Statistical primer: checking model assumptions with regression diagnostics.
Regression modelling is an important statistical tool frequently utilized by cardiothoracic surgeons. However, these models-including linear, logistic and Cox proportional hazards regression-rely on certain assumptions. If these assumptions are violated, then a very cautious interpretation of the fitted model should be taken. Here, we discuss several assumptions and report diagnostics that can be used to detect departures from these assumptions. Most of the diagnostics discussed are based on residuals: a measure of the difference between the observed and model fitted values. Reliable and generalizable results depend on correctly developed statistical models, and proper diagnostics should play an integral part in the model development.


Reverse Shoulder Arthroplasty for the Treatment of 3 and 4- Part Fractures of the Humeral Head in the Elderly.
Proximal humeral fractures in elderly patients present with severe comminution and osteoporotic bone quality. Reverse shoulder arthroplasty has lately been proven beneficial in treating patients with complex proximal humeral fractures. The above technique is recommended and has better results in elderly than in younger individuals. We performed a literature search in the databases Pubmed, Medline, EMBASE and Cochrane Library for published articles between 1970 and 2016 using the terms: proximal humerus fractures and reverse shoulder arthroplasty. Significant benefits with the use of reverse prosthesis, especially in patients older than 70 years with a proximal humeral fracture, include reduced rehabilitation time as well as conservation of a fixed fulcrum for deltoid action in case of rotator cuff failure. Compared with hemiarthroplasty and internal fixation, reverse prosthesis may be particularly useful and give superior outcomes in older patients, due to comminuted fractures in osteopenic bones. However, significant disadvantages of this technique are potential complications and a demanding learning curve.Therefore, trained surgeons should follow specific indications when applying the particular treatment of proximal humeral fractures and be familiar with the surgical technique. Although long-term results and randomized studies for reverse prosthesis are lacking, short and mid- term outcomes have given promising results encouraging more shoulder surgeons to use this type of prosthesis in proximal humeral fractures.


A consensus approach toward the standardization of back pain definitions for use in prevalence studies.
A modified Delphi study conducted with 28 experts in back pain research from 12 countries. To identify standardized definitions of low back pain that could be consistently used by investigators in prevalence studies to provide comparable data. Differences in the definition of back pain prevalence in population studies lead to heterogeneity in study findings, and limitations or impossibilities in comparing or summarizing prevalence figures from different studies. Back pain definitions were identified from 51 articles reporting population-based prevalence studies, and dissected into 77 items documenting 7 elements. These items were submitted to a panel of experts for rating and reduction, in 3 rounds (participation: 76%). Preliminary results were presented and discussed during the Amsterdam Forum VIII for Primary Care Research on Low Back Pain, compared with scientific evidence and confirmed and fine-tuned by the panel in a fourth round and the preparation of the current article. Two definitions were agreed on a minimal definition (with 1 question covering site of low back pain, symptoms observed, and time frame of the measure, and a second question on severity of low back pain) and an optimal definition that is made from the minimal definition and add-ons (covering frequency and duration of symptoms, an additional measure of severity, sciatica, and exclusions) that can be adapted to different needs. These definitions provide standards that may improve future comparisons of low back pain prevalence figures by person, place and time characteristics, and offer opportunities for statistical summaries.


Plasma norepinephrine variations with dietary sodium intake.
Plasma catecholamine and renin activity levels were measured across a range of dietary sodium intakes (10--300 mEq/day) in 20 normal male volunteers. Supine plasma norepinephrine levels presented a triphasic pattern in relation to urine sodium, whereas epinephrine levels were not significantly altered by sodium intake, and renin showed the well-known hyperbolic relationship to urine sodium excretion. Highest supine norepinephrine values occurred at low salt intakes, the lowest when sodium excretion was between 100 and 180 mEq/day, and intermediate when sodium excretion was greater than 180 mEq/day. These findings show that sodium intake is an important consideration in the interpretation of plasma norepinephrine levels.


A high-throughput assay for rapid and simultaneous analysis of perfect markers for important quality and agronomic traits in rice using multiplexed MALDI-TOF mass spectrometry.
The application of single nucleotide polymorphisms (SNPs) in plant breeding involves the analysis of a large number of samples, and therefore requires rapid, inexpensive and highly automated multiplex methods to genotype the sequence variants. We have optimized a high-throughput multiplexed SNP assay for eight polymorphisms which explain two agronomic and three grain quality traits in rice. Gene fragments coding for the agronomic traits plant height (semi-dwarf, sd-1) and blast disease resistance (Pi-ta) and the quality traits amylose content (waxy), gelatinization temperature (alk) and fragrance (fgr) were amplified in a multiplex polymerase chain reaction. A single base extension reaction carried out at the polymorphism responsible for each of these phenotypes within these genes generated extension products which were quantified by a matrix-assisted laser desorption ionization-time of flight system. The assay detects both SNPs and indels and is co-dominant, simultaneously detecting both homozygous and heterozygous samples in a multiplex system. This assay analyses eight functional polymorphisms in one 5 microL reaction, demonstrating the high-throughput and cost-effective capability of this system. At this conservative level of multiplexing, 3072 assays can be performed in a single 384-well microtitre plate, allowing the rapid production of valuable information for selection in rice breeding.


Simultaneous detection of the seven main tomato-infecting RNA viruses by two multiplex reverse transcription polymerase chain reactions.
Cucumber mosaic virus, Tomato spotted wilt virus, Tomato mosaic virus, Tomato chlorosis virus, Pepino mosaic virus, Torrado tomato virus and Tomato infectious chlorosis virus cause serious damage and significant economic losses in tomato crops worldwide. The early detection of these pathogens is essential for preventing the viruses from spreading and improving their control. In this study, a procedure based on two multiplex RT-PCRs was developed for the sensitive and reliable detection of these seven viruses. Serial dilutions of positive controls were analysed by this methodology, and the results were compared with those obtained by ELISA and singleplex versions of RT-PCR. The multiplex and singleplex RT-PCR assays were able to detect specific targets at the same dilution and were 100 times more sensitive than ELISA. The multiplex versions were able to detect composite samples containing different concentrations of specific targets at ratios from 1:1 to 1:1000. In addition, 45 symptomatic tomato samples collected in different tomato-growing areas of Sicily (Italy) were analysed by multiplex RT-PCR, singleplex RT-PCR and commercially available ELISA tests. Similar results were obtained using the RT-PCR techniques, with a higher sensitivity than ELISA, revealing a common occurrence of mixed infections and confirming the presence of these seven virus species in Italy.


Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension.
The effect of decompressive craniectomy on clinical outcomes in patients with refractory traumatic intracranial hypertension remains unclear. From 2004 through 2014, we randomly assigned 408 patients, 10 to 65 years of age, with traumatic brain injury and refractory elevated intracranial pressure (>25 mm Hg) to undergo decompressive craniectomy or receive ongoing medical care. The primary outcome was the rating on the Extended Glasgow Outcome Scale (GOS-E) (an 8-point scale, ranging from death to "upper good recovery" [no injury-related problems]) at 6 months. The primary-outcome measure was analyzed with an ordinal method based on the proportional-odds model. If the model was rejected, that would indicate a significant difference in the GOS-E distribution, and results would be reported descriptively. The GOS-E distribution differed between the two groups (P<0.001). The proportional-odds assumption was rejected, and therefore results are reported descriptively. At 6 months, the GOS-E distributions were as follows: death, 26.9% among 201 patients in the surgical group versus 48.9% among 188 patients in the medical group; vegetative state, 8.5% versus 2.1%; lower severe disability (dependent on others for care), 21.9% versus 14.4%; upper severe disability (independent at home), 15.4% versus 8.0%; moderate disability, 23.4% versus 19.7%; and good recovery, 4.0% versus 6.9%. At 12 months, the GOS-E distributions were as follows: death, 30.4% among 194 surgical patients versus 52.0% among 179 medical patients; vegetative state, 6.2% versus 1.7%; lower severe disability, 18.0% versus 14.0%; upper severe disability, 13.4% versus 3.9%; moderate disability, 22.2% versus 20.1%; and good recovery, 9.8% versus 8.4%. Surgical patients had fewer hours than medical patients with intracranial pressure above 25 mm Hg after randomization (median, 5.0 vs. 17.0 hours; P<0.001) but had a higher rate of adverse events (16.3% vs. 9.2%, P=0.03). At 6 months, decompressive craniectomy in patients with traumatic brain injury and refractory intracranial hypertension resulted in lower mortality and higher rates of vegetative state, lower severe disability, and upper severe disability than medical care. The rates of moderate disability and good recovery were similar in the two groups. (Funded by the Medical Research Council and others; RESCUEicp Current Controlled Trials number, ISRCTN66202560 .).


An Item Bank for Abuse of Prescription Pain Medication from the Patient-Reported Outcomes Measurement Information System (PROMIS®).
There is a need to monitor patients receiving prescription opioids to detect possible signs of abuse. To address this need, we developed and calibrated an item bank for severity of abuse of prescription pain medication as part of the Patient-Reported Outcomes Measurement Information System (PROMIS ® ). Comprehensive literature searches yielded an initial bank of 5,310 items relevant to substance use and abuse, including abuse of prescription pain medication, from over 80 unique instruments. After qualitative item analysis (i.e., focus groups, cognitive interviewing, expert review, and item revision), 25 items for abuse of prescribed pain medication were included in field testing. Items were written in a first-person, past-tense format, with a three-month time frame and five response options reflecting frequency or severity. The calibration sample included 448 respondents, 367 from the general population (ascertained through an internet panel) and 81 from community treatment programs participating in the National Drug Abuse Treatment Clinical Trials Network. A final bank of 22 items was calibrated using the two-parameter graded response model from item response theory. A seven-item static short form was also developed. The test information curve showed that the PROMIS ® item bank for abuse of prescription pain medication provided substantial information in a broad range of severity. The initial psychometric characteristics of the item bank support its use as a computerized adaptive test or short form, with either version providing a brief, precise, and efficient measure relevant to both clinical and community samples.


Sequential grouping of pure-tone percepts evoked by the segregation of components from a complex tone.
A sudden change applied to a single component can cause its segregation from an ongoing complex tone as a pure-tone-like percept. Three experiments examined whether such pure-tone-like percepts are organized into streams by extending the research of Bregman and Rudnicky (1975). Those authors found that listeners struggled to identify the presentation order of 2 pure-tone targets of different frequency when they were flanked by 2 lower frequency "distractors." Adding a series of matched-frequency "captor" tones, however, improved performance by pulling the distractors into a separate stream from the targets. In the current study, sequences of discrete pure tones were substituted by sequences of brief changes applied to an otherwise constant 1.2-s complex tone. Pure-tone-like percepts were evoked by applying 6-dB increments to individual components of a complex comprising harmonics 1-7 of 300 Hz (Experiment 1) or 0.5-ms changes in interaural time difference to individual components of a log-spaced complex (range 160-905 Hz; Experiment 2). Results were consistent with the earlier study, providing clear evidence that pure-tone-like percepts are organized into streams. Experiment 3 adapted Experiment 1 by presenting a global amplitude increment either synchronous with, or just after, the last captor prior to the 1st distractor. In the former case, for which there was no pure-tone-like percept corresponding to that captor, the captor sequence did not aid performance to the same extent as previously. It is concluded that this change to the captor-tone stream partially resets the stream-formation process, and so the distractors and targets became likely to integrate once more.


Altered Functional Connectivity Strength in Abstinent Chronic Cocaine Smokers Compared to Healthy Controls.
Past research involving cocaine and resting-state functional connectivity (RSFC) has shown altered functional connectivity within the frontal and between the frontal and other cortical and subcortical brain regions in chronic users of cocaine. However, there have been discrepancies in literature regarding the relationship between RSFC between brain regions and cocaine use behavior. This study explored the RSFC between brain regions in cocaine smokers abstinent from cocaine use for 72 h and healthy controls. Also, the relationship between RSFC between brain regions and various cocaine use measures (cocaine use duration; frequency, and money spent on cocaine/week) was examined. Twenty chronic cocaine users and 17 controls completed a resting-state scan and an anatomical MPRAGE scan. Group independent component analysis performed on functional magnetic resonance imaging data identified 13 ICs pertaining to distinct resting-state networks, and group-level differences were examined. To examine inter-network functional connectivity between brain regions, these 13 ICs were divided into 61 distinct regions of interest (ROIs). Correlations were calculated between 61 ROI time series. For the ROI pairs that significantly differed from controls in connectivity strength, correlations were computed between connectivity strength and cocaine use measures. Results showed an enhanced RSFC within the sensory motor cortex and the left frontal-parietal network in cocaine users than controls. An increased inter-network RSFC between frontal-temporal and frontal-parietal brain regions, and a decreased RSFC between parietal-parietal, occipital-limbic, occipital-occipital, and occipital-parietal brain regions was found in cocaine users. This study demonstrated that intra-network connectivity strength of sensory motor cortex was negatively correlated with years of cocaine use. Inter-network connectivity strength between occipital-limbic brain regions was positively correlated with years of cocaine use, while connectivity strength within occipital brain regions was negatively related to cocaine use frequency and money spent on cocaine per week in abstinent cocaine users.


Photopigments and photoentrainment in the Syrian golden hamster.
The Syrian golden hamster (Mesocricetus auratus) is an important model in the study of circadian rhythms. However, as in other mammals, little is known about the photoreceptors that mediate circadian entrainment. Using immunocytochemistry and RNA blot hybridization, we found no evidence for the presence of blue-/UV-sensitive opsin. In contrast, green-sensitive cone opsin was demonstrated in the retina both by immunocytochemistry and reverse-transcription PCR. When used as a probe in RNA blot hybridization, this PCR fragment labelled one transcript (5.8 kb) in hamster retinal RNA. These findings are in accordance with preliminary data from other investigators using electroretinography, which showed one cone-mediated photoreceptive mechanism with a maximum sensitivity of 501 nm, but none at shorter wavelengths. However, we found that non-saturating pulses of ultraviolet radiation (357 nm) caused phase shifts in locomotor behaviour. These results corroborate earlier reports that UV radiation can regulate the photoperiodic response in this animal. Having confirmed these apparently contradictory earlier reports, we discuss the mechanisms that might create a UV-triggered non-visual response in a green cone monochromat. Finally, we propose the use of the Syrian golden hamster as a model for photoreceptor development and function in the absence of S/UV cones.


Lifestyle behaviours and quality-adjusted life years in middle and older age.
to examine the relationship between combined lifestyle behaviours and quality-adjusted life years (QALYs) in a general population. a population-based study was conducted in 13,358 men and women who participated in the European Prospective Investigation into Cancer (EPIC)-Norfolk (baseline 1993-97). A score of 1 was given to each of non-smoking, physically not inactive, moderate alcohol consumption (1-14 units) and consumption of at least five portions of fruit and vegetables (vitamin C level ≥50 µmol/l). Short-Form Six-Dimension (SF-6D) health utility index scores were derived from the SF-36. QALYs were estimated up to follow-up (July 2007). a total of 13,358 men and women were eligible to be included in the study (aged 40-79 years at baseline). A total of 12,921 people were alive at follow-up (117, 784 person-years). Mean follow-up period was ∼11.5 years. 437 (4.4% of men and 2.4% of women) died. The death rate was 6.5 times higher in people with health behaviour score 0 compared with those who scored 4 (8.4 versus 1.3%). People with higher scores had significantly higher QALYs. our findings support the view that modifiable lifestyle factors are an important component in health improvement.


Hepatotoxicity After Immune Checkpoint Inhibitor Therapy in Melanoma: Natural Progression and Management.
To report the clinical features, treatment, and outcomes of patients with immune checkpoint inhibitor-induced hepatotoxicity. In this retrospective observational study, we identified patients with metastatic malignant melanoma seen in consultation and/or treated between March 2011 and March 2016. Hepatotoxicity was assessed using the Common Terminology Criteria for Adverse Events, v4.0. Seventeen patients were identified as having any degree of hepatotoxicity by history (grade 1 to 4). Twelve of 17 were diagnosed after ipilimumab, 3 of 17 were diagnosed after pembrolizumab, and 2 of 17 after ipilimumab combined with nivolumab. Median time from first dose of immune therapy to hepatotoxicity was 52 days. Clinical symptoms were variable: asymptomatic, fatigue, myalgias, headache, abdominal pain, nausea, vomiting, confusion, and/or jaundice. Eight patients had concurrent adverse events including colitis, hypophysitis, pneumonitis, and/or rash. Immune therapy was discontinued in all patients except 3. The patients were most commonly treated with systemic corticosteroids such as prednisone. Immunosuppression was discontinued by taper over a median of 42 days; in 3 patients steroids had to be reinitiated based on clinical or laboratory worsening of liver tests. Normalization of liver tests was seen within a median of 31 days of immunosuppression initiation. One patient with grade 4 hepatotoxicity had normalization with the addition of cyclosporine. Melanoma patients treated with immune checkpoint inhibitors should be monitored regularly for hepatotoxicity. Treatment with discontinuation of therapy and initiation of corticosteroids is indicated with grade 3 or 4 hepatotoxicity. Cyclosporine may be beneficial in steroid-refractory hepatotoxicity.


Perceived factors in return to work after acquired brain injury: A qualitative meta-synthesis.
A substantial proportion of survivors after brain injuries originating from trauma, tumour, or stroke may experience reduced ability to work due to a number of challenges. The purpose of this review is to summarize and highlight factors that have been perceived and reported as important in order to return to work after an acquired brain injury. A qualitative ethnographic meta-synthesis is used to interpret and develop concepts from studies retrieved from systematic searches in the electronic databases PubMed, PsycINFO, and ISI Web of Science. A total of 16 studies were included in the meta-synthesis. Four key concepts were identified as important for return to work after an acquired brain injury: empowerment, self-awareness, motivation, and facilitation. The results of the meta-synthesis indicate that personal development is experienced as essential in order to return to work after an acquired brain injury, involving identification of each individual's strengths and weaknesses. These personal factors intersect with an emphasis of the employer providing a certain degree of facilitation in the workplace. All of these aspects will affect one's motivation to return to work and can therefore be crucial to succeed.


Is the Association Between Early Childhood Screen Media Use and Effortful Control Bidirectional? A Prospective Study During the COVID-19 Pandemic.
Individual differences in effortful control, a component of temperament, reflecting the ability to use attention and other cognitive processes to self-regulate emotion and behavior, contribute to child academic adjustment, social competence, and wellbeing. Research has linked excessive screen time in early childhood to reduced self-regulation ability. Furthermore, research suggests that parents are more likely to use screens with children who have more challenging temperaments, such as low levels of effortful control. Since screen time by children between the ages of 0 and 18 has increased during the COVID-19 pandemic, it remains timely to investigate the developmental pattern of association between child screen media use and effortful control. We hypothesize that higher levels of screen media intake at age 3.5 will be associated with lower effortful control at age 4.5 and that lower effortful control at 3.5 will contribute to more screen media intake at age 4.5. This study draws on participants followed longitudinally over the span of 2-years for an investigation of Canadian preschoolers' screen media use during the pandemic (N = 316, Wave 1). A follow-up with this sample was completed in 2021 (N = 265, Wave 2). Analyses using a cross-lagged panel model revealed stability in child screen time and effortful control between the ages of 3.5 and 4.5. Child screen time at age 3.5 significantly contributed to decreased effortful control scores at the age of 4.5, whereas effortful control at age 3.5 did not contribute to screen time at age 4.5. Our results partially confirmed our hypothesis and indicated that higher levels of screen time intake were detrimental to the development of effortful control. These results suggest that screen media use, an exceedingly frequent activity, may play an enduring role in development by shaping young children's temperaments.


Response of Pasteurella haemolytica to erythromycin and dexamethasone in calves with established infection.
A subcutaneous soft tissue infection model in calves was used to study the in vivo response of Pasteurella haemolytica to erythromycin and dexamethasone. Two tissue chambers were implanted SC in each of 12 calves. At 45 days after implantation, all tissue chambers were inoculated with an erythromycin-sensitive strain of P haemolytica. Starting 24 hours after inoculation, calves were allotted to 4 groups of equal size and a 2 x 2-factorial arrangement of treatments was applied: 3 calves were given erythromycin (30 mg/kg of body weight, IM, for 5 days), 3 calves were given dexamethasone (0.05 mg/kg, IM, for 2 days), 3 calves were given erythromycin and dexamethasone, and the remaining calves served as nontreated controls. Chamber fluids were tested daily, and the response to treatment was measured. Neither erythromycin nor dexamethasone affected viability or growth of bacteria within tissue chambers. Dexamethasone had no effect on the influx of neutrophils into infected chambers. Despite repeated administration of a high dose of erythromycin and attainment of adequate concentration in serum, erythromycin concentration in chamber fluids did not exceed the minimal inhibitory concentration established in vitro. These results indicate that the clinical efficacy of erythromycin against P haemolytica sequestered in consolidated pneumonic lesions may not be well correlated with predictions based on serum pharmacokinetic and in vitro susceptibility data.


Widening the mutation spectrum of EVC and EVC2: ectopic expression of Weyer variants in NIH 3T3 fibroblasts disrupts Hedgehog signaling.
Autosomal recessive Ellis-van Creveld syndrome and autosomal dominant Weyer acrodental dysostosis are allelic conditions caused by mutations in EVC or EVC2. We performed a mutation screening study in 36 EvC cases and 3 cases of Weyer acrodental dysostosis, and identified pathogenic changes either in EVC or in EVC2 in all cases. We detected 40 independent EVC/EVC2 mutations of which 29 were novel changes in Ellis-van Creveld cases and 2 were novel mutations identified in Weyer pedigrees. Of interest one EvC patient had a T>G nucleotide substitution in intron 7 of EVC (c.940-150T>G), which creates a new donor splice site and results in the inclusion of a new exon. The T>G substitution is at nucleotide +5 of the novel 5' splice site. The three Weyer mutations occurred in the final exon of EVC2 (exon 22), suggesting that specific residues encoded by this exon are a key part of the protein. Using murine versions of EVC2 exon 22 mutations we demonstrate that the expression of a Weyer variant, but not the expression of a truncated protein that mimics an Ellis-van Creveld syndrome mutation, impairs Hedgehog signal transduction in NIH 3T3 cells in keeping with its dominant effect.


Protein kinases, from B to C.
The PKB (protein kinase B) and PKC (protein kinase C) families display highly related catalytic domains that require a largely conserved series of phosphorylations for the expression of their optimum activities. However, in cells, the dynamics of these modifications are quite distinct. Based on experimental evidence, it is argued that the underlying mechanisms determining these divergent behaviours relate to the very different manner in which their variant regulatory domains interact with their respective catalytic domains. It is concluded that the distinct behaviours of PKB and PKC proteins are defined by the typical ground states of these proteins.


Northern hemisphere glaciation during the globally warm early Late Pliocene.
The early Late Pliocene (3.6 to ∼3.0 million years ago) is the last extended interval in Earth's history when atmospheric CO2 concentrations were comparable to today's and global climate was warmer. Yet a severe global glaciation during marine isotope stage (MIS) M2 interrupted this phase of global warmth ∼3.30 million years ago, and is seen as a premature attempt of the climate system to establish an ice-age world. Here we propose a conceptual model for the glaciation and deglaciation of MIS M2 based on geochemical and palynological records from five marine sediment cores along a Caribbean to eastern North Atlantic transect. Our records show that increased Pacific-to-Atlantic flow via the Central American Seaway weakened the North Atlantic Current and attendant northward heat transport prior to MIS M2. The consequent cooling of the northern high latitude oceans permitted expansion of the continental ice sheets during MIS M2, despite near-modern atmospheric CO2 concentrations. Sea level drop during this glaciation halted the inflow of Pacific water to the Atlantic via the Central American Seaway, allowing the build-up of a Caribbean Warm Pool. Once this warm pool was large enough, the Gulf Stream-North Atlantic Current system was reinvigorated, leading to significant northward heat transport that terminated the glaciation. Before and after MIS M2, heat transport via the North Atlantic Current was crucial in maintaining warm climates comparable to those predicted for the end of this century.


The mental well-being and coping strategies of Canadian adolescents during the COVID-19 pandemic: a qualitative, cross-sectional study.
Qualitative research is lacking on the mental well-being of adolescents during the COVID-19 pandemic. The aim of this study was to explore the feelings and emotions adolescents experienced during the first wave of the COVID-19 pandemic and the coping strategies they identified and employed to manage those emotions. Participants living in Canada aged 13-19 years were recruited through social media platforms and youth-serving organizations. Qualitative data were gathered from 2 open-ended questions included in a youth-informed cross-sectional online survey: "What feelings and emotions have you experienced around the pandemic?" and "What coping strategies have you used during the pandemic?" We collected data from June 2020 to September 2020. A summative content analysis was undertaken to analyze survey responses inductively. A total of 1164 open-ended responses from Canadian adolescents (n = 851; mean age 15.6, standard deviation 1.7, yr) were analyzed. We identified 3 major themes within the category of feelings and emotions associated with the pandemic: sociospatial and temporal disconnections, emotional toll of the pandemic and positives amid the pandemic. Within the category of coping strategies used during the pandemic, 2 major themes were identified: connecting online and outdoors, and leisure and health-promoting activities. Although the emotional toll of the first wave of the COVID-19 pandemic is evident, participants in our study adopted various positive coping strategies to mitigate their distress, including physical activity, safe peer interactions and hobbies. The results have important implications for public health policy and practice during pandemic times, emphasizing the importance of accessible mental health resources for those experiencing psychological distress.


Feasibility and acceptability of ACT for the community case management of malaria in urban settings in five African sites.
The community case management of malaria (CCMm) is now an established route for distribution of artemisinin-based combination therapy (ACT) in rural areas, but the feasibility and acceptability of the approach through community medicine distributors (CMD) in urban areas has not been explored. It is estimated that in 15 years time 50% of the African population will live in urban areas and transmission of the malaria parasite occurs in these densely populated areas. Pre- and post-implementation studies were conducted in five African cities: Ghana, Burkina Faso, Ethiopia and Malawi. CMDs were trained to educate caregivers, diagnose and treat malaria cases in < 5-year olds with ACT. Household surveys, focus group discussions and in-depth interviews were used to evaluate impact. Qualitative findings: In all sites, interviews revealed that caregivers' knowledge of malaria signs and symptoms improved after the intervention. Preference for CMDs as preferred providers for malaria increased in all sites.Quantitative findings: 9001 children with an episode of fever were treated by 199 CMDs in the five study sites. Results from the CHWs registers show that of these, 6974 were treated with an ACT and 6933 (99%) were prescribed the correct dose for their age. Fifty-four percent of the 3,025 children for which information about the promptness of treatment was available were treated within 24 hours from the onset of symptoms.From the household survey 3700 children were identified who had an episode of fever during the preceding two weeks. 1480 (40%) of them sought treatment from a CMD and 1213 of them (82%) had received an ACT. Of these, 1123 (92.6%) were administered the ACT for the correct number of doses and days; 773 of the 1118 (69.1%) children for which information about the promptness of treatment was available were treated within 24 hours from onset of symptoms, and 768 (68.7%) were treated promptly and correctly. The concept of CCMm in an urban environment was positive, and caregivers were generally satisfied with the services. Quality of services delivered by CMDs and adherence by caregivers are similar to those seen in rural CCMm settings. The proportion of cases seen by CMDs, however, tended to be lower than was generally seen in rural CCMm. Urban CCMm is feasible, but it struggles against other sources of established healthcare providers. Innovation is required by everyone to make it viable.


Depression in patients with Parkinsonism.
Forty-five patients with parkinsonism were carefully matched for age and sex with 45 chronically disabled control patients with a significantly more severe grade of physical handicap. Depression was measured by the Hamilton Rating Scale, and it was found that the parkinsonian group was very significantly more depressed than the control group (p less than 0-0001). Depression scores in both groups were unaffected by the patients's sex or by the severity of the disability. Analysis of the individual ratings of the Hamilton Scale showed that parkinsonian patients had significantly higher scores on items relating to suicide, work and interests, retardation, psychic anxiety, general somatic symptoms, and loss of insight. It was concluded that patients with parkinsonism suffer a degree of depression which cannot be solely a reaction to the stress of physical disability. This finding is discussed with reference to the monoamine hypothesis of depressive illness.


Organizational effects of fetal testosterone on human corpus callosum size and asymmetry.
Previous theory and research in animals has identified the critical role that fetal testosterone (FT) plays in organizing sexually dimorphic brain development. However, to date there are no studies in humans directly testing the organizational effects of FT on structural brain development. In the current study we investigated the effects of FT on corpus callosum size and asymmetry. High-resolution structural magnetic resonance images (MRI) of the brain were obtained on 28 8-11-year-old boys whose exposure to FT had been previously measured in utero via amniocentesis conducted during the second trimester. Although there was no relationship between FT and midsaggital corpus callosum size, increasing FT was significantly related to increasing rightward asymmetry (e.g., Right>Left) of a posterior subsection of the callosum, the isthmus, that projects mainly to parietal and superior temporal areas. This potential organizational effect of FT on rightward callosal asymmetry may be working through enhancing the neuroprotective effects of FT and result in an asymmetric distribution of callosal axons. We suggest that this possible organizational effect of FT on callosal asymmetry may also play a role in shaping sexual dimorphism in functional and structural brain development, cognition, and behavior.


Lack of Association Between Interleukin 28B Polymorphism and Vertical Transmission of Hepatitis C.
Single genetic nucleotide polymorphism (rs12979860) near the gene for interleukin 28B (IL28B) is known to be of importance for frequency of spontaneous clearance and treatment outcome in interferon-based therapies in patients with hepatitis C virus (HCV) infection. The aim of the present study was to investigate whether IL28B polymorphism in children and/or their mothers plays a role in vertical transmission of HCV (HCV-VT). Plasma samples from 59 infected women, 76 uninfected children born to infected mothers, and 47 children with known vertically transmitted HCV infection, were analysed for IL28B polymorphism and classified by the IL28B genotype (C/C, C/T, and T/T) and by viral genotype. The proportion of children with genotype C/C was the same in the vertically infected (36%, 17/47) and the exposed uninfected children (38%, 29/76). No difference was seen when stratifying for viral genotype. There was no association between mothers' IL28B genotype and the risk of vertical transmission. Regardless of viral genotype we found no association between IL28B genotype and the risk of HCV-VT. The IL28B genotype CC, which has been shown to be favourable in other settings, was not protective of HCV-VT. Thus, other factors possibly associated with the risk of HCV-VT need to be explored.


Mobile Apps for Health Behavior Change: Protocol for a Systematic Review.
The popularity and ubiquity of mobile apps have rapidly expanded in the past decade. With a growing focus on patient interaction with health management, mobile apps are increasingly used to monitor health and deliver behavioral interventions. The considerable variation in these mobile health apps, from their target patient group to their health behavior, and their behavioral change strategy, has resulted in a large but incohesive body of literature. The purpose of this protocol is to provide an overview of the current landscape, theories behind, and effectiveness of mobile apps for health behavior change. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols will be used to structure this protocol. The focus of the systematic review is guided by a population, intervention, comparator, and outcome framework. A systematic search of Medline, EMBASE, CINAHL, and Web of Science will be conducted. Two authors will independently screen the titles and abstracts of identified references and select studies according to the eligibility criteria. Any discrepancies will then be discussed and resolved. One reviewer will extract data into a standardized form, which will be validated by a second reviewer. Risk of bias was assessed using the Cochrane Collaboration Risk of Bias tool, and a descriptive analysis will summarize the effectiveness of all the apps. As of November 2019, the systematic review has been completed and is in peer review for publication. This systematic review will summarize the current mobile app technologies and their effectiveness, usability, and coherence with behavior change theory. It will identify areas of improvement (where there is no evidence of efficacy) and help inform the development of more useful and engaging mobile health apps. PROSPERO CRD42019155604; https://tinyurl.com/sno4lcu. PRR1-10.2196/16931.


Malnutrition treatment to become a core competency.
The International Pediatric Association has resolved that the identification and treatment of severe malnutrition should be a core competency for paediatricians and related health professionals worldwide. The Resolution is in response to the urgent need to reduce deaths and disability among young children. The Resolution has implications for the training of doctors, nurses and other health workers as current curricula are often insufficient to confer competency. Results of a survey of national paediatric societies suggest that training institutions need assistance in teaching about malnutrition treatment. Formation of national multidisciplinary teams for advocacy, strategic planning and action are proposed and it is anticipated that paediatricians will play a major role.


Empirical prediction of peptide octanol-water partition coefficients.
Peptides are of great therapeutic potential as vaccines and drugs. Knowledge of physicochemical descriptors, including the partition coefficient P (commonly expressed in logarithm form: logP), is useful for screening out unsuitable molecules and also for the development of predictive Quantitative Structure-Activity Relationships (QSARs). In this paper we develop a new approach to the prediction of LogP values for peptides based on an empirical relationship between global molecular properties and measured physical properties. Our method was successful in terms of peptide prediction (total r(2) = 0.641). The final model consisted of 5 physicochemical descriptors (molecular weight, number of single bonds, 2D-VDW volume, 2D-VSA hydrophobic and 2D-VSA polar). The approach is peptide specific and its predictive accuracy was high. Overall, 67% of the peptides were able to be predicted within +/-0.5 log units from the experimental values. Our method thus represents a novel prediction method with proven predictive ability.


A slowly enlarging mass on the finger.
An otherwise healthy 71-year-old woman presented with an asymptomatic mass on her right 4th finger that had been slowly enlarging over the past 2 years. On physical examination, there was a tan-pink, freely mobile, rubbery 9-mm papule with a central keratotic plug located over the extensor aspect of the proximal interphalangeal joint of the right 4th finger. A 3-mm punch biopsy of the lesion was performed. Histopathologic findings were consistent with a diagnosis of aggressive digital papillary adenocarcinoma (ADPAca), an adnexal tumor with high metastatic potential that is unfortunately commonly misdiagnosed owing to its rarity and nondescript appearance. Aggressive surgical treatment including radical excision or digital amputation with or without sentinel lymph node biopsy is advocated in the treatment of ADPAca.


Black soybean extract improves lipid profiles in fenofibrate-treated type 2 diabetics with postprandial hyperlipidemia.
Black soybeans (Glycine max (L.) Merr.) are known to be rich in polyphenols, including anthocyanins, and they have been consumed since ancient times for their beneficial effects on health. In addition, it has been reported that black soybean (BS) seed coat may ameliorate obesity and insulin resistance. In the present study, we administered BS extract to type 2 diabetics for 2 months to investigate the effects of BS on glycemic control and lipid metabolism parameters. In addition, we administered BS and antihyperlipidemic agent, fenofibrate, to patients with type 2 diabetes complicated by postprandial hyperlipidemia for 2 months and assessed the combined effects of fenofibrate and BS on serum lipid profile. The results showed that administration of the BS alone had no effect on the blood glucose or lipid levels, but that administration of fenofibrate alone and fenofibrate in combination with the BS significantly lowered their serum triglyceride (TG) level at fasting state, and the percent decrease in the serum TG level after combined administration was significantly higher than in the subjects who received fenofibrate alone. Furthermore, the serum LDL cholesterol concentration, which did not decrease when fenofibrate was administered alone, decreased significantly when the BS and fenofibrate were administered in combination. These results suggest that combined administration of the BS with fenofibrate enhanced the antihyperlipidemic action of fenofibrate, and the results of this study demonstrated the usefulness of the BS in clinical practice.


Melatonin stimulates the release of growth hormone and prolactin by a possible induction of the expression of frog growth hormone-releasing peptide and its related peptide-2 in the amphibian hypothalamus.
We recently identified a novel hypothalamic neuropeptide stimulating GH release in bullfrogs and termed it frog GH-releasing peptide (fGRP). The fGRP precursor encodes fGRP and its related peptides (fGRP-RP-1, -RP-2, and -RP-3), and fGRP-RP-2 also stimulates GH and prolactin (PRL) release. Cell bodies and terminals containing these neuropeptides are localized in the suprachiasmatic nucleus (SCN) and median eminence, respectively. To understand the physiological role of fGRP and fGRP-RP-2, we investigated the mechanisms that regulate the expression of these neuropeptides. This study shows that melatonin induces the expression of fGRP and fGRP-RPs in bullfrogs. Orbital enucleation combined with pinealectomy (Ex plus Px) decreased the expression of fGRP precursor mRNA and content of mature fGRP and fGRP-RPs in the diencephalon including the SCN and median eminence. Conversely, melatonin administration to Ex plus Px bullfrogs increased dose-dependently their expressions. The expression of fGRP precursor mRNA was photoperiodically controlled and increased under short-day photoperiods, when the nocturnal duration of melatonin secretion increases. To clarify the mode of melatonin action on the induction of fGRP and fGRP-RPs, we further demonstrated the expression of Mel(1b), a melatonin receptor subtype, in SCN neurons expressing fGRP precursor mRNA. Finally, we investigated circulating GH and PRL levels after melatonin manipulation because fGRP and fGRP-RP-2 stimulate the release of GH and GH/PRL, respectively. Ex plus Px decreased plasma GH and PRL concentrations, whereas melatonin administration increased these hormone levels. These results suggest that melatonin induces the expression of fGRP and fGRP-RP-2, thus stimulating the release of GH and PRL in bullfrogs.


High content image analysis for human H4 neuroglioma cells exposed to CuO nanoparticles.
High content screening (HCS)-based image analysis is becoming an important and widely used research tool. Capitalizing this technology, ample cellular information can be extracted from the high content cellular images. In this study, an automated, reliable and quantitative cellular image analysis system developed in house has been employed to quantify the toxic responses of human H4 neuroglioma cells exposed to metal oxide nanoparticles. This system has been proved to be an essential tool in our study. The cellular images of H4 neuroglioma cells exposed to different concentrations of CuO nanoparticles were sampled using IN Cell Analyzer 1000. A fully automated cellular image analysis system has been developed to perform the image analysis for cell viability. A multiple adaptive thresholding method was used to classify the pixels of the nuclei image into three classes: bright nuclei, dark nuclei, and background. During the development of our image analysis methodology, we have achieved the followings: (1) The Gaussian filtering with proper scale has been applied to the cellular images for generation of a local intensity maximum inside each nucleus; (2) a novel local intensity maxima detection method based on the gradient vector field has been established; and (3) a statistical model based splitting method was proposed to overcome the under segmentation problem. Computational results indicate that 95.9% nuclei can be detected and segmented correctly by the proposed image analysis system. The proposed automated image analysis system can effectively segment the images of human H4 neuroglioma cells exposed to CuO nanoparticles. The computational results confirmed our biological finding that human H4 neuroglioma cells had a dose-dependent toxic response to the insult of CuO nanoparticles.


Prevalence of Consumption of Smokeless Tobacco Products and Exposure to Second-Hand Smoke among Women in the Reproductive Age Group in a Rural Area of Koppal, Karnataka.
Tobacco use is one of the most important causes of death and disease globally. Nearly one-third of the population in India uses tobacco, and smokeless form is culturally acceptable even among women. (1) To estimate the prevalence of consumption of smokeless tobacco (SLT) products among women in the reproductive age group in the study setting. (2) To determine the various factors associated with the consumption of SLT. (3) To estimate the prevalence of exposure to second-hand smoke among the study participants. A cross-sectional study was conducted in the field area of primary health center Irkalgad, Koppal in March 2018. A cluster sampling technique was used and a total of 829 women were included. Data were collected using pretested and semi-structured questionnaire and analyzed using the Epi info software version 3.5.4 (Centers for Disease Control and Prevention" (CDC), Atlanta, Georgia, United States of America). The prevalence of consumption of SLT products was 17.85%, and the most common product consumed was tobacco with betel quid. Tobacco consumption was found to be significantly associated with age, literacy, marital, and employment status of the study participants. The present study concludes that SLT consumption is high among women in the reproductive age group in the study setting and identifies multiple determinants for effective planning of interventions.


Sunday Driver/JIP3 binds kinesin heavy chain directly and enhances its motility.
Neuronal development, function and repair critically depend on axonal transport of vesicles and protein complexes, which is mediated in part by the molecular motor kinesin-1. Adaptor proteins recruit kinesin-1 to vesicles via direct association with kinesin heavy chain (KHC), the force-generating component, or via the accessory light chain (KLC). Binding of adaptors to the motor is believed to engage the motor for microtubule-based transport. We report that the adaptor protein Sunday Driver (syd, also known as JIP3 or JSAP1) interacts directly with KHC, in addition to and independently of its known interaction with KLC. Using an in vitro motility assay, we show that syd activates KHC for transport and enhances its motility, increasing both KHC velocity and run length. syd binding to KHC is functional in neurons, as syd mutants that bind KHC but not KLC are transported to axons and dendrites similarly to wild-type syd. This transport does not rely on syd oligomerization with itself or other JIP family members. These results establish syd as a positive regulator of kinesin activity and motility.


Folate deficiency induces in vitro and mouse brain region-specific downregulation of leucine carboxyl methyltransferase-1 and protein phosphatase 2A B(alpha) subunit expression that correlate with enhanced tau phosphorylation.
Altered folate homeostasis is associated with many clinical and pathological manifestations in the CNS. Notably, folate-mediated one-carbon metabolism is essential for methyltransferase-dependent cellular methylation reactions. Biogenesis of protein phosphatase 2A (PP2A) holoenzyme containing the regulatory B(alpha) subunit, a major brain tau phosphatase, is controlled by methylation. Here, we show that folate deprivation in neuroblastoma cells induces downregulation of PP2A leucine carboxyl methyltransferase-1 (LCMT-1) expression, resulting in progressive accumulation of newly synthesized demethylated PP2A pools, concomitant loss of B(alpha), and ultimately cell death. These effects are further accentuated by overexpression of PP2A methylesterase (PME-1) but cannot be rescued by PME-1 knockdown. Overexpression of either LCMT-1 or B(alpha) is sufficient to protect cells against the accumulation of demethylated PP2A, increased tau phosphorylation, and cell death induced by folate starvation. Conversely, knockdown of either protein accelerates folate deficiency-evoked cell toxicity. Significantly, mice maintained for 2 months on low-folate or folate-deficient diets have brain-region-specific alterations in metabolites of the methylation pathway. Those are associated with downregulation of LCMT-1, methylated PP2A, and B(alpha) expression and enhanced tau phosphorylation in susceptible brain regions. Our studies provide novel mechanistic insights into the regulation of PP2A methylation and tau. They establish LCMT-1- and B(alpha)-containing PP2A holoenzymes as key mediators of the role of folate in the brain. Our results suggest that counteracting the neuronal loss of LCMT-1 and B(alpha) could be beneficial for all tauopathies and folate-dependent disorders of the CNS.


Effect of melittin on mice stomach.
Melittin, the main bee venom component, has many positive biological effects and a relatively low toxicity in various cell types. However, there is no evidence of the effect of melittin on gastrointestinal cells. In the present study, we investigated the histological and immuonohistochemical effects of melittin on mice stomach. Adult male mice (Albino Swiss) were randomly divided into two groups (7 mice for each group): control group and melittin only treated group (10 and 40 μg/kg). These mice were sacrificed, then samples from the stomach were collected and prepared for histopathological studies by using alcian blue stain and immuonohistochemical studies by using smooth muscle actin (SMA) antibody. Treatment with melittin alone do not cause any harmful effect on the stomach tissue where the microscopic examination of Alcian blue stained section showed the normal distribution of the mucous secreting cells of the stomach tissues. On other hand, no changes were observed on smooth muscle cells. This study demonstrated the safety of using melittin on gastrointestinal tissues if used in definite dose and for suitable duration, which offers an opportunity for its use as a treatment for many diseases of the gastrointestinal tract.


The effect of surgical timing on functional outcomes of traumatic facial nerve paralysis.
The optimal timing for surgical exploration of traumatic facial paralysis to best preserve facial function is currently controversial. This article reviews the final outcomes of facial function in patients with traumatic intratemporal facial nerve injury according to the timing of surgical exploration. We performed a retrospective review of 58 patients with complete facial nerve paralysis caused by temporal bone fractures as a result of head trauma between 1998 and 2007. Patients were divided into three groups according to the type of trauma. The only difference between patients in each group was the timing of the surgical exploration. Characteristics assessed in the study included type of trauma, location of facial nerve injury, timing of surgical intervention, audiometric findings, surgical approach, and long-term follow-up of recovery of facial nerve function, as assessed by two facial nerve grading systems. The final functional gains in early-operated patients were 3.7 +/- 0.59 on the House-Brackmann (HB) scale and 75.6 +/- 10.88 on the Sunnybrook scale. The outcome in late-operated patients was 2.17 +/- 0.52 on the HB scale and 34.7 +/- 16.95 on the Sunnybrook scale, and that of nonoperated patients was 2.0 +/- 0.63 on the HB scale and 26.8 +/- 6.27 on the Sunnybrook scale. This study demonstrated that some patients with traumatic facial nerve paralysis who had nerve conduction studies consistent with a poor prognosis regained considerable facial function after early surgical intervention. However, late exploration after facial nerve paralysis did not result in positive outcomes, regardless of the type of temporal bone fracture or the site of injury, and no difference was observed compared with conservative treatment.


Radiotherapy-induced myelosuppression in dogs: 103 cases (2002-2006).
Definitive radiotherapy refers to delivery of large doses, typically 48-62 Gray, of ionizing radiation over several weeks using a daily or alternate-day fractionation schedule. The impact of definitive radiotherapy alone on haematopoiesis in tumour-bearing dogs is unknown. Medical records from 103 dogs receiving definitive (60) Cobalt teletherapy for cancer over a 5-year period were reviewed for signalment, tumour type and location, total radiotherapy dose and fractionation scheme. Complete blood count data were collected before, halfway through, and at the end of radiation treatment, and analysed for changes associated with patient variables. The results demonstrate significant reductions in haematocrit, total white blood cell count, neutrophils, eosinophils, monocytes, lymphocytes and platelets occurred during definitive radiotherapy but remained within laboratory reference intervals. These data are important for anticipation of toxicity associated with combinations of radiotherapy and chemotherapy in dogs but do not support the routine monitoring of haematology parameters during definitive radiotherapy.


Primary subtype C HIV-1 infection in Harare, Zimbabwe.
Heterosexual transmission of HIV-1 is widespread in Southern Africa. Heteroduplex mobility assays (HMA) and phylogenetic analyses of V3-V5 envelope (env) gene sequences demonstrate that subtype C predominates in Zimbabwe. To elucidate factors contributing to the epidemic in Zimbabwe, clinical and virologic characteristics of recently acquired subtype C HIV-1 infection among 21 men and 1 woman were determined. In 12 of 19 men providing clinical histories, a sexually transmitted infection preceded serologic evidence of HIV-1, and 14 of 19 men complained of rash or fever before seroconversion. Quantitative p24 antigen levels, reverse transcriptase activity, and HIV RNA levels of 22 viral isolates correlated with in vitro infectivity in peripheral blood mononuclear cells (p < .05). Biologic phenotype assessed in MT-2 cells demonstrated that 3 of 22 isolates (14%) were syncytia inducing (SI) and the remaining 19 nonsyncytium inducing (NSI). Early growth of virus in culture was associated with increased plasma HIV RNA levels, decreased CD4 cell levels, and SI virus. Recent subtype C HIV-1 infection through heterosexual transmission in Zimbabwe demonstrated clinical and virologic features consistent with reports of seroconversion to subtype B viruses.


Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study.
Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19. We set-up a multicenter Italian collaboration to investigate the relationship between HCQ therapy and COVID-19 in-hospital mortality. In a retrospective observational study, 3,451 unselected patients hospitalized in 33 clinical centers in Italy, from February 19, 2020 to May 23, 2020, with laboratory-confirmed SARS-CoV-2 infection, were analyzed. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received HCQ with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores, with the addition of subgroup analyses. Out of 3,451 COVID-19 patients, 76.3% received HCQ. Death rates (per 1,000 person-days) for patients receiving or not HCQ were 8.9 and 15.7, respectively. After adjustment for propensity scores, we found 30% lower risk of death in patients receiving HCQ (HR=0.70; 95%CI: 0.59 to 0.84; E-value=1.67). Secondary analyses yielded similar results. The inverse association of HCQ with inpatient mortality was particularly evident in patients having elevated C-reactive protein at entry. HCQ use was associated with a 30% lower risk of death in COVID-19 hospitalized patients. Within the limits of an observational study and awaiting results from randomized controlled trials, these data do not discourage the use of HCQ in inpatients with COVID-19.


Usage of skin care products and risk of rheumatoid arthritis: results from the Swedish EIRA study.
The aim of this study was to investigate the association between exposure to cosmetics, often containing mineral oil, and the risk of developing rheumatoid arthritis (RA). The study was performed against the background that occupational exposure to mineral oil has recently been shown to be associated with an increased risk for RA in man, and that injection of or percutaneous exposure to mineral-oil-containing cosmetics can induce arthritis in certain rat strains. A population-based case-control study of incident cases of RA was performed among the population aged 18 to 70 years in a defined area of Sweden during May 1996 to December 2003. A case was defined as an individual from the study base, who received for the first time a diagnosis of RA according to the 1987 American College of Rheumatology criteria. Controls were randomly selected from the study base with consideration taken for age, gender and residential area. Cases (n = 1,419) and controls (n = 1,674) answered an extensive questionnaire regarding environmental and lifestyle factors including habits of cosmetic usage. The relative risk of developing RA was calculated for subjects with different cosmetic usage compared with subjects with low or no usage. Analysis was also performed stratifying the cases for presence/absence of rheumatoid factor and antibodies to citrulline-containing peptides. The relative risks of developing RA associated with use of cosmetics were all close to one, both for women and men, for different exposure categories, and in relation to different subgroups of RA. This study does not support the hypothesis that ordinary usage of common cosmetics as body lotions, skin creams, and ointments, often containing mineral oil, increase the risk for RA in the population in general. We cannot exclude, however, that these cosmetics can contribute to arthritis in individuals carrying certain genotypes or simultaneously being exposed to other arthritis-inducing environmental agents.


Six developmental trajectories characterize children with autism.
The goal of this study was to describe the typical longitudinal developmental trajectories of social and communication functioning in children with autism and to determine the correlates of these trajectories. Children with autism who were born in California from 1992 through 2001 and enrolled with the California Department of Developmental Services were identified. Subjects with <4 evaluations present in the database were excluded, resulting in a sample of 6975 children aged 2 to 14 years. Score sequences were constructed based on 9 evaluative items for social, communication, and repetitive behavior functioning. Typical trajectories were identified by using group-based latent trajectory modeling, and multinomial logistic regression models were used to determine the odds of classification within each trajectory varied by individual and family-level factors. Six typical patterns of social, communication, and repetitive behavior functioning were identified. These trajectories displayed significant heterogeneity in developmental pathways, and children whose symptoms were least severe at first diagnosis tended to improve more rapidly than those severely affected. One group of ∼10% of children experienced rapid gains, moving from severely affected to high functioning. Socioeconomic factors were correlated with trajectory outcomes; children with non-Hispanic, white, well-educated mothers were more likely to be high functioning, and minority children with less-educated mothers or intellectual disabilities were very unlikely to experience rapid gains. Children with autism have heterogeneous developmental pathways. One group of children evidenced remarkable developmental change over time. Understanding what drives these outcomes is thus critical.


Articulating Spacers as a Modified One-Stage Revision Total Knee Arthroplasty: A Preliminary Analysis.
Periprosthetic joint infection (PJI) following primary total knee arthroplasty (TKA) is a challenging complication for surgeons and patients alike. Although two-stage revision arthroplasty remains the gold standard PJI management in the United States, one-stage revision has had success in many parts of Europe. The aim of this study was to retrospectively review: 1) ultimate treatment success; 2) necessary antibiotic duration; 3) change in knee range of motion (ROM); and 4) final Knee Society Scores (KSS) in a case series of patients managed with retention of articulating antibiotic spacers following PJI. A retrospective review was performed on all patients treated for chronic PJI after primary TKA with retention of articulating antibiotic spacers at a minimum of one-year follow-up. Descriptive analysis was utilized to evaluate demographic characteristics, discharge destination, follow-up and antibiotic durations, Knee Society Score (KSS), and rates of treatment failure. Paired-Samples t-Tests were utilized to evaluate mean changes in flexion and extension between the preoperative and postoperative time periods. Our final cohort included 29 patients who were managed with articulating spacer retention at a mean follow-up of 16.8 (range, 12.0 to 23.1) months, with 21 patients (72.4%) medically unfit for multiple surgeons and eight patients (27.6%) satisfied with their function. Mean age was 61.3 (range, 41 to 85) years and mean Charlson Comorbidity Index (CCI) was 6.1 (mean, 0 to 12). The predominant infecting organism was Methicillin-Resistant Staphylococcus aureus (MRSA), which was involved in eight patients (27.6%). There was a significant increase in postoperative knee flexion (+14.7°; p<0.001) and no decrease in postoperative knee extension (+2.3°; p=0.361). Treatment success in our cohort was 79.3% (23 patients), with four patients (13.8%) having chronic wound drainage and two patients (6.9%) requiring multiple spacer exchanges. Sixteen patients (55.2%) were able to complete their antibiotic regimen, with the remaining patients unable to discontinue their antibiotics by latest clinic follow-up. One-stage exchange arthroplasty offers the advantage of a single procedure with analogous failure rates compared to two-stage exchange, decreases hospitalization, and improves cost-effectiveness, which is paramount in today's healthcare environment. To our knowledge, this is the first study in the United States to evaluate outcome scores, function, and success rate of a modified one-stage revision TKA technique. Although we are unable to make definitive conclusions based on the small sample size, the outcomes in this study are encouraging.


Divergence or disorder?: the politics of naming intersex.
The conditions once known under the umbrella terms intersex and hermaphroditism are now generally being called disorders of sex development in medical settings. The terms might seem synonymous, but in fact there are significant differences with controversial consequences. Hermaphroditism, an older term that can still be found in many medical writings, is vague, demeaning, and sensationalistic, conjuring mythic images of monsters and freaks. In the 1990s, activists advocated intersex to describe discordance between the multiple components of sex anatomy, but that word alienated many parents of affected children, as it suggests a self-conscious alternative gender identity and sexuality. Disorders of sex development also refers to intersex, but it deemphasizes the identity politics and sexual connotations associated with intersex, avoids the degradation associated with hermaphrodite, and instead highlights the underlying genetic or endocrine factors that cause prenatal sex development to take an unusual path. I argue that using disorder is problematic, because it implies medical conditions in need of repair, when some intersex anatomies, though atypical, do not necessarily need surgical or hormonal correction. I advocate a less pathologizing new term, divergence of sex development, that might reduce some of the conflict over nomenclature and satisfy intersex people, their parents, and their doctors.


Functional malignant cell heterogeneity in pancreatic neuroendocrine tumors revealed by targeting of PDGF-DD.
Intratumoral heterogeneity is an inherent feature of most human cancers and has profound implications for cancer therapy. As a result, there is an emergent need to explore previously unmapped mechanisms regulating distinct subpopulations of tumor cells and to understand their contribution to tumor progression and treatment response. Aberrant platelet-derived growth factor receptor beta (PDGFRβ) signaling in cancer has motivated the development of several antagonists currently in clinical use, including imatinib, sunitinib, and sorafenib. The discovery of a novel ligand for PDGFRβ, platelet-derived growth factor (PDGF)-DD, opened the possibility of a previously unidentified signaling pathway involved in tumor development. However, the precise function of PDGF-DD in tumor growth and invasion remains elusive. Here, making use of a newly generated Pdgfd knockout mouse, we reveal a functionally important malignant cell heterogeneity modulated by PDGF-DD signaling in pancreatic neuroendocrine tumors (PanNET). Our analyses demonstrate that tumor growth was delayed in the absence of signaling by PDGF-DD. Surprisingly, ablation of PDGF-DD did not affect the vasculature or stroma of PanNET; instead, we found that PDGF-DD stimulated bulk tumor cell proliferation by induction of paracrine mitogenic signaling between heterogeneous malignant cell clones, some of which expressed PDGFRβ. The presence of a subclonal population of tumor cells characterized by PDGFRβ expression was further validated in a cohort of human PanNET. In conclusion, we demonstrate a previously unrecognized heterogeneity in PanNET characterized by signaling through the PDGF-DD/PDGFRβ axis.


Microplastics in the sediments of a UK urban lake.
While studies on microplastics in the marine environment show their wide-distribution, persistence and contamination of biota, the freshwater environment remains comparatively neglected. Where studies on freshwaters have been undertaken these have been on riverine systems or very large lakes. We present data on the distribution of microplastic particles in the sediments of Edgbaston Pool, a shallow eutrophic lake in central Birmingham, UK. These data provide, to our knowledge, the first assessment of microplastic concentrations in the sediments of either a small or an urban lake and the first for any lake in the UK. Maximum concentrations reached 25-30 particles per 100 g dried sediment (equivalent to low hundreds kg-1) and hence are comparable with reported river sediment studies. Fibres and films were the most common types of microplastic observed. Spatial distributions appear to be due to similar factors to other lake studies (i.e. location of inflow; prevailing wind directions; propensity for biofouling; distribution of macroplastic debris) and add to the growing burden of evidence for microplastic ubiquity in all environments.


Physician Associate and General Practitioner Consultations: A Comparative Observational Video Study.
Physician associates, known internationally as physician assistants, are a mid-level practitioner, well established in the United States of America but new to the United Kingdom. A small number work in primary care under the supervision of general practitioners, where they most commonly see patients requesting same day appointments for new problems. As an adjunct to larger study, we investigated the quality of the patient consultation of physician associates in comparison to that of general practitioners. We conducted a comparative observational study using video recordings of consultations by volunteer physician associates and general practitioners with consenting patients in single surgery sessions. Recordings were assessed by experienced general practitioners, blinded to the type of the consulting practitioner, using the Leicester Assessment Package. Assessors were asked to comment on the safety of the recorded consultations and to attempt to identify the type of practitioner. Ratings were compared across practitioner type, alongside the number of presenting complaints discussed in each consultation and the number of these which were acute, minor, or regarding a chronic condition. We assessed 62 consultations (41 general practitioner and 21 physician associates) from five general practitioners and four physician associates. All consultations were assessed as safe; but general practitioners were rated higher than PAs in all elements of consultation. The general practitioners were more likely than physician associates to see people with multiple presenting complaints (p<0.0001) and with chronic disease related complaints (p = 0.008). Assessors correctly identified general practitioner consultations but not physician associates. The Leicester Assessment Package had limited inter-rater and intra-rater reliability. The physician associate consultations were with a less complex patient group. They were judged as competent and safe, although general practitioner consultations, unsurprisingly, were rated as more competent. Physician associates offer a complementary addition to the medical workforce in general practice.


A new Poisson Liu Regression Estimator: method and application.
This paper considers the estimation of parameters for the Poisson regression model in the presence of high, but imperfect multicollinearity. To mitigate this problem, we suggest using the Poisson Liu Regression Estimator (PLRE) and propose some new approaches to estimate this shrinkage parameter. The small sample statistical properties of these estimators are systematically scrutinized using Monte Carlo simulations. To evaluate the performance of these estimators, we assess the Mean Square Errors (MSE) and the Mean Absolute Percentage Errors (MAPE). The simulation results clearly illustrate the benefit of the methods of estimating these types of shrinkage parameters in finite samples. Finally, we illustrate the empirical relevance of our newly proposed methods using an empirically relevant application. Thus, in summary, via simulations of empirically relevant parameter values, and by a standard empirical application, it is clearly demonstrated that our technique exhibits more precise estimators, compared to traditional techniques - at least when multicollinearity exist among the regressors.


Ending the epidemic: Critical role of primary HIV infection.
Early identification and immediate treatment of individuals newly infected with HIV is important for two reasons: it benefits the long-term health of the infected patient, and it reduces onward HIV transmission. Primary HIV infection (PHI) reflects the period following HIV acquisition during which viraemia bursts until the establishment of a stable plasma HIV-RNA level approximately six months post infection. During this period, patients are particularly contagious and are often unaware of the infection. As a consequence, PHI disproportionally affects onward transmission. During PHI the immune system is irreparably damaged and persistent viral reservoirs are formed. Initiating antiretroviral therapy (ART) during PHI could potentially lead to a functional cure through early and prolonged viral suppression. Unfortunately, symptoms of PHI are nonspecific and the diagnosis is frequently missed. This impedes timely diagnosis and prompt initiation of ART. To increase awareness and underscore the importance of immediate ART initiation, we describe here the pathogenesis, clinical presentation, and impact of treating PHI.


Atherosclerosis. Potential targets for stabilization and regression.
Reviewed are various aspects of atherosclerotic plaque stabilization and regression in humans and experimental animals. Plaque regression is a function of the dynamic balance among initiation, progression, stabilization, and removal of plaque constituents. Pseudoregression, the result of the triad thrombolysis, age- or lesion-dependent arterial dilatation, and relaxation of vasospasm, may readily give rise to angiographic misinterpretation. Although lowering of plasma cholesterol and low density lipoprotein-cholesterol has demonstrated significant clinical benefits in a number of clinical trials, the magnitude of angiographic regressive changes is relatively small despite aggressive lipid-lowering regimens. The emerging need for alternative or complementary therapeutic interventions has been emphasized. In particular, they should be targeted to pivotal cellular or molecular mechanisms in initiation, progression, or stabilization. Potentially important therapeutic targets include the use of antioxidants or free radical scavengers such as Probucol or its analogues, butylated hydroxytoluene, tocopherols, and possibly the tocotrienols. Other therapeutic targets include intimal monocyte-macrophage recruitment, macrophage cholesterol acyltransferase inhibition, stimulation of the high density lipoprotein-mediated reverse cholesterol transport system, smooth muscle cell migration to and proliferation in the arterial intima, and intimal connective tissue synthesis. Whether the isoprenylated proteins associated with the cholesterol biosynthetic pathway will give rise to compounds regulating smooth muscle cell growth has yet to be determined. Because of the importance of thrombosis in the pathogenesis and progression of lesions, the need to develop interventional strategies targeted at endothelial cell thromboresistance and thromboregulation must assume a high priority in future research and development. Other areas of therapeutic promise include the calcium channel blockers and angiotensin converting enzyme inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)


The influence of intrapersonal sensorimotor experiences on the corticospinal responses during action-observation.
The coupling of perception and action has been strongly indicated by evidence that the observation of an action primes a response in the observer. It has been proposed that these primed responses may be inhibited when the observer is able to more closely distinguish between self- and other-generated actions - the greater the distinction, then the greater the inhibition of the primed response. This self-other distinction is shown to be enhanced following a period of visual feedback of self-generated action. The present study was designed to examine how sensorimotor experiences pertaining to self-generated action affect primed responses from observed actions. Single-pulse transcranial magnetic stimulation was used to investigate corticospinal activity elicited during the observation of index- and little-finger actions before and after training (self-generated action). For sensorimotor training, participants executed finger movements with or without visual feedback of their own movement. Results showed that the increases in muscle-specific corticospinal activity elicited from action-observation persisted after training without visual feedback, but did not emerge following training with visual feedback. This inhibition in corticospinal activity during action-observation following training with vision could have resulted from the refining of internal models of self-generated action, which then led to a greater distinction between "self" and "other" actions.


Nitric oxide synthase inhibition reduces leg glucose uptake but not blood flow during dynamic exercise in humans.
Nitric oxide (NO) appears to play a role in contraction-stimulated glucose uptake in isolated rodent skeletal muscle; however, no studies have examined this question in humans. Seven healthy men completed two 30-min bouts of supine cycling exercise at 60 +/- 2% peak pulmonary oxygen uptake (VO2 peak), separated by 90 min of rest. The NO synthase inhibitor N(G)-monomethyl-L-arginine ([L-NMMA]; total dose 5 mg/kg body weight) or saline (control) were administered via the femoral artery for the final 20 min of exercise in a randomized blinded crossover design. L-Arginine (5 mg/kg body weight) was co-infused during the final 5 min of each exercise bout. Leg blood flow (LBF) was measured by thermodilution in the femoral vein, and leg glucose uptake was calculated as the product of LBF and femoral arteriovenous (AV) glucose difference. L-NMMA infusion significantly (P < 0.05) reduced leg glucose uptake compared with control (48 +/- 12% lower at 15 min, mean +/- SE). The reduction in glucose uptake was due solely to a decrease in AV glucose difference, as there was no effect of L-NMMA infusion on LBF during exercise. Co-infusion of L-arginine restored glucose uptake during L-NMMA infusion to levels similar to control. These results indicate that NO production contributes substantially to exercise-mediated skeletal muscle glucose uptake in humans independent of skeletal muscle blood flow.


Recruiting patients to clinical trials: lessons from studies of growth hormone treatment in renal failure.
Issues raised by the recruitment of children to trials of growth hormone treatment for short stature in chronic renal failure are reported. Information needs of parents and children are discussed, the latter should take account of the children's developmental level and anticipated involvement in decision making. When the incidence of certain side effects is low and probably unquantifiable there are particular problems; failure to include these in information sheets may compromise informed consent but inclusion will, at least for some families, make an already difficult decision even more complicated. A process of recruitment is described which attempts to protect against bias and which balances the requirement to impart neutral information with appropriate clinical involvement in the decision to enter the study. Other functions of the recruitment process are identified. Analysis of understanding and decision making demonstrates that good understanding is neither necessary nor sufficient for ease of decision making. The recruitment process was time consuming and needs planning and funding in future studies. Many of these issues are of general importance for trials of treatment in children.


Activation of the p70 S6 kinase by all-trans-retinoic acid in acute promyelocytic leukemia cells.
Although the mechanisms by which all-trans-retinoic acid (RA) regulates gene transcription are well understood, very little is known on the signaling events regulating RA-dependent initiation of mRNA translation. We examined whether the mammalian target of rapamycin (mTOR)/p70 S6 kinase pathway is activated by RA. RA treatment of sensitive cell lines resulted in phosphorylation/activation of mTOR and downstream induction of p70 S6 kinase activity. Such phosphorylation/activation of p70 S6 kinase was inducible in primary acute promyelocytic leukemia (APL) blasts and RA-sensitive NB-4 cells, but was defective in an NB-4 variant cell line (NB-4.007/6) that is resistant to the biologic effects of RA. The RA-dependent activation of p70 S6 kinase was also phosphatidylinositol 3' kinase (PI3'K)-dependent, and resulted in downstream phosphorylation of the S6 ribosomal protein on Ser235/236 and Ser240/244, events important for initiation of translation for mRNAs with oligopyrimidine tracts in their 5' untranslated region. RA treatment of leukemia cells also resulted in an mTOR-mediated phosphorylation of the 4E-BP1 repressor of mRNA translation, to induce its deactivation and dissociation from the eukaryotic initiation factor-4E (eIF-4E) complex. Altogether, these findings provide evidence for the existence of a novel RA-activated cellular pathway that regulates cap-dependent translation, and strongly suggest that this cascade plays a role in the induction of retinoid responses in APL cells.


Species as a Heuristic: Reconciling Theory and Practice.
Species are crucial to most branches of biological research, yet remain controversial in terms of definition, delimitation, and reality. The difficulty of resolving the "species problem" stems from the tension between their theoretical concept as groups of evolving and highly variable organisms and the practical need for a stable and comparable unit of biology. Here, we suggest that treating species as a heuristic can be consistent with a theoretical definition of what species are and with the practical means by which they are identified and delimited. Specifically, we suggest that theoretically species are heuristic since they comprise clusters of closely related individuals responding in a similar manner to comparable sets of evolutionary and ecological forces, whilst they are practically heuristic because they are identifiable by the congruence of contingent properties indicative of those forces. This reconciliation of the theoretical basis of species with their practical applications in biological research allows for a loose but relatively consistent definition of species based on the strategic analysis and integration of genotypic, phenotypic, and ecotypic data. [Cohesion; heuristic; homeostasis; lineage; species problem.].


Novel genome and genome-wide SNPs reveal early fragmentation effects in an edge-tolerant songbird population across an urbanized tropical metropolis.
Although edge-tolerant species are known to benefit from habitat fragmentation, less is known about the population genetic impacts fragmentation may exert on edge-tolerant species. We examined the landscape genomic structure of an edge-tolerant forest-dependent bird species, the Striped Tit-Babbler Mixornis gularis, in the heavily urbanized island of Singapore to determine if two centuries of fragmentation have led to signs of isolation and loss of population-genetic diversity in different parts of the island. We obtained a high-quality complete reference genome with 78x coverage. Using almost 4000 SNPs from double-digest RAD-Sequencing across 46 individuals, we found that the population has likely experienced a recent contraction in effective population size and presently exhibits low population genetic diversity. Using empirical and simulation-based landscape genomic analyses, we also found that the subtle population genetic structure observed in the Striped Tit-Babbler population in Singapore is likely driven by isolation by distance resulting from limited dispersal. Our results demonstrate that population genetic impoverishment and subdivision can accumulate at relatively rapid rates in edge-tolerant bird species such as the Striped Tit-Babbler as a result of fragmentation, and that subtle spatial genetic structure can be detected over fine spatial and temporal scales using relatively few multilocus genomic SNPs.


Effect of cigarette prices on smoking initiation and cessation in China: a duration analysis.
China is the world's largest producer and consumer of cigarettes. The status of tobacco as both a contributor to China's economy and a liability for the health of its population may complicate the use of taxes for addressing smoking in the country. Understanding how cigarette prices affect transitions in smoking behaviour in China can increase understanding of how China's high smoking rates can be influenced by tax policy. In order to estimate the effect of cigarette prices on smoking initiation and cessation in China, we construct pseudo-longitudinal samples for duration analysis using data from the Global Adult Tobacco Survey China 2010. We use the historical variation in prices representative of 4 China regions over a 20-year period to identify the average price effect on the hazards of initiation and cessation while controlling for unobserved fixed and time-varying region characteristics. We find that initiation rates fall in response to higher prices (with a price elasticity of initiation estimated at -0.95 for men and -1.07 overall). The effect of prices on smoking in China is likely to occur through averting initiation over time. At the population level, cessation behaviour may be less responsive to price increases as the wide range of cigarette prices in China may provide relatively high opportunity for switching to lower priced brands.


The dysbindin gene (DTNBP1) is associated with methamphetamine psychosis.
The dysbindin (DTNBP1 [dystrobrevin-binding protein 1]) gene has repeatedly been shown to be associated with schizophrenia across diverse populations. One study also showed that risk haplotypes were shared with a bipolar disorder subgroup with psychotic episodes, but not with all cases. DTNBP1 may confer susceptibility to psychotic symptoms in various psychiatric disorders besides schizophrenia. Methamphetamine psychosis, the psychotic symptoms of which are close to those observed in schizophrenia, was investigated through a case (n = 197)-control (n = 243) association analyses of DTNBP1. DTNBP1 showed significant associations with methamphetamine psychosis at polymorphisms of P1635 (rs3213207, p = .00003) and SNPA (rs2619538, p = .049) and the three-locus haplotype of P1655 (rs2619539)-P1635-SNPA (permutation p = .0005). The C-A-A haplotype, which was identical to the protective haplotype previously reported for schizophrenia and psychotic bipolar disorders, was a protective factor (p = .0013, odds ratio [OR] = .62, 95% confidence interval [CI] .51-.77) for methamphetamine psychosis. The C-G-T haplotype was a risk for methamphetamine psychosis (p = .0012, OR = 14.9, 95% CI 3.5-64.2). Our genetic evidence suggests that DTNBP1 is involved in psychotic liability not only for schizophrenia but also for other psychotic disorders, including substance-induced psychosis.


Effect of pulmonary surfactant on the dissolution, stability and uptake of zinc oxide nanowires by human respiratory epithelial cells.
Inhaled nanoparticles (NPs) have high-deposition rates in the alveolar region of the lung but the effects of pulmonary surfactant (PS) on nanoparticle bioreactivity are unclear. Here, the impact of PS on the stability and dissolution of ZnO nanowires (ZnONWs) was investigated, and linked with their bioreactivity in vitro with human alveolar epithelial type 1-like cells (TT1). Pre-incubation of ZnONWs with Curosurf® (a natural porcine PS) decreased their dissolution at acidic pH, through the formation of a phospholipid corona. Confocal live cell microscopy confirmed that Curosurf® lowered intracellular dissolution, thus delaying the onset of cell death compared to bare ZnONWs. Despite reducing dissolution, Curosurf® significantly increased the uptake of ZnONWs within TT1 cells, ultimately increasing their toxicity after 24 h. Although serum improved ZnONW dispersion in suspension similar to Curosurf®, it had no effect on ZnONW internalization and toxicity, indicating a unique role of PS in promoting particle uptake. In the absence of PS, ZnONW length had no effect on dissolution kinetics or degree of cellular toxicity, indicating a less important role of length in determining ZnONW bioreactivity. This work provides unique findings on the effects of PS on the stability and toxicity of ZnONWs, which could be important in the study of pulmonary toxicity and epithelial-endothelial translocation of nanoparticles in general.


Length of Stay at Inpatient Rehabilitation Facility and Stroke Patient Outcomes.
To examine the association of inpatient rehabilitation facility (IRF) length of stay (LOS) with stroke patient outcomes. A secondary data analysis of the Uniform Data System for Medical Rehabilitation database. Stroke patients discharged from IRFs in the United States between 2009 and 2011 were identified and divided into mild (n = 639), moderate (n = 2,065), and severely (n = 2,077) impaired groups. Study outcomes included cognition and motor functional gains measured by the Functional Independence Measure (FIM) instrument and discharge to the community. The average LOS was 8.9, 13.9, and 22.2 days for mild, moderate, and severely impaired stroke patients, respectively. After controlling for FIM admission and other important covariates, a longer LOS was associated with a modest increase in cognition gain (β = 0.038, p = .0045) for the moderately impaired patients, and a modest increase in cognition (β = 0.13, p < .0001) and motor gains (β = 0.25, p < .0001) as well as a tendency for discharge to the community (OR = 1.01, 95% CI = 1.00-1.02) among the severely impaired patients. However, a longer LOS showed a negative association with functional gains among the mildly impaired patients as well as discharge to community for both mild and moderately impaired patients. The association of IRF LOS and patient outcomes varied by stroke impairment severity, positively for more severely impaired patients and negatively for mildly impaired patients. The study provides evidence for the care of stroke patients at the IRF setting.


HIV prevention while the bulldozers roll: exploring the effect of the demolition of Goa's red-light area.
Interventions targeting sex-workers are pivotal to HIV prevention in India. Community mobilisation is considered by the National AIDS Control Programme to be an integral component of this strategy. Nevertheless societal factors, and specifically policy and legislation around sex-work, are potential barriers to widespread collectivisation and empowerment of sex-workers. Between November 2003 and December 2005 we conducted participatory observation and rapid ethnographic mapping with several hundred brief informant interviews, in addition to 34 semi-structured interviews with key-informants, 16 in-depth interviews with female sex-workers, and 3 focus-group-discussions with clients and mediators. This provides a detailed examination of the demolition of Baina, one of India's large red-light areas, in 2004, and one of the first accounts of the effect of dismantling the red-light area on the organisation of sex-work and sex-workers' sexual risk. The results suggest that the concentrated and homogeneous brothel-based sex-work environment rapidly evolved into heterogeneous, clandestine and dispersed modes of operation. The social context of sex-work that emerged from the dust of the demolition was higher risk and less conducive to HIV prevention. The demolition acted as a negative structural intervention; a catastrophic event that fragmented sex-workers' collective identity and agency and rendered them voiceless and marginalised. The findings suggest that an abolitionist approach to sex-work and legislation or policy that either criminalises this large group of women, or renders them as invisible victims, will increase the stigma and exclusion they experience. For the targeted HIV prevention approaches advocated by the National AIDS Control Programme to be effective, there is a need for legislation and policy that supports sex-workers' agency and self-organisation and enables them to create a safer working environment for themselves.


Distortion-free spectrum sliced microwave photonic signal processor: analysis, design and implementation.
A new switchable microwave photonic filter based on a novel spectrum slicing technique is presented. The processor enables programmable multi-tap generation with general transfer function characteristics and offers tunability, reconfigurabiliy, and switchability. It is based on connecting a dispersion controlled spectrum slicing filter after the modulated bipolar broadband light source, which consequently generates multiple spectrum slices with bipolarity, and compensates dispersion induced RF degradation simultaneously within a single device. A detailed theoretical model for this microwave photonic filter design is presented. Experimental results are presented which verify the model, and demonstrate a 33 bipolar-tap microwave filter with significant reduction of passband attenuations at high frequencies. The RF response improvement of the new microwave photonic filter is investigated, for both an ideal linear group delay line and for the experimental fiber delay line that has second order group delay and the results show that this new structure is effective for RF filters with various free spectral range values and spectrum slice bandwidths. Finally, a switchable bipolar filter that has a square-top bandpass filter response with more than 30 dB stopband attenuation that can be switched on/off via software control is demonstrated.


Occupational role history: a screening tool for psychiatric occupational therapy.
Psychiatric hospitalization has become telescoped, thus focusing on short-term acute care. Since discharge plans are needed on admission, occupational therapists must evaluate the patient quickly and succinctly. A screening tool was developed as a preliminary device to identify critical information in two major areas: patterns of skills and achievement or patterns of dysfunction in past and current occupational role; and the degree of balance or imbalance between leisure activities and those activities associated with occupational role. The screening tool, the Occupational Role History, was used in a pilot study on 20 adult inpatients at the UCLA Neuropsychiatric Institute. The results of the pilot study suggest that this tool is useful in establishing treatment priorities from an occupational therapy perspective.


In-depth proteome mining of cultured Catharanthus roseus cells identifies candidate proteins involved in the synthesis and transport of secondary metabolites.
Madagascar periwinkle (Catharanthus roseus) is the major source of terpenoid indole alkaloids, such as vinblastine or vincristine, used as natural drugs against various cancers. In this study, we have extensively analyzed the proteome of cultured C. roseus cells. Comparison of the proteomes of two independent cell lines with different terpenoid indole alkaloid metabolism by 2D-DIGE revealed 358 proteins that differed quantitatively by at least a twofold average ratio. Of these, 172 were identified by MS; most corresponded to housekeeping proteins. Less abundant proteins were identified by LC separation of tryptic peptides of proteins from one of the lines. We identified 1663 proteins, most of which are housekeeping proteins or involved in primary metabolism. However, 63 enzymes potentially involved in secondary metabolism were also identified, of which 22 are involved in terpenoid indole alkaloid biosynthesis and 16 are predicted transporters putatively involved in secondary metabolite transport. About 30% of the proteins identified have an unclear or unknown function, indicating important gaps in knowledge of plant metabolism. This study is an important step toward elucidating the proteome of C. roseus, which is critical for a better understanding of how this plant synthesizes terpenoid indole alkaloids.