulating levels of free fatty acids (FFAs) and ameliorate insulin resistance in individuals with obesity and NIDDM. Adipocyte production of TNF-alpha is proposed to play a role in the development of insulin resistance, and because BRL 49653 has been shown to antagonize some of the effects of TNF-alpha, we examined the effects of TNF-alpha and BRL 49653 on adipocyte lipolysis. After a 24-h incubation of TNF-alpha (10 ng/ml) with 3T3-L1 adipocytes, glycerol release increased by approximately 7-fold, and FFA release increased by approximately 44-fold. BRL 49653 (10 pmol/l) reduced TNF-alpha-induced glycerol release by approximately 50% (P < 0.001) and FFA release by approximately 90% (P < 0.001). BRL 49653 also reduced glycerol release by approximately 50% in adipocytes pretreated for 24 h with TNF-alpha. Prolonged treatment (5 days) with either BRL 49653 or another PPAR-gamma2 agonist, 15-d delta-12,14-prostaglandin J2 (15-d deltaPGJ2), blocked TNF-alpha-induced glycerol release by approximately 100%. Catecholamine (isoproterenol)-stimulated lipolysis was unaffected by BRL 49653 and 15-d deltaPGJ2. BRL 49653 partially blocked the TNF-alpha-mediated reduction in protein levels of hormone-sensitive lipase and perilipin A, two proteins involved in adipocyte lipolysis. These data suggest a novel pathway that may contribute to the ability of the TZDs to reduce serum FFA and increase insulin sensitivity.


Predictors of career progression and obstacles and opportunities for non-EU hospital doctors to undertake postgraduate training in Ireland.
The World Health Organization's Global Code on the International Recruitment of Health Personnel urges Member States to observe fair recruitment practices and ensure equality of treatment of migrant and domestically-trained health personnel. However, international medical graduates (IMGs) have experienced difficulties in accessing postgraduate training and in progressing their careers in several destination countries. Ireland is highly dependent on IMGs, but also employs non-European Union (EU) doctors who qualified as doctors in Ireland. However, little is known regarding the career progression of these doctors. In this context, the present study assesses the determinants of career progression of non-EU doctors with particular focus on whether barriers to progression exist for those graduating outside Ireland compared to those who have graduated within. The study utilises quantitative data from an online survey of non-EU doctors registered with the Medical Council of Ireland undertaken as part of the Doctor Migration Project (2011-2013). Non-EU doctors registered with the Medical Council of Ireland were asked to complete an online survey about their recruitment, training and career experiences in Ireland. Analysis was conducted on the responses of 231 non-EU hospital doctors whose first post in Ireland was not permanent. Career progression was analysed by means of binary logistic regression analysis. While some of the IMGs had succeeded in accessing specialist training, many experienced slow or stagnant career progression when compared with Irish-trained non-EU doctors. Key predictors of career progression for non-EU doctors working in Ireland showed that doctors who qualified outside of Ireland were less likely than Irish-trained non-EU doctors to experience career progression. Length of stay as a qualified doctor in Ireland was strongly associated with career progression. Those working in anaesthesia were significantly more likely to experience career progression than those in other specialities. The present study highlights differences in terms of achieving career progression and training for Irish-trained non-EU doctors, compared to those trained elsewhere. However, the findings herein warrant further attention from a workforce planning and policy development perspective regarding Ireland's obligations under the Global Code of hiring, promoting and remunerating migrant health personnel on the basis of equality of treatment with the domestically-trained health workforce.


SELDI-TOF MS whole serum proteomic profiling with IMAC surface does not reliably detect prostate cancer.
The analysis of bodily fluids using SELDI-TOF MS has been reported to identify signatures of spectral peaks that can be used to differentiate patients with a specific disease from normal or control patients. This report is the 2nd of 2 companion articles describing a validation study of a SELDI-TOF MS approach with IMAC surface sample processing to identify prostatic adenocarcinoma. We sought to derive a decision algorithm for classification of prostate cancer from SELDI-TOF MS spectral data from a new retrospective sample cohort of 400 specimens. This new cohort was selected to minimize possible confounders identified in the previous study described in the companion paper. The resulting new classifier failed to separate patients with prostate cancer from biopsy-negative controls; nor did it separate patients with prostate cancer with Gleason scores <7 from those with Gleason scores > or =7. In this, the 2nd stage of our planned validation process, the SELDI-TOF MS-based protein expression profiling approach did not perform well enough to advance to the 3rd (prospective study) stage. We conclude that the results from our previous studies-in which differentiation between prostate cancer and noncancer was demonstrated-are not generalizable. Earlier study samples likely had biases in sample selection that upon removal, as in the present study, resulted in inability of the technique to discriminate cancer from noncancer cases.


Relationship between adhesion of Escherichia coli to uro-epithelial cells and the pathogenesis of urinary infection: problems in methodology and analysis.
Escherichia coli strains isolated from patients with urinary infections were tested for their ability to adhere to human uro-epithelial cells. In any single experiment, the numbers of bacteria adhering to individual uro-epithelial cells showed great variations; some cells had hundreds of bacteria adhering to them whereas other cells had few or none. This non-Normal distribution of bacterial attachment must be taken into account when carrying out statistical analyses of the results. The wide discrepancies reported in the literature regarding bacterial adhesion to uro-epithelial cells must, in part, be related to the type of statistical analysis used. In many cases, a Normal rather than a non-Normal distribution has been assumed. We found that even when all variables were kept constant, the experiment was still not reproducible. Therefore the technique shows a high degree of both inter- and intra-experimental error. Adhesion depended on such factors as the type of fimbriae produced by the bacteria, differing viability of uro-epithelial cells and varying pH of the medium used for a particular experiment. It is concluded that the results of in-vitro experiments demonstrating adhesion of E. coli to uro-epithelial cells are difficult to relate to bacterial adhesion in vivo but better results could be obtained if more attention were paid to standardisation of methods and their analysis.


Genomic mapping by single copy landmark detection: a predictive model with a discrete mathematical approach.
One of the goals of the Human Genome Project is to produce libraries of largely contiguous, ordered sets of molecular clones for use in sequencing and gene mapping projects. This is planned to be done for human and many model organisms. Theory and practice have shown that long-range contiguity and the degree to which the entire genome is covered by ordered clones can be affected by many biological variables. Many laboratories are currently experimenting with different experimental strategies and theoretical models to help plan strategies for accomplishing long-range molecular mapping of genomes. Here we describe a new mathematical model and formulas for helping to plan genome mapping projects, using various single-copy landmark (SCL) detection, or "anchoring", strategies. We derive formulas that allow us to examine the effects of interactions among the following variables: average insert size of the cloning vector, average size of SCL, the number of SCL, and the redundancy in coverage of the clone library. We also examine and compare three different ways in which anchoring can be implemented: (1) anchors are selected independently of the library to be ordered (random anchoring); (2) anchors are made from end probes from both ends of clones in the library to be ordered (nonrandom anchoring); and (3) anchors are made from one end or the other, randomly, from clones in the library to be ordered (nonrandom anchoring). Our results show that, for biologically realistic conditions, nonrandom anchoring is always more effective than random anchoring for contig building, and there is little to be gained from making SCL from both ends of clones vs. only one end of clones.(ABSTRACT TRUNCATED AT 250 WORDS)


Opinions on the content and effects of the Caring for Australasians with Renal Impairment (CARI) Guidelines: a survey of renal nurses and comparison with the opinions of nephrologists in Australasia.
Renal nurses in Australia and New Zealand are critical to the care of patients with chronic kidney disease (CKD), especially those on dialysis. We aimed to obtain the opinions of renal nurses in Australia and New Zealand on the Caring for Australasians with Renal Impairment (CARI) Guidelines. A self-administered survey was distributed to all members of the professional organisation for renal nurses (Renal Society of Australasia) in 2006. The results were compared with those from a similar survey in 2002 and an identical 2006 survey of Australian and New Zealand nephrologists. Of the 173 respondents, more than 95% considered the Guidelines to be a good synthesis of the available evidence, 80% indicated that the Guidelines had significantly influenced their practice and 86% considered that the Guidelines had improved patient outcomes. Older respondents were less likely to perceive that the Guidelines had improved patient outcomes, and renal nurse educators were more likely to consider that the Guidelines were based on the best available evidence than other respondents. Respondents were generally more positive about the Guidelines in 2006 than in 2002. Although nephrologists were generally positive about the CARI Guidelines, renal nurses were more positive, especially regarding the effect of the Guidelines on practice and the improvement in health outcomes. Australian and New Zealand renal nurses valued the CARI Guidelines highly, used them in practice and considered that they led to improved patient outcomes. Positive responses towards the Guidelines increased between 2002 and 2006.


Effects of transdermal tulobuterol in pediatric asthma patients on long-term leukotriene receptor antagonist therapy: results of a randomized, open-label, multicenter clinical trial in Japanese children aged 4-12 years.
Few studies have examined the efficacy or safety of a transdermal β(2) agonist as add-on medication to long-term leukotriene receptor antagonist (LTRA) therapy in pediatric asthma patients. In this randomized, open-label, multicenter clinical trial, children aged 4-12 years on long-term LTRA therapy were treated with tulobuterol patches (1-2mg daily) or oral sustained-release theophylline (usual dose, 4-5mg/kg daily) for 4 weeks. LTRAs were continued throughout the trial. Outcomes included volume of peak expiratory flow (% PEF), fractional exhaled nitric oxide (FeNO), clinical symptoms and adverse events. Thirty-three and 31 patients were treated with tulobuterol patches and theophylline, respectively. % PEF measured in the morning and before bedtime was significantly higher at all times in the treatment period compared with baseline in the tulobuterol patch group (p < 0.001), and was significantly higher in the tulobuterol patch group compared with the theophylline group. FeNO was similar and unchanged from baseline in both groups. There were no drug-related adverse events in either group. These results suggest that short-term use of a transdermal β(2) agonist is an effective therapy for pediatric asthma without inducing airway inflammation in children on long-term LTRA therapy.


Ancient origin of the modern deep-sea fauna.
The origin and possible antiquity of the spectacularly diverse modern deep-sea fauna has been debated since the beginning of deep-sea research in the mid-nineteenth century. Recent hypotheses, based on biogeographic patterns and molecular clock estimates, support a latest Mesozoic or early Cenozoic date for the origin of key groups of the present deep-sea fauna (echinoids, octopods). This relatively young age is consistent with hypotheses that argue for extensive extinction during Jurassic and Cretaceous Oceanic Anoxic Events (OAEs) and the mid-Cenozoic cooling of deep-water masses, implying repeated re-colonization by immigration of taxa from shallow-water habitats. Here we report on a well-preserved echinoderm assemblage from deep-sea (1000-1500 m paleodepth) sediments of the NE-Atlantic of Early Cretaceous age (114 Ma). The assemblage is strikingly similar to that of extant bathyal echinoderm communities in composition, including families and genera found exclusively in modern deep-sea habitats. A number of taxa found in the assemblage have no fossil record at shelf depths postdating the assemblage, which precludes the possibility of deep-sea recolonization from shallow habitats following episodic extinction at least for those groups. Our discovery provides the first key fossil evidence that a significant part of the modern deep-sea fauna is considerably older than previously assumed. As a consequence, most major paleoceanographic events had far less impact on the diversity of deep-sea faunas than has been implied. It also suggests that deep-sea biota are more resilient to extinction events than shallow-water forms, and that the unusual deep-sea environment, indeed, provides evolutionary stability which is very rarely punctuated on macroevolutionary time scales.


Concerted diffusion of lipids in raft-like membranes.
Currently, there is no comprehensive model for the dynamics of cellular membranes. The understanding of even the basic dynamic processes, such as lateral diffusion of lipids, is still quite limited. Recent studies of one-component membrane systems have shown that instead of single-particle motions, the lateral diffusion is driven by a more complex, concerted mechanism for lipid diffusion (E. Falck et al., J. Am. Chem. Soc., 2008, 130, 44-45), where a lipid and its neighbors move in unison in terms of loosely defined clusters. In this work, we extend the previous study by considering the concerted lipid diffusion phenomena in many-component raft-like membranes. This nature of diffusion phenomena emerge in all the cases we have considered, including both atom-scale simulations of lateral diffusion within rafts and coarse-grained MARTINI simulations of diffusion in membranes characterized by coexistence of raft and non-raft domains. The data allows us to identify characteristic time scales for the concerted lipid motions, which turn out to range from hundreds of nanoseconds to several microseconds. Further, we characterize typical length scales associated with the correlated lipid diffusion patterns and find them to be about 10 nm, or even larger if weak correlations are taken into account. Finally, the concerted nature of lipid motions is also found in dissipative particle dynamics simulations of lipid membranes, clarifying the role of hydrodynamics (local momentum conservation) in membrane diffusion phenomena.


Estrogenic properties of genistein acting on FSHR and LHR in rats with PCOS.
The purpose of the study was to study the activity of the phytoestrogen genistein (GEN) act- ing on FSHR and LHR in rat ovaries with polycystic ovary syndrome (PCOS). Sixty rats were di- vided into six groups. Rats in the dose group received genistein at a concentration of either 5 (low genistein dose group, L-gen), 10 (middle genistein dose group, M-Gen) or 20 (high genistein dose group, H-Gen) mg per kg of body weight per day. Estrogen group (EG, received 0.5 mg/kg Dieth- ylstilbestrol). Concentration of sex hormones in serum was quantified by enzyme-linked immuno- sorbent assay (ELISA). Expressions of follicle-stimulating hormone receptor (FSHR) and lutein- izing hormone receptor (LHR) protein were determined by immunohistochemistry. Treatment with genistein resulted in a strong stimulation of the concentration of sex hormone in serum. The concentration of progesterone and FSH was significantly higher in H-Gen when compared to the PCOS model control group (MG) (P ⟨ 0.01). In contrast, the concentration of testosterone, LH and the ratio of LH/FSH decreased in GEN treatment groups compared to MG, the effect was statistically significant, tested by the ANOVA test (p⟨0.01). For hormone receptor activity, treat- ment with genistein resulted in an improvement of ovarian function with LHR protein expression being enhanced and FSHR protein expression being suppressed. Our results demonstrate that Genistein played a significant role in regulating FSH and LH receptor expression to improve perimenopausal ovarian and uterine function.


Epidemiology of the incidence of oro-facial noma: a study of cases in Dakar, Senegal, 1981-1993.
Oro-facial noma is an oral gangrene occurring in early childhood in extremely poor areas. As many as 70-90% of those with noma die, and to date, there is no satisfactory treatment to fight this disease. Within the context of the World Health Organization international program against noma, a 13-year retrospective study based on clinical records was carried out in Dakar, Senegal in an attempt to understand the epidemiology of noma. Between 1981 and 1993, 199 cases of noma were identified, among them; 36.7% were acute cases and 63.3% showed sequelae. Chronic sequelae of noma were seen in patients 2-41 years of age, but the acute phase of noma was found only in young children (77.7% in those 1-4 years of age, maximum age = 9 years, mean age +/- SD age = 3.4 +/- 1.9 years). A total of 73.1% of the cases with acute disease were reported in the Dakar, Diourbel and Kaolack regions during the dry season (57.0% of the cases). The lesions of progressive noma were localized mainly on the upper lip (42.4%) and the cheek (31.1%). A total of 96.9% of the patients with acute diseases were had poor general health with serious associated diseases; only 20.0% had a good vital prognosis. The development of epidemiologic surveillance programs for noma should be a public health priority in Senegal.


Glaucoma in primates: cytochrome oxidase reactivity in parvo- and magnocellular pathways.
To evaluate the differential effects of ganglion cell depletion from experimental glaucoma on the relative metabolic activities of neurons in the parvo (P)- and magno (M)-cellular visual pathways of the macaque visual system. Monocular experimental glaucoma was induced in monkeys (Macaca mulatta and M. fascicularis) by applying a laser to the trabecular meshwork to increase intraocular pressure (IOP). After other behavioral and electrophysiological studies, the lateral geniculate nuclei (LGNs) and the primary visual cortices were analyzed for functional afference from surviving ganglion cells, indicated by cytochrome oxidase (CO) histochemistry. CO reactivity (COR) indicated a general reduction in neural metabolism with increasing severity of glaucoma. COR in the LGNs was reduced to the same degree in both the P- and M-cellular layers. In layer 4Cbeta of the V1 cortex, the reactivity was always reduced more than in the layer 4Calpha division. Experimental glaucoma in monkeys reduces visual afference to the central nervous system, thereby reducing the metabolic drive as indicated by COR. The detrimental effect of glaucoma did not appear to be any greater for the M-cell, rather than the P-cell pathway in the LGN or in the visual cortex. Both are affected by the duration and severity of the experimental glaucoma. Overall, the alterations in metabolism of neurons in the parallel visual pathways supplied by the Palpha and Pbeta ganglion cells do not suggest that tests based on the functional properties of one or the other would provide optimal assessment of glaucoma.


Health outcomes of HIV-exposed uninfected African infants.
To evaluate severe (grade 3/4) morbidity and mortality in HIV-exposed, uninfected infants. : Secondary data analysis of The Breastfeeding, Antiretrovirals, and Nutrition (BAN) clinical trial. BAN randomized 2369 mother-infant pairs to maternal, infant, or no extended antiretroviral prophylaxis during breastfeeding. Morbidity outcomes examined were pneumonia/serious febrile illness, diarrhea/growth faltering, and malaria. Infant death was defined as neonatal (≤30 days of life), and postneonatal (31 days to 48 weeks of life). Cox proportional hazards models were used to evaluate the effect of covariates on infant morbidity and mortality. The rate of pneumonia/serious febrile illness was highest in the first 12 weeks (0.83/100 person-weeks) before rapidly decreasing; rates of all morbidity outcomes increased after 24 weeks. Rates of pneumonia/serious febrile illness and diarrhea/growth faltering were higher during the rainy season. Prophylactic infant cotrimoxazole significantly decreased the rates of all morbidity outcomes. White blood cell (WBC) count less than 9000/μl at birth was associated with increased diarrhea/growth faltering [adjusted hazard ratio (aHR) 1.73, P = 0.04] and malaria (aHR 2.18, P = 0.02). Low birth weight (2000-2499 g) was associated with neonatal death (aHR 12.3, P < 0.001). Factors associated with postneonatal death included rainy season (aHR 4.24, P = 0.002), infant cotrimoxazole (aHR 0.48, P = 0.03), and low infant WBC count at birth (aHR 2.53, P = 0.02). Infant morbidity rates increased after 24 weeks, when BAN infants weaned. Introduction of prophylactic cotrimoxazole was associated with reduced rates of morbidity and mortality in HIV-exposed uninfected infants. Unexpectedly, a low WBC count at birth was significantly associated with later infant morbidity and mortality in this cohort.


Genome-Wide Association Study of Grain Architecture in Wild Wheat Aegilops tauschii.
Aegilops tauschii, the D-genome progenitor of Triticum aestivum, encompasses huge diversity for various traits of potential economic importance such as yield, biotic and abiotic stress tolerance, quality and nutrition. In the present study, variation for grain size in Ae. tauschii germplasm was studied and its genetic basis dissected using genome-wide association study (GWAS). Grain length, width, and weight evaluated in 177 Ae. tauschii accessions over 3 years showed near normal distribution with 1.74-, 1.75-, and 2.82-fold variation, respectively. These lines were genetically characterized using genotyping-by-sequencing (GBS) protocol that produced 11,489 single nucleotide polymorphic (SNP) markers. Genetic diversity analysis revealed the presence of two distinct subgroups (designated as lineage 1 and 2) in Ae. tauschii. Based on GBS markers, the genetic similarity was calculated between the accessions and GWAS was conducted using 114 non-redundant accessions and 5,249 SNP markers. A total of 17 SNPs associated with grain size traits distributed over all the seven chromosomes were revealed with 6D, 5D, and 2D harboring most significant marker-trait associations. Some of the chromosomal regions such as 6D_66.4-71.1 cM, 1D_143.5-156.7 cM, and 2D_89.9-92.5 cM had associations with multiple traits. Candidate genes associated with cell division and differentiation were identified for some of the associated SNP markers. Further efforts to validate these loci will help to understand their role in determining grain size and allelic diversity in current germplasm and its effect on grain size upon transfer to bread wheat background.


Validation of the Chinese (Mandarin) Version of the Oxford Knee Score in Patients with Knee Osteoarthritis.
With the increasing number of patients with knee osteoarthritis undergoing TKAs in China, there is a clear need for a valid, short, joint-specific patient-reported outcome measure such as the Oxford Knee Score (OKS). To test the translated and cross-culturally adapted Chinese (Mandarin) version of the Oxford Knee Score (OKS-CV) and its (1) reliability, (2) construct validity, (3) dimensionality, and (4) responsiveness. Three native Chinese bilingual translators (a professional English translator, an experienced orthopaedic surgeon, an advanced-practice nursing specialist) translated the English-language OKS into Mandarin Chinese. A consensus panel created a synthesis of those efforts, which then was back-translated by two bilingual nonmedical, professional English-language translators. The OKS-CV was developed according to the guidelines of copyright holders. Between March 2013 and March 2015, 253 patients underwent TKAs. Among them, 114 Mandarin-speaking patients with knee osteoarthritis underwent primary unilateral TKA (age, 67 ± 7 years; range, 55-84 years; female, 80%; preoperatively 54% had moderate to severe knee osteoarthritis), completed the preoperative questionnaires, and were followed up, with a mean postoperative followup of 2.7 years (SD, 0.5 years). Eligibility criteria were (1) patients with knee osteoarthritis who were scheduled to have a primary unilateral TKA, (2) patients who were fluent in Mandarin, and (3) consent to participate. The exclusion criteria were: (1) lack of understanding of Mandarin, and (2) inability to comprehend the questionnaires owing to cognitive impairment. To evaluate test-retest reliability, another group of 35 Mandarin-speaking outpatients with knee osteoarthritis (age, 61 ± 10 years; range, 44-84 years; female, 77%) was recruited to complete the OKS-CV twice at a 1-week interval. Reliability was tested using Cronbach's alpha and intraclass correlation coefficient (ICC). Construct validity was evaluated using Spearman's rank correlation coefficient to quantify the correlations between the OKS-CV and the WOMAC, Short Form-8 Health Survey (SF-8TM), and EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D). Exploratory factor analysis was performed to clarify dimensionality. The eigenvalue indicates the importance of each factor obtained from factor analysis. Responsiveness was determined by standardized response mean (SRM) and effect size (ES) from preoperative and postoperative scores of the OKS-CV. Floor and ceiling effects also were analyzed. The internal consistency (Cronbach's alpha = 0.89) and test-retest reliability (ICC = 0.93; 95% CI, 0.87-0.97) proved good. Convergent construct validity was supported by moderate to strong correlations between the OKS-CV and the WOMAC (r = -0.80, p < 0.001), the SF-8TM physical component summary (r = 0.65, p < 0.001), and the EQ-5D usual activities (r = -0.41, p < 0.001) and mobility (r = -0.35, p < 0.001). There also were correlations between the OKS-CV and the SF-8TM mental component summary (r = 0.58, p < 0.001) and the EQ-5D anxiety/depression (r = -0.35, p < 0.001). The factor analysis yielded three factors with eigenvalues greater than 1. Responsiveness was excellent (SRM = 1.52; ES = 1.52). No floor or ceiling effect was observed. The OKS-CV showed good acceptability and psychometric properties for the intended population. Future studies are needed to evaluate the mental state of patients with knee osteoarthritis. The OKS-CV appears to be a reliable, valid, and responsive instrument for Chinese patients with knee osteoarthritis. Based on these results we believe the OKS-CV can be used as a valuable tool for the assessment of patient-reported outcomes in Chinese patients with knee osteoarthritis before and after TKA.


Environmental microbiology through the lens of high-throughput DNA sequencing: synopsis of current platforms and bioinformatics approaches.
The incursion of High-Throughput Sequencing (HTS) in environmental microbiology brings unique opportunities and challenges. HTS now allows a high-resolution exploration of the vast taxonomic and metabolic diversity present in the microbial world, which can provide an exceptional insight on global ecosystem functioning, ecological processes and evolution. This exploration has also economic potential, as we will have access to the evolutionary innovation present in microbial metabolisms, which could be used for biotechnological development. HTS is also challenging the research community, and the current bottleneck is present in the data analysis side. At the moment, researchers are in a sequence data deluge, with sequencing throughput advancing faster than the computer power needed for data analysis. However, new tools and approaches are being developed constantly and the whole process could be depicted as a fast co-evolution between sequencing technology, informatics and microbiologists. In this work, we examine the most popular and recently commercialized HTS platforms as well as bioinformatics methods for data handling and analysis used in microbial metagenomics. This non-exhaustive review is intended to serve as a broad state-of-the-art guide to researchers expanding into this rapidly evolving field.


Safer sexual behaviors after 12 months of antiretroviral treatment in Mombasa, Kenya: a prospective cohort.
Roll-out of antiretroviral treatment (ART) raises concerns about the potential for unprotected sex if sexual activity increases with well-being, resulting in continued HIV spread. Beliefs about reduced risk for HIV transmission with ART may also influence behavior. From September 2003 to November 2004, 234 adults enrolled in a trial assessing the efficacy of modified directly observed therapy in improving adherence to ART. Unsafe sexual behavior (unprotected sex with an HIV-negative or unknown status partner) before starting ART and 12 months thereafter was compared. Participants were a mean 37.2 years (standard deviation [SD] = 7.9 years) and 64% (149/234) were female. Nearly half (107/225) were sexually active in the 12 months prior to ART, the majority (96/107) reporting one sexual partner. Unsafe sex was reported by half of those sexually active in the 12 months before ART (54/107), while after 12 months ART, this reduced to 28% (30/107). Unsafe sex was associated with nondisclosure of HIV status to partner; recent HIV diagnosis; not being married or cohabiting; stigma; depression and body mass index <18.5 kg/m(2). ART beliefs, adherence, and viral suppression were not associated with unsafe sex. After adjusting for gender and stigma, unsafe sex was 0.59 times less likely after 12 months ART than before initiation (95% confidence interval [CI] = 0.37-0.94; p = 0.026). In conclusion, although risky sexual behaviors had decreased, a considerable portion do not practice safe sex. Beliefs about ART's effect on transmission, viral load, and adherence appear not to influence sexual behavior but require long-term surveillance. Positive prevention interventions for those receiving ART must reinforce safer sex practices and partner disclosure.


Study Habits, Skills, and Attitudes: The Third Pillar Supporting Collegiate Academic Performance.
Study habit, skill, and attitude inventories and constructs were found to rival standardized tests and previous grades as predictors of academic performance, yielding substantial incremental validity in predicting academic performance. This meta-analysis (N = 72,431, k = 344) examines the construct validity and predictive validity of 10 study skill constructs for college students. We found that study skill inventories and constructs are largely independent of both high school grades and scores on standardized admissions tests but moderately related to various personality constructs; these results are inconsistent with previous theories. Study motivation and study skills exhibit the strongest relationships with both grade point average and grades in individual classes. Academic specific anxiety was found to be an important negative predictor of performance. In addition, significant variation in the validity of specific inventories is shown. Scores on traditional study habit and attitude inventories are the most predictive of performance, whereas scores on inventories based on the popular depth-of-processing perspective are shown to be least predictive of the examined criteria. Overall, study habit and skill measures improve prediction of academic performance more than any other noncognitive individual difference variable examined to date and should be regarded as the third pillar of academic success.


Spine imaging after lumbar disc replacement: pitfalls and current recommendations.
Most lumbar artificial discs are still composed of stainless steel alloys, which prevents adequate postoperative diagnostic imaging of the operated region when using magnetic resonance imaging (MRI). Thus patients with postoperative radicular symptoms or claudication after stainless steel implants often require alternative diagnostic procedures. Possible complications of lumbar total disc replacement (TDR) are reviewed from the available literature and imaging recommendations given with regard to implant type. Two illustrative cases are presented in figures. Access-related complications, infections, implant wear, loosening or fracture, polyethylene inlay dislodgement, facet joint hypertrophy, central stenosis, and ankylosis of the operated segment can be visualised both in titanium and stainless steel implants, but require different imaging modalities due to magnetic artifacts in MRI. Alternative radiographic procedures should be considered when evaluating patients following TDR. Postoperative complications following lumbar TDR including spinal stenosis causing radiculopathy and implant loosening can be visualised by myelography and radionucleotide techniques as an adjunct to plain film radiographs. Even in the presence of massive stainless steel TDR implants lumbar radicular stenosis and implant loosening can be visualised if myelography and radionuclide techniques are applied.


Examining the Relationship between Park Neighborhoods, Features, Cleanliness, and Condition with Observed Weekday Park Usage and Physical Activity: A Case Study.
Little research has comprehensively explored how park features, quality indicators, and neighborhood environments are associated with observed park usage and physical activity (PA). This case study examined whether weekday park usage and PA differ by neighborhood type, across numerous categories of park features, and according to park feature condition and cleanliness. Direct observation was used to capture the number of users and PA levels within 143 park features in 6 parks (3 urban, 3 suburban) over the course of six weeks. Audits of park environments assessed the type, condition, and cleanliness of all features and amenities. Urban parks experienced greater usage, but a higher proportion of sedentary users than suburban parks. Usage and PA levels differed across types of park features, with splash pads, pools, paths, and play structures having the greatest proportion of active users. Usage did not differ by park feature condition and cleanliness, but greater condition and cleanliness were generally associated with higher PA levels. Factors such as neighborhood context, types of park features, and condition and cleanliness can impact park usage and PA levels and should be targets for researchers and planners aiming to foster more user-friendly and active neighborhood park environments.


Meningeal CGRP-Prolactin Interaction Evokes Female-Specific Migraine Behavior.
Migraine is three times more common in women. CGRP plays a critical role in migraine pathology and causes female-specific behavioral responses upon meningeal application. These effects are likely mediated through interactions of CGRP with signaling systems specific to females. Prolactin (PRL) levels have been correlated with migraine attacks. Here, we explore a potential interaction between CGRP and PRL in the meninges. Prolactin, CGRP, and receptor antagonists CGRP8-37 or Δ1-9-G129R-hPRL were administered onto the dura of rodents followed by behavioral testing. Immunohistochemistry was used to examine PRL, CGRP and Prolactin receptor (Prlr) expression within the dura. Electrophysiology on cultured and back-labeled trigeminal ganglia (TG) neurons was used to assess PRL-induced excitability. Finally, the effects of PRL on evoked CGRP release from ex vivo dura were measured. We found that dural PRL produced sustained and long-lasting migraine-like behavior in cycling and ovariectomized female, but not male rodents. Prlr was expressed on dural afferent nerves in females with little-to-no presence in males. Consistent with this, PRL increased excitability only in female TG neurons innervating the dura and selectively sensitized CGRP release from female ex vivo dura. We demonstrate crosstalk between PRL and CGRP systems as CGRP8-37 decreases migraine-like responses to dural PRL. Reciprocally, Δ1-9-G129R-hPRL attenuates dural CGRP-induced migraine behaviors. Similarly, Prlr deletion from sensory neurons significantly reduced migraine-like responses to dural CGRP. This CGRP-PRL interaction in the meninges is a mechanism by which these peptides could produce female-selective responses and increase the prevalence of migraine in women. ANN NEUROL 2021;89:1129-1144.


Aneurysmal benign fibrous histiocytoma of the anal canal: a rare differential diagnosis.
To our knowledge, we report the first case of an aneurysmal benign fibrous histiocytoma occurring in the anal canal. Clinical, histological, radiological and surgical data pertaining to this patient were analysed. Additionally, a literature review on aneurysmal benign fibrous histiocytoma was conducted. We describe a 48-year-old Caucasian male presenting with a 2-week history of a painful anus, fresh rectal bleeding and tenesmus. Digital rectal examination identified a tender firm mass in the anal verge. Magnetic resonance imaging revealed high signal in the anal canal. Flexible sigmoidoscopy revealed an ulcerated 3-cm indurated lesion at the four o'clock position. Biopsies taken of the mass confirmed the diagnosis of an aneurysmal benign fibrous histiocytoma (BFH). Following a discussion in the colorectal multi-disciplinary team, the patient was counselled for an excision of the lesion. Diathermy dissection was performed to completely excise the tumour with a margin involving the fibres of the anal sphincter. The patient made a full recovery and had no residual symptoms. Histology of the excised specimen confirmed clear margins of the BFH. This paper aims to highlight a rare differential diagnosis for an anal mass. An aneurysmal BFH most often presents as a painless mass within the dermis and subcutaneous tissue. As such, this case presents a diagnostic challenge to both colorectal surgeon and histopathologist due to its low incidence and unusual location. We further present the clinical and radiographic evidence to confirm the diagnosis. Additionally, we discuss the literature pertaining to this condition and its optimal management.


Thromboelastogram-guided enoxaparin dosing does not confer protection from deep venous thrombosis: a randomized controlled pilot trial.
The incidence of deep venous thrombosis (DVT) remains high in general surgery and trauma patients despite widespread prophylaxis with enoxaparin. A recent study demonstrated decreased incidence of DVT if patients on enoxaparin had a change in R time (ΔR) of greater than 1 minute when heparinase-activated thromboelastography (TEG) was compared with normal TEG. We hypothesized that using ΔR-guided dosing would result in decreased DVT rates. A prospective, randomized controlled trial was performed at a Level 1 trauma center. Both trauma and general surgery patients were included. Upon enrollment, demographic data including age, sex, body mass index, and Acute Physiology and Chronic Health Evaluation II score were obtained. Enrolled patients were randomized to standard (30 mg twice a day) or TEG-guided dosing. Dose-adjusted patients underwent daily enoxaparin titration to achieve an ΔR of 1 minute to 2 minutes. Venous thromboembolism screening was performed per institutional protocol. Antithrombin III (AT-III) and anti-Xa levels were drawn at peak enoxaparin concentrations. A total of 87 patients were enrolled. There was no difference in demographic data between the groups. No pulmonary emboli were identified. The control group had a DVT rate of 16%, while the experimental group had a rate of 14% (p = nonsignificant). The experimental group's median enoxaparin dosage, 50 mg twice a day, was significantly higher than that of the control (p < 0.01). TEG ΔR was not different between the control and experimental groups. Beginning at Day 3, anti-Xa levels were higher in the experimental group (p < 0.05). There was no difference in AT-III activity between the two groups; 67% of the patients demonstrated AT-III deficiency. TEG adjusted enoxaparin dosing led to significant increases in anti-Xa activity, which did not correlate with a decreased DVT rate. Failure to reduce the DVT rate and increase ΔR despite increased dosing and increased anti-Xa activity is consistent with the high rate of AT-III deficiency detected in this study cohort. These data suggest that the future of DVT prevention may not lie in the optimization of low molecular weight heparin therapy but rather in compounds that increase antithrombin directly or operate independently of the AT-III pathway. Therapeutic study, level III.


Comano's (Trentino) thermal water interferes with the expression and secretion of vascular endothelial growth factor-A protein isoforms by cultured human psoriatic keratinocytes: a potential mechanism of its anti-psoriatic action.
Thermal balneotherapy with Comano spa's water (CW; Trentino, Italy) is used for psoriasis and other skin disorders but the mechanism(s) of action of this hypotonic water are unknown. Since skin psoriatic manifestations are thought to be angiogenesis-dependent, we assessed CW's effects on the expression and release of VEGF-A protein isoforms by cultured human lesional keratinocytes isolated from skin biopsies performed in 9 patients. Confluent, psoriatic keratinocytes were exposed for 11 days to DMEM, whose chemicals had been dissolved in either deionised water (DW-DMEM, controls) or CW (CW-DMEM, treated cells). As detected by Western immunoblotting (WB), incubation in CW-DMEM elicited, with respect to DW-DMEM, an increase in intracellular and/or cell-bound L-VEGF-A189 and L-VEGF-A165 48 kDa protein isoforms with no concurrent change in L-VEGF-A121 and L-VEGF-A165 45 kDa proteins. Moreover, WB analysis of the secreted VEGF-A (sVEGF-A) proteins showed that the 20 and 15 kDa bands corresponding to different VEGF-A isoforms were directly and remarkably reduced in keratinocyte-conditioned CW-DMEM vs. DW-DMEM. Thus, CW interferes with VEGF-A isoform expression and secretion by the psoriatic keratinocytes. These effects would reduce all VEGF-A-mediated angiogenic, vessel permeabilising, and chemotactic effects, thereby at least in part explaining the beneficial actions of CW balneotherapy on the clinical manifestations of psoriasis.


Peers experience of delivering a problem-solving programme to enhance antipsychotic medication adherence for individuals with schizophrenia.
No research has been conducted into the experience of peer support in improving adherence with oral antipsychotic medication for consumers with schizophrenia. Altruism influences peers to participate in peer support. Engagement in peer support can be challenging and rewarding for peers, and helps improve their own confidence and well-being. Many consumers with schizophrenia are reluctant to take their prescribed antipsychotic medications; however, non-adherence can lead to relapse. The aim of this study was to evaluate peers' perspectives of their participation in a problem-solving peer support programme to enhance adherence in consumers who are reluctant to take antipsychotic medication. Peers contacted consumers by a weekly telephone call for 8 weeks, and used a problem-solving approach to inform their discussion about medication adherence. Semi-structured qualitative interviews were used to evaluate peers' perspectives of their involvement in the programme. Three main themes were abstracted from the data: motivation to participate in the study, experience of peer support programme, and rewards and challenges of the peer experience. Helping others was an important motivator for peers in agreeing to participate in the study. Telephone delivery was a convenient way to deliver the peer support programme. However, at times, it was difficult to contact consumers by telephone and this caused some frustration. Despite these difficulties, peers recognized that being involved in the programme increased their confidence and made them feel worthwhile. The findings have implications for the use of peer support as an adjunct intervention to promote medication adherence in consumers with schizophrenia.


Managing Floral Resources in Apple Orchards for Pest Control: Ideas, Experiences and Future Directions.
Functional biodiversity is of fundamental importance for pest control. Many natural enemies rely on floral resources to complete their life cycle. Farmers need to ensure the availability of suitable and sufficient floral biodiversity. This review summarizes 66 studies on the management of floral biodiversity in apple orchards, published since 1986. Approaches followed different degrees of intervention: short-term practices (mowing regime and weed maintenance, cover crops), establishment of durable ecological infrastructures (perennial flower strips, hedgerows) and re-design of the crop system (intercropping, agroforestry). Although short-term practices did not always target the nutrition of natural enemies by flowering plants, living conditions for them (alternative prey, provision of habitat) were often improved. Perennial flower strips reliably enhanced natural enemies and techniques for their introduction continuously developed. Resident natural enemies and their impact in pest control reacted positively to the introduction of a more diversified vegetation, whereas the response of very mobile organisms was often not directly linked to the measures taken. A careful selection and management of plants with particular traits exploitable by most natural enemies emerged as a key-point for success. Now the elaborated design of such measures needs to be adopted by stakeholders and policy makers to encourage farmers to implement these measures in their orchards.


Applying participatory design to a pharmacy system intervention.
Stakeholder engagement is an important component of the research process for improving the use and uptake of patient-centered health care innovations. Participatory design (PD), a method that utilizes the involvement of patients and other stakeholders, is well-suited for the design of multifaceted interventions in complex work systems, such as community pharmacies, that have diverse and dynamic end-users. The objective is to describe a blueprint for how to use PD when designing a community pharmacy intervention. This paper outlines the steps of PD and highlights the advantages and disadvantages of this method. PD is explained step-wise to underscore the considerations required of researchers unfamiliar with PD. This includes the development of a tailored PD approach, PD session preparatory work, data collection, and intervention development and evaluation. The stakeholders recruited for the community pharmacy intervention were pharmacy staff and older adult patients who received prescriptions at the pharmacy corporation in which the intervention was being implemented. The PD process was a series of six adaptive sessions: (1) problem identification, (2) solution generation, (3) convergence, (4) prototyping, (5) initial evaluation, and (6) formative evaluation. A description of the PD process to design a community pharmacy intervention is provided. The process led to the development of a patient-centered prototype. The advantages of using PD included the opportunity to clarify problems faced by stakeholders, generation of novel solutions to incorporate into the intervention, and the ability to vet and fine-tune stakeholder design ideas in an iterative fashion. The insight gained was unprecedented and invaluable to the researchers. The biggest challenge of employing PD was the time-sensitive and time-intensive nature of developing each session, collecting data, and reflecting on the results in order to design subsequent sessions. The PD process led to the development of a patient-centered prototype. PD enabled stakeholders to generate creative solutions and provide unique insight on addressing issues faced in healthcare redesign research and specifically in community pharmacies.


Synthesis and solution-phase conformation of the RG-I fragment of the plant polysaccharide pectin reveals a modification-modulated assembly mechanism.
The syntheses of pure RG-I fragments of key plant matrix biomolecule pectin using a counterintuitive late-stage convergent cis-glycosylation has allowed detailed analyses of their solution-phase conformations, metal binding affinities, pK(a) values, self-assembly equilibria, and diffusional kinetics. These reveal a striking, right-handed 3(1)-helix that provides an effective and repeating lateral display of putative liganding carboxylates. Moreover, these heteropolymeric structures allow units as short as tetrasaccharides to self-assemble through carbohydrate-carbohydrate interactions that are induced by the presence of Ca(II), a known dynamic trigger in planta. These self-assembly properties can be switched simply by the addition or removal of a single methyl group in this repeating unit through methyl (de)esterification, another known dynamic trigger in planta. Together, the combined effect of Ca(II) and methylation revealed here suggests a concerted molecular basis for these two major dynamic modifications in planta.


A rare case of symptomatic hyperparathyroidism in an elderly patient with dual pathology.
Primary hyperparathyroidism secondary to true sporadic synchronous parathyroid cancer (PTCa) and adenoma (PTa) is rare. This is a case of an 80-year-old female admitted with symptomatic hypercalcaemia, raised serum calcium (Ca) of 3.39 mmol/L and raised parathyroid hormone (PTH) of 44.3 pmol/L. Ultrasonic evaluation of the neck revealed a mass posterior to the right thyroid lobe. Imaging of the left neck was unremarkable. Subsequent sesta-MIBI and single-photon emission computed tomography-computed tomography (SPECT-CT) scanning highlighted conspicuous activity over the right lower neck consistent with the neck ultrasound scan findings. Pre-operatively, PTa was suspected. Intra-operatively, malignancy was suspected due to infiltration of the parathyroid tumour into the thyroid. The right inferior parathyroid and right thyroid gland were resected. Histology confirmed PTCa. Despite surgical treatment, she was found to have persistently high Ca and PTH levels. Further investigation with a repeat sesta-MIBI and SPECT-CT suggested a left inferior parathyroid tumour. Excision of this mass revealed a PTa. Recovery was unremarkable and serum biochemistry returned to normal ranges.


Regulation of the voltage-gated K+ channel KCNA10 by KCNA4B, a novel beta-subunit.
Voltage-gated K+ (Kv) channels are heteromultimeric complexes consisting of pore-forming alpha-subunits and accessory beta-subunits. Several beta-subunits have been identified and shown to interact with specific alpha-subunits to modify their levels of expression or some of their kinetic properties. The aim of the present study was to isolate accessory proteins for KCNA10, a novel Kv channel alpha-subunit functionally related to Kv and cyclic nucleotide-gated cation channels. Because one distinguishing feature of KCNA10 is a putative cyclic nucleotide-binding domain located at the COOH terminus, the entire COOH-terminal region was used to probe a human cardiac cDNA library using the yeast two-hybrid system. Interacting clones were then rescreened in a functional assay by coinjection with KCNA10 in Xenopus oocytes. One of these clones (KCNA4B), when injected alone in oocytes, produced no detectable current. However, when coinjected with KCNA10, it increased KCNA10 current expression by nearly threefold. In addition, the current became more sensitive to activation by cAMP. KCNA4B can be coimmunoprecipitated with the COOH terminus of KCNA10 and full-length KCNA10. It encodes a soluble protein (141 aa) with no amino acid homology to known beta-subunits but with limited structural similarity to the NAD(P)H-dependent oxidoreductase superfamily. KCNA4B is located on chromosome 13 and spans approximately16 kb, and its coding region is made up of five exons. In conclusion, KCNA4B represents the first member of a new class of accessory proteins that modify the properties of Kv channels.


Characterization of the KLP68D kinesin-like protein in Drosophila: possible roles in axonal transport.
This paper describes the molecular and biochemical properties of KLP68D, a new kinesin-like motor protein in Drosophila melanogaster. Sequence analysis of a full-length cDNA encoding KLP68D demonstrates that this protein has a domain that shares significant sequence identity with the entire 340-amin acid kinesin heavy chain motor domain. Sequences extending beyond the motor domain predict a region of alpha-helical coiled-coil followed by a globular "tail" region; there is significant sequence similarity between the alpha-helical coiled-coil region of the KLP68D protein and similar regions of the KIF3 protein of mouse and the KRP85 protein of sea urchin. This finding suggests that all three proteins may be members of the same family, and that they all perform related functions. KLP68D protein produced in Escherichia coli is, like kinesin itself, a plus-end directed microtubule motor. In situ hybridization analysis of KLP68D RNA in Drosophila embryos indicates that the KLP68D gene is expressed primarily in the central nervous system and in a subset of the peripheral nervous system during embryogenesis. Thus, KLP68D may be used for anterograde axonal transport and could conceivably move cargoes in fly neurons different than those moved by kinesin heavy chain or other plus-end directed motors.


Analysis of reproducibility and sensitivity of atraumatic measurements of regional cerebral blood flow in cerebrovascular diseases.
We tested the reproducibility of consecutive measurements of regional cerebral blood flow (rCBF) made in 13 areas of each hemisphere in patients with cerebrovascular diseases by the atraumatic 133Xe intravenous injection method. The data were analysed by a two-compartment model similar to that used in the Obrist inhalation method. Four parameters derived from the model were tested: Fg (flow of the fast-clearing compartment), FF and W (respectively fractional flow and relative tissue weight of the same compartment), ISI (initial slope index as defined by Risberg et al.). No significant variation was found in these four parameters between two consecutive rest measurements for all the areas studied and whatever the time interval between the measurements. The variances of the differences of Fg and ISI between the two measurements were found to be similar to those found in normal healthy subjects. The variances of FF and, consequently, W were greater than the values determined in healthy volunteers. An attempt to improve the quality of the results, by correcting them for the effects of PaCO2 changes between the measurements, resulted on the contrary in a general increase of the variances of the differences, showing the inadequacy of the correction coefficients used for healthy subjects at least for a proportion of the patients with cerebrovascular diseases. Sensitivity, tested by activation (hand work), shows a positive answer for FG but no significant change in ISI in any area. These findings demonstrate that in cases of cerebrovascular diseases the raw data (uncorrected for the changes in PaCO2) are the most reliable data but the meaning of the values found for FF and W must be regarded with caution since they may be affected by the "slippage" phenomenon. It is suggested that the ISI should only be used when there is evidence of a failure of the compartmental model, but only as a rough estimation of the flow level because of its lack of sensitivity.


Optimization of 5-flurouracil solid-lipid nanoparticles: a preliminary study to treat colon cancer.
Solid lipid nanoparticle (SLNs) formulae were utilized for the release of 5-flurouracil (5-FU) inside the colonic medium for local treatment of colon cancer. SLNs were prepared by double emulsion-solvent evaporation technique (w/o/w) using triglyceride esters, Dynasan™ 114 or Dynasan™ 118 along with soyalecithin as the lipid parts. Different formulation parameters; including type of Dynasan, soyalicithin:Dynasan ratio, drug:total lipid ratio, and polyvinyl alcohol (PVA) concentration were studied with respect to particle size and drug entrapment efficiency. Results showed that formula 8 (F8) with composition of 20% 5-FU, 27% Dynasan™ 114, and 53% soyalithicin andformula 14 (20% 5-FU, 27% Dynasan™ 118, and 53% soyalithicin), which were stabilized by 0.5% PVA, as well as F10 with similar composition as F8 but stabilized by 2% PVA were considered the optimum formulae as they combined small particle size and relatively high encapsulation efficiencies. F8 had a particle size of 402.5 nm ± 34.5 with a polydispersity value of 0.005 and an encapsulation efficiency of 51%, F10 had a 617.3 ± 54.3 nm particle size with 0.005 polydispersity value and 49.1% encapsulation efficiency, whereas formula F14 showed a particle size of 343 nm ± 29 with 0.005 polydispersity, and an encapsulation efficiency of 59.09%. DSC and FTIR results suggested the existence of the lipids in the solid crystalline state. Incomplete biphasic prolonged release profile of the drug from both formulae was observed in phosphate buffer pH 6.8 as well as simulated colonic medium containing rat caecal contents. A burst release with magnitudes of 26% and 28.8% cumulative drug released were noticed in the first hour samples incubated in phosphate buffer pH 6.8 for both F8 and F14, respectively, followed by a slow release profile reaching 50% and 52% after 48 hours.


Facilitation of muscle evoked responses after repetitive cortical stimulation in man.
The technique of repetitive transcranial magnetic stimulation (rTMS) allows cortical motor areas to be activated by trains of magnetic stimuli at different frequencies and intensities. In this paper, we studied long-term neurophysiological effects of rTMS delivered to the motor cortex at 5 Hz with an intensity of 120% of motor threshold. Each stimulus of the train produced muscle-evoked potentials (MEPs) in hand and forearm muscles, which gradually increased in size from the first to the last shock. After the end of the train, the response to a single-test stimulus remained enhanced for 600-900 ms. In contrast, the train had no effect on the size of the MEPs evoked by transcranial electrical stimulation, while it suppressed H-reflexes in forearm muscles for 900 ms. We conclude that rTMS of these parameters increases the excitability of the motor cortex and that this effect outlasts the train for almost 1 s. At the spinal level, rTMS may increase presynaptic inhibition of Ia afferent fibers responsible for the H-reflex.


Field camera measurements of gradient and shim impulse responses using frequency sweeps.
Applications of dynamic shimming require high field fidelity, and characterizing the shim field dynamics is therefore necessary. Modeling the system as linear and time-invariant, the purpose of this work was to measure the impulse response function with optimal sensitivity. Frequency-swept pulses as inputs are analyzed theoretically, showing that the sweep speed is a key factor for the measurement sensitivity. By adjusting the sweep speed it is possible to achieve any prescribed noise profile in the measured system response. Impulse response functions were obtained for the third-order shim system of a 7 Tesla whole-body MR scanner. Measurements of the shim fields were done with a dynamic field camera, yielding also cross-term responses. The measured shim impulse response functions revealed system characteristics such as response bandwidth, eddy currents and specific resonances, possibly of mechanical origin. Field predictions based on the shim characterization were shown to agree well with directly measured fields, also in the cross-terms. Frequency sweeps provide a flexible tool for shim or gradient system characterization. This may prove useful for applications involving dynamic shimming by yielding accurate estimates of the shim fields and a basis for setting shim pre-emphasis.


Internal and near-surface electromagnetic fields for a dielectric spheroid illuminated by a zero-order Bessel beam.
Within the framework of generalized Lorenz-Mie theory, scattering from a homogeneous spheroidal particle illuminated by an on-axis zero-order Bessel beam is formulated analytically, with special attention paid to the investigation of internal and near-surface fields. Numerical results concerning the spatial distributions of internal and near-surface fields are presented for various parameter values, such as the half-cone angle of the incident zero-order Bessel beam, the major axis, the minor axis, and the refractive index of the spheroid. The study of internal and near-surface field distributions will contribute to the understanding of Bessel beam scattering by nonspherical particles with sizes close to the incident wavelength.


Work history and radioprotection practices in relation to cancer incidence and mortality in US radiologic technologists performing nuclear medicine procedures.
Technologists working in nuclear medicine (NM) are exposed to higher radiation doses than most other occupationally exposed populations. The aim of this study was to estimate the risk of cancer in NM technologists in relation to work history, procedures performed and radioprotection practices. From the US Radiologic Technologists cohort study, 72 755 radiologic technologists who completed a 2003-2005 questionnaire were followed for cancer mortality through 31 December 2012 and for cancer incidence through completion of a questionnaire in 2012-2013. Multivariable-adjusted models were used to estimate HRs for total cancer incidence and mortality by history of ever performing NM procedures and frequency of performing specific diagnostic or therapeutic NM procedures and associated radiation protection measures by decade. During follow-up (mean=7.5 years), 960 incident cancers and 425 cancer deaths were reported among the 22 360 technologists who worked with NM procedures. We observed no increased risk of cancer incidence (HR 0.96, 95% CI 0.89 to 1.04) or death (HR 1.05, 95% CI 0.93 to 1.19) among workers who ever performed NM procedures. HRs for cancer incidence but not mortality were higher for technologists who began performing therapeutic procedures in 1960 and later compared with the 1950s. Frequency of performing diagnostic or therapeutic NM procedures and use of radioprotection measures were not consistently associated with cancer risk. No clear associations were observed for specific cancers, but results were based on small numbers. Cancer incidence and mortality were not associated with NM work history practices, including greater frequency of procedures performed.


Mathematical model of the neonatal mouse ventricular action potential.
Therapies for heart disease are based largely on our understanding of the adult myocardium. The dramatic differences in action potential (AP) shape between neonatal and adult cardiac myocytes, however, indicate that a different set of molecular interactions in neonatal myocytes necessitates different treatment for newborns. Computational modeling is useful for synthesizing data to determine how interactions between components lead to systems-level behavior, but this technique has not been used extensively to study neonatal heart cell function. We created a mathematical model of the neonatal (day 1) mouse myocyte by modifying, on the basis of experimental data, the densities and/or formulations of ion transport mechanisms in an adult cell model. The new model reproduces the characteristic AP shape of neonatal cells, with a brief plateau phase and longer duration than the adult (action potential duration at 80% repolarization = 60.1 vs. 12.6 ms). The simulation results are consistent with experimental data, including 1) decreased density and altered inactivation of transient outward K+ currents, 2) increased delayed rectifier K+ currents, 3) Ca2+ entry through T-type as well as L-type Ca2+ channels, 4) increased Ca2+ influx through Na+/Ca2+ exchange, and 5) Ca2+ transients resulting from transmembrane Ca2+ entry rather than release from the sarcoplasmic reticulum (SR). Simulations performed with the model generated novel predictions, including increased SR Ca2+ leak and elevated intracellular Na+ concentration in neonatal compared with adult myocytes. This new model can therefore be used for testing hypotheses and obtaining a better quantitative understanding of differences between neonatal and adult physiology.


Single gallium nitride nanowire lasers.
There is much current interest in the optical properties of semiconductor nanowires, because the cylindrical geometry and strong two-dimensional confinement of electrons, holes and photons make them particularly attractive as potential building blocks for nanoscale electronics and optoelectronic devices, including lasersand nonlinear optical frequency converters. Gallium nitride (GaN) is a wide-bandgap semiconductor of much practical interest, because it is widely used in electrically pumped ultraviolet-blue light-emitting diodes, lasers and photodetectors. Recent progress in microfabrication techniques has allowed stimulated emission to be observed from a variety of GaN microstructures and films. Here we report the observation of ultraviolet-blue laser action in single monocrystalline GaN nanowires, using both near-field and far-field optical microscopy to characterize the waveguide mode structure and spectral properties of the radiation at room temperature. The optical microscope images reveal radiation patterns that correlate with axial Fabry-Perot modes (Q approximately 10(3)) observed in the laser spectrum, which result from the cylindrical cavity geometry of the monocrystalline nanowires. A redshift that is strongly dependent on pump power (45 meV microJ x cm(-2)) supports the idea that the electron-hole plasma mechanism is primarily responsible for the gain at room temperature. This study is a considerable advance towards the realization of electron-injected, nanowire-based ultraviolet-blue coherent light sources.