Aggression and the psychological self.
In this paper we explore the idea of aggression as a defence against threats to the psychological self. This aspect of the self allows reflection about people in psychological terms and develops, in the first three years of life, through appreciation of mental states in the other. When the object is unpredictable or hostile, recognition of this is painful to the child, and his reflective function will not be adequately established. The defences of aggression or avoidance will be invoked very frequently. In time, aggression may become an organising influence in the construction of the self; pathological destructiveness then takes the place of emotional relatedness and concern for the other. Psychoanalytic treatment no longer works primarily by addressing conflict. Instead, particularly through interpretations of transference and countertransference, the analyst recreates an intersubjective process which enhances the patient's reflective self, this time in the safety of a benign relationship.


Extensive error in the number of genes inferred from draft genome assemblies.
Current sequencing methods produce large amounts of data, but genome assemblies based on these data are often woefully incomplete. These incomplete and error-filled assemblies result in many annotation errors, especially in the number of genes present in a genome. In this paper we investigate the magnitude of the problem, both in terms of total gene number and the number of copies of genes in specific families. To do this, we compare multiple draft assemblies against higher-quality versions of the same genomes, using several new assemblies of the chicken genome based on both traditional and next-generation sequencing technologies, as well as published draft assemblies of chimpanzee. We find that upwards of 40% of all gene families are inferred to have the wrong number of genes in draft assemblies, and that these incorrect assemblies both add and subtract genes. Using simulated genome assemblies of Drosophila melanogaster, we find that the major cause of increased gene numbers in draft genomes is the fragmentation of genes onto multiple individual contigs. Finally, we demonstrate the usefulness of RNA-Seq in improving the gene annotation of draft assemblies, largely by connecting genes that have been fragmented in the assembly process.


Microcomputed tomographic and histologic analysis of anorganic bone matrix coupled with cell-binding peptide suspended in sodium hyaluronate carrier after sinus augmentation: a clinical study.
Anorganic bovine hydroxyapatite matrix (ABM), when coupled with synthetic cell-binding peptide (P15), mimics the cell-binding region of type 1 collagen and is commercially available suspended in a sodium hyaluronate carrier. The aim of the present study, therefore, was to test the efficacy of ABM/P-15 Putty (DENTSPLY Friadent CeraMed) as a sole graft material for sinus augmentation in patients with severely resorbed posterior maxillae. Sinus augmentation was performed in 10 patients using ABM/P-15 Putty and two provisional dental implants (3.0 mm in diameter). The graft and implants were placed simultaneously with the aid of a surgical stent. After 8 or 16 weeks, the implants were removed using a 4.25-mm trephine bur; this was followed by immediate placement of wider-diameter (5.5-mm) implants. All 20 implants were scanned by microcomputed tomography to determine bone mineral density (BMD), percent bone volume (PBV), and percent bone contact (PBC). There was a significant increase in the BMD of bone around the implants at 8 weeks and 16 weeks compared to native residual (control) bone. There was no significant difference in PBV or PBC between 8 weeks and 16 weeks. The average increase in bone height at 16 weeks was 9.63 ± 1 mm. Microcomputed tomographic images and histologic sections showed dense graft particles surrounded by vital trabecular bone. BMD increases as early as 8 weeks and does not show an additional increase after 16 weeks. PepGen P-15 Putty was found to be a promising osteoconductive graft for sinus augmentation, supporting immediate placement of implants.


Genome-wide analysis of host responses to the Pseudomonas aeruginosa type III secretion system yields synergistic effects.
The type III secretion system (TTSS) is a dedicated bacterial pathogen protein targeting system that directly affects host cell signalling and response pathways. Our goal was to identify host responses to the Pseudomonas aeruginosa effectors, introduced into target cells utilizing the TTSS. We carried out expression profiling of a human lung pneumocyte cell line A549 exposed to isogenic mutants of P. aeruginosa PAK lacking individual or a combination of TTSS components. We then devised a data analysis method to isolate the key responses to specific secreted bacterial effector proteins as well as components of the TTSS machinery. Individually, the effector proteins elicited host responses consistent with their known functions, many of which were cell cycle-related. However, our analysis has shown that the effector proteins elicit a distinct host transcriptional response when present in combination, suggesting a synergistic effect. Furthermore, the pattern of host transcriptional responses is consistent with the pore forming ability of the TTSS needle complex. This study shows that the individual components of the TTSS define an integrated system and that a systems biology approach is required to fully understand the complex interplay between pathogen and host.


Ruthenium/Graphene-like Layered Carbon Composite as an Efficient Hydrogen Evolution Reaction Electrocatalyst.
Efficient water splitting through electrocatalysis has been studied extensively in modern energy devices, while the development of catalysts with activity and stability comparable to those of Pt is still a great challenge. In this work, we successfully developed a facile route to synthesize graphene-like layered carbon (GLC) from a layered silicate template. The obtained GLC has layered structure similar to that of the template and can be used as support to load ultrasmall Ru nanoparticles on it in supercritical water. The specific structure and surface properties of GLC enable Ru nanoparticles to disperse highly uniformly on it even at a large loading amount (62 wt %). When the novel Ru/GLC was used as catalyst on a glass carbon electrode for hydrogen evolution reaction (HER) in a 0.5 M H2SO4 solution, it exhibits an extremely low onset potential of only 3 mV and a small Tafel slope of 46 mV/decade. The outstanding performance proved that Ru/GLC is highly active catalyst for HER, comparable with transition-metal dichalcogenides or selenides. As the price of ruthenium is much lower than platinum, our study shows that Ru/GLC might be a promising candidate as an HER catalyst in future energy applications.


Patient use of smartphones to communicate subjective data in clinical trials.
Various methods have been used in clinical trials to collect time-sensitive subjective responses, including study diaries, telephone interviews, and use of text messaging. However, all of these methods are limited by the uncertainty of when the participants enrolled in the study actually record their responses. This technical note reports on the utility of the BlackBerry smartphone to collect such data and why such a system provides advantages over other methods to report subjective ratings in clinical studies. The Centre for Contact Lens Research developed an on-line web-enabled system that permits participants to record and immediately transmit subjective rating scores in numerical form directly into a web-enabled database. This, combined with the utility of BlackBerrys, enabled time-specific e-mail requests to be sent to the study participants and then for that data to be simultaneously transmitted to the web-enabled database. This system has been used in several clinical trials conducted at the Centre for Contact Lens Research, in which data were collected at various times and in several specific locations or environments. In the clinical trials conducted using this system, participants provided responses on 97.5% of occasions to the requests for data generated by the automated system. When the request was for data on a set date, this method resulted in responses of 84.1% of the time. The series of clinical trials reported here show the benefits of the utilization of the BlackBerry to collect time- or environment-sensitive data via a web-enabled system.


Differentiating impairment levels in temporal versus spatial aspects of linguopalatal contacts in Friedreich's ataxia.
Electropalatography (EPG) was used to describe the pattern of linguopalatal contact and the consonant phase durations exhibited by a group of seven individuals with dysarthria associated with Friedreich's ataxia (FRDA). A group of 14 non-neurologically impaired individuals served as controls. The Reading Electropalatograph (EPG3) system was used to record linguopalatal contact during production of the target consonants (/t/, /l/, /s/, /k/) elicited in five words of CV and CVC construction, with the target consonants in word initial position. These words were embedded into short sentences and repeated five times by each participant. The FRDA group exhibited significantly increased consonant durations compared with the controls while maintaining normal linguopalatal contact patterns. These findings suggest that the articulatory impairment in FRDA manifests as a temporal rather than spatial disturbance.


The determination of the levels of burnout syndrome, organizational commitment, and job satisfaction of the health workers.
The concept of burnout is an important element for efficiency in occupational groups such as health and education, which necessitate constant communication with people and have a busy schedule. The determination of the levels of burnout syndrome, organizational commitment, and job satisfaction of the health workers. A questionnaire consisting of four parts was prepared so as to measure the levels of organizational commitment, job satisfaction, and burnout of the medical staff of the institution. The data for this research were gained by a questionnaire sent to 370 medical staff (doctors, nurses, contract staff, and other employees). Kolmogorov Smirnov test, t-test, ANOVA, Tukey multiple comparison test and Pearson's correlation analysis were used to this study. The average age of the employees taking part in the questionnaire was calculated as 34.30 years (min: 18 years, max: 59 years). The proportional value of the individuals with their 0-5 years working period in the institution was observed as 58.1%. An individual's interior work satisfaction, education level, hours worked at the hospital and their titles are also statistically important (P< 0.05). There is a positive correlation and significant relation between medical staffs' emotional exhaustion and desensitization (r = 0.573). There is a positive correlation and significant relation between normative commitment sub dimension, interior and exterior job satisfaction (r = 0.449, r = 0.472). Efforts to reduce the job burnout and psychological support for health care workers support motivation in order to provide better services to increase significantly. Thus, both personal productivity will be increased, and gain will be obtained in the institutional sense.


Adult height and head and neck cancer: a pooled analysis within the INHANCE Consortium.
Several epidemiological studies have shown a positive association between adult height and cancer incidence. The only study conducted among women on mouth and pharynx cancer risk, however, reported an inverse association. This study aims to investigate the association between height and the risk of head and neck cancer (HNC) within a large international consortium of HNC. We analyzed pooled individual-level data from 24 case-control studies participating in the International Head and Neck Cancer Epidemiology Consortium. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated separately for men and women for associations between height and HNC risk. Educational level, tobacco smoking, and alcohol consumption were included in all regression models. Stratified analyses by HNC subsites were performed. This project included 17,666 cases and 28,198 controls. We found an inverse association between height and HNC (adjusted OR per 10 cm height = 0.91, 95% CI 0.86-0.95 for men; adjusted OR = 0.86, 95% CI 0.79-0.93 for women). In men, the estimated OR did vary by educational level, smoking status, geographic area, and control source. No differences by subsites were detected. Adult height is inversely associated with HNC risk. As height can be considered a marker of childhood illness and low energy intake, the inverse association is consistent with prior studies showing that HNC occur more frequently among deprived individuals. Further studies designed to elucidate the mechanism of such association would be warranted.


Antipsychotics associated with pulmonary embolism in a Swedish medicolegal autopsy series.
To determine the association between fatal pulmonary embolism and use of antipsychotic drugs in a Swedish medicolegal autopsy series. Persons aged 18-65 years and subjected to a medicolegal autopsy in 1992-2005 were selected. On the basis of external cause of death, determined by the forensic pathologist, unnatural deaths (including fatal intoxications) were excluded and participants in whom pulmonary embolism was the cause of death were identified. Use of antipsychotics was based on the results of the postmortem analyses and categorized as use of high-potency first-generation antipsychotics, low-potency first-generation antipsychotics, second-generation antipsychotics or no use of antipsychotics. Logistic regression analyses were performed. Use of antipsychotics was verified in 538 of the 14,439 included participants. Pulmonary embolism was recorded as the cause of death in 279 participants and 33 of these used antipsychotics. Use of low-potency first-generation antipsychotics and second-generation antipsychotics was significantly associated with fatal pulmonary embolism (adjusted odds ratio: 2.39; 95% confidence interval: 1.46-3.92 and 6.91; 95% confidence interval: 3.95-12.10, respectively). Out of 26 participants classified as high-potency first-generation antipsychotic drug users, none had pulmonary embolism as the cause of death. Pulmonary embolism was overrepresented among medicolegal autopsy cases identified as users of low-potency first-generation and second-generation antipsychotics.


Measuring the coverage of nutrition interventions along the continuum of care: time to act at scale.
The global community is committed to addressing malnutrition. And yet, coverage data for high-impact interventions along the continuum of care remain scarce due to several measurement and data collection challenges. In this analysis paper, we identify 24 nutrition interventions that should be tracked by all countries, and determine if their coverage is currently measured by major household nutrition and health surveys. We then present three case studies, using published literature and empirical data from large-scale initiatives, to illustrate the kind of data collection innovations that are feasible. We find that data are not routinely collected in a standardised way across countries for most of the core set of interventions. Case studies-of growth monitoring and screening for acute malnutrition, infant and young child feeding counselling, and nutrition monitoring in India-highlight both challenges and potential solutions. Advancing the nutrition intervention coverage measurement agenda is essential for sustained progress in driving down rates of malnutrition. It will require (1) global consensus on a core set of validated coverage indicators on proven, high-impact nutrition-specific interventions; (2) the inclusion of coverage measurement and indicator guidance in WHO intervention recommendations; (3) the incorporation of these indicators into data collection mechanisms and relevant intervention delivery platforms; and (4) an agenda for continuous measurement improvement.


A formative study of disposal and re-use of old mosquito nets by communities in Malindi, Kenya.
About 30 million insecticide treated mosquito nets have been distributed in Kenya since 2001 and ownership is approaching full coverage. As a consequence of this achievement, Kenya is faced with the challenge of disposing old mosquito nets that are no longer in use. The study aimed at investigating ways of disposal and re-use of old and torn nets by end users. A formative study was conducted in the former Malindi District, which is comprised of Malindi and Magarini sub-counties of Kilifi County in Coastal Kenya. A total of 6 Focus Group Discussions, 10 Key Informant Interviews and 9 transect walks/drives were undertaken. Data from the different sources were analysed separately and triangulated for similarities and differences. There were variations in disposal and re-use of old nets between urban and rural or peri-urban residents. In all settings, people adopted innovative and beneficial ways of re-using old, expired nets, and those that were damaged beyond repair. Common causes of damage were fire, children, domestic animals sharing the sleeping room and friction from the bed poles while hanging or tacking it in under a sleeping mat. Re-use was most prominent in farming activities (78%) and less to for use in mosquito control, like window screening (15%). The remaining 8% was related to making ropes, swings, footballs, goal posts and fishing nets. Advantageous texture and nature of the netting material, perceived economic benefit and lack of guidelines for disposal were the main reasons cited by residents for re-using old nets. It is important that re-use and disposal of old mosquito nets is distinguished from misuse of newly distributed mosquito nets. Alternative uses of old nets as opposed to misuse of new nets was found to be common in our study.


Recruitment to publicly funded trials--are surgical trials really different?
Good recruitment is integral to the conduct of a high-quality randomised controlled trial. It has been suggested that recruitment is particularly difficult for evaluations of surgical interventions, a field in which there is a dearth of evidence from randomised comparisons. While there is anecdotal speculation to support the inference that recruitment to surgical trials is more challenging than for medical trials we are unaware of any formal assessment of this. In this paper, we compare recruitment to surgical and medical trials using a cohort of publicly funded trials. Overall recruitment to trials was assessed using of a cohort of publicly funded trials (n=114). Comparisons were made by using the Recruitment Index, a simple measure of recruitment activity for multicentre randomised controlled trials. Recruitment at the centre level was also investigated through three example surgical trials. The Recruitment Index was found to be higher, though not statistically significantly, in the surgical group (n=18, median=38.0 IQR (10.7, 77.4)) versus (n=81, median=34.8 IQR (11.7, 98.0)) days per recruit for the medical group (median difference 1.7 (-19.2, 25.1); p=0.828). For the trials where the comparison was between a surgical and a medical intervention, the Recruitment Index was substantially higher (n=6, 68.3 (23.5, 294.8)) versus (n=93, 34.6 (11.7, 90.0); median difference 25.9 (-35.5, 221.8); p=0.291) for the other trials. There was no clear evidence that surgical trials differ from medical trials in terms of recruitment activity. There was, however, support for the inference that medical versus surgical trials are more difficult to recruit to. Formal exploration of the recruitment data through a modelling approach may go some way to tease out where important differences exist.


Functional physiology of the human terminal antrum defined by high-resolution electrical mapping and computational modeling.
High-resolution (HR) mapping has been used to study gastric slow-wave activation; however, the specific characteristics of antral electrophysiology remain poorly defined. This study applied HR mapping and computational modeling to define functional human antral physiology. HR mapping was performed in 10 subjects using flexible electrode arrays (128-192 electrodes; 16-24 cm2) arranged from the pylorus to mid-corpus. Anatomical registration was by photographs and anatomical landmarks. Slow-wave parameters were computed, and resultant data were incorporated into a computational fluid dynamics (CFD) model of gastric flow to calculate impact on gastric mixing. In all subjects, extracellular mapping demonstrated normal aboral slow-wave propagation and a region of increased amplitude and velocity in the prepyloric antrum. On average, the high-velocity region commenced 28 mm proximal to the pylorus, and activation ceased 6 mm from the pylorus. Within this region, velocity increased 0.2 mm/s per mm of tissue, from the mean 3.3 ± 0.1 mm/s to 7.5 ± 0.6 mm/s (P < 0.001), and extracellular amplitude increased from 1.5 ± 0.1 mV to 2.5 ± 0.1 mV (P < 0.001). CFD modeling using representative parameters quantified a marked increase in antral recirculation, resulting in an enhanced gastric mixing, due to the accelerating terminal antral contraction. The extent of gastric mixing increased almost linearly with the maximal velocity of the contraction. In conclusion, the human terminal antral contraction is controlled by a short region of rapid high-amplitude slow-wave activity. Distal antral wave acceleration plays a major role in antral flow and mixing, increasing particle strain and trituration.


Using community/researcher partnerships to develop a culturally relevant intervention for children with communication disabilities in Kenya.
The objective of this study is to develop a culturally relevant community-based intervention for children with communication disabilities in Kenya through a community/researcher partnership. The resulting intervention is for use in a randomized control trial which will be reported at a later stage. Using a qualitative approach, initial data was collected through focus group discussions with women, disabled people and traditional dancers. The groups examined the needs, problems and challenges faced by disabled children and their families. This generated the content and structure for a series of participatory workshops with a further two women's groups. These workshops strove to generate a culturally relevant community-based intervention programme for children with communication disabilities and their families. The content and balance of the resulting intervention was observed to be different from existing programmes described in the literature. Notably it included many culturally appropriate strategies for increasing social integration and raising community awareness. The process of generating a locally relevant community-based rehabilitation intervention is potentially transferable and has particular relevance to the estimated 80% of the world where there are no formal rehabilitation services for children with disabilities and where women's groups are a strong element of local culture. (i) Community/researcher partnerships can be used to develop interventions; (ii) such interventions are different from those imported from other cultures; and (iii) this process is transferable and can be part of the preparations for a Randomized Control Trial.


A comparison of photoplethysmography and ECG recording to analyse heart rate variability in healthy subjects.
Measures of heart rate variability (HRV) are widely used to assess autonomic nervous system (ANS) function. The signal from which they are derived requires accurate determination of the interval between successive heartbeats; it can be recorded via electrocardiography (ECG), which is both non-invasive and widely available. However, methodological problems inherent in the recording and analysis of ECG traces have motivated a search for alternatives. Photoplethysmography (PPG) constitutes another means of determining the timing of cardiac cycles via continuous monitoring of changes in blood volume in a portion of the peripheral microvasculature. This technique measures pulse waveforms, which in some instances may prove a practical basis for HRV analysis. We investigated the feasibility of using earlobe PPG to analyse HRV by applying the same analytic process to PPG and ECG recordings made simultaneously. Comparison of 5-minute recordings demonstrated a very high degree of correlation in the temporal and frequency domains and in nonlinear dynamic analyses between HRV measures derived from PPG and ECG. Our results confirm that PPG provides accurate interpulse intervals from which HRV measures can be accurately derived in healthy subjects under ideal conditions, suggesting this technique may prove a practical alternative to ECG for HRV analysis. This finding is of particular relevance to the care of patients suffering from peripheral hyperkinesia or tremor, which make fingertip PPG recording impractical, and following clinical interventions known to introduce electrical artefacts into the electrocardiogram.


Cross-resistance relationships between neonicotinoids and pymetrozine in Bemisia tabaci (Hemiptera: Aleyrodidae).
Although cross-resistance between compounds in the same insecticide group is a frequently observed phenomenon, cross-resistance between groups that differ in structural and functional characteristics can be extremely unpredictable. In the case of controlling the whitefly, Bemisia tabaci Gennadius, neonicotinoids and the pyridine azomethine antifeedant pymetrozine represent independent lines of discovery that should be suited for alternation to avoid prolonged selection for the same resistance mechanism. Reports of an association between responses to neonicotinoids and pymetrozine were investigated by resistance profiling of seven B. tabaci strains and complementary reciprocal selection experiments. All strains demonstrated a consistent correlation between responses to three neonicotinoid compounds: thiamethoxam, imidacloprid and acetamiprid. Responses to neonicotinoids for six field strains clearly correlated with responses to pymetrozine. Reciprocal selection experiments confirmed an unexpected case of intergroup cross-resistance. A seventh strain exhibited a so far unique phenotype of strong resistance to pymetrozine but full susceptibility to neonicotinoids. Selection experiments confirmed that in this strain the mechanism of pymetrozine resistance is specific and has no implications for neonicotinoids. Cross-resistance between neonicotinoids and pymetrozine in B. tabaci probably reflects the overexpression of a cytochrome-P450-dependent monooxygenase capable of metabolising both types of compound in spite of their apparent structural dissimilarity. Given the predominance of this mechanism in B. tabaci, both can contribute to resistance management but should be placed within the same treatment 'window'.


Photobiomodulation with Near Infrared Light Helmet in a Pilot, Placebo Controlled Clinical Trial in Dementia Patients Testing Memory and Cognition.
Alzheimer's disease (AD) is a common, chronic expensive debilitating neurodegenerative disease with no current treatments to prevent the physical deterioration of the brain and the consequent cognitive deficits. The current pathophysiology of Alzheimer's disease is the accumulation of neurofibrillary tangles (NFTs) of hyperphosphorylated tau protein and amyloid-beta (Aβ) plaques. Antibody therapy of Tau and Amyloid beta, vaccines and other methods to decrease Tau and or Amyloid have not been successful after considerable pharmaceutical and biotech efforts. For example, Eli Lilly announced a major change to its closely watched clinical trial for the Alzheimer's drug solanezumab which failed to reach statistical significance. Recently, a report on animal models using photomodulation with near infrared light to treat AD pathology in K369I tau transgenic model (K3) l engineered to develop neurofibrillary tangles, and the APPs/PSEN1dE9 transgenic model (APP/PS1) to develop amyloid plaques. Mice were treated with NIR 20 times over a four-week period and NIR treatment (600-1000 nm) was associated with a reduction in the size and number of amyloid-β plaques in the neocortex and hippocampus. We now report a small pilot double blind, placebo-controlled trial (n=11) 6 active, 3 controls and 2 dropouts assessing the effect of 28 consecutive, sixminute transcranial sessions of near infrared (NIR) stimulation using 1060-1080 nm light emitting diodes. Subjects were independently diagnosed with dementia conducted in an outpatient behavioral healthcare clinic. IRB approval was obtained through the Quietmind Foundation's institutional review Board (IRB). Results showed changes in executive functioning; clock drawing, immediate recall, praxis memory, visual attention and task switching (Trails A&B) as well as a trend of improved EEG amplitude and connectivity measures. Neuroplasticity has also been reported with NIR light stimulation and mitochondrial enhancement.


Accelerated long-term forgetting in presymptomatic autosomal dominant Alzheimer's disease: a cross-sectional study.
Tests sensitive to presymptomatic changes in Alzheimer's disease could be valuable for clinical trials. Accelerated long-term forgetting-during which memory impairment becomes apparent over longer periods than usually assessed, despite normal performance on standard cognitive testing-has been identified in other temporal lobe disorders. We assessed whether accelerated long-term forgetting is a feature of presymptomatic autosomal dominant (familial) Alzheimer's disease, and whether there is an association between accelerated long-term forgetting and early subjective memory changes. This was a cross-sectional study at the Dementia Research Centre, University College London (London, UK). Participants were recruited from a cohort of autosomal dominant Alzheimer's disease families already involved in research at University College London, and had to have a parent known to be affected by an autosomal dominant Alzheimer's disease mutation, and not report any current symptoms of cognitive decline. Accelerated long-term forgetting of three tasks (list, story, and figure recall) was assessed by comparing 7-day recall with initial learning and 30-min recall. 7-day recognition was also assessed. Subjective memory was assessed using the Everyday Memory Questionnaire. The primary outcome measure for each task was the proportion of material retained at 30 min that was recalled 7 days later (ie, 7-day recall divided by 30-min recall). We used linear regression to compare accelerated long-term forgetting scores between mutation carriers and non-carriers (adjusting for age, IQ, and test set) and, for mutation carriers, to assess whether there was an association between accelerated long-term forgetting and estimated years to symptom onset (EYO). Spearman's correlation was used to examine the association between accelerated long-term forgetting and subjective memory scores. Between Feb 17, 2015 and March 30, 2016, we recruited 35 people. 21 participants were mutation carriers (mean EYO 7·2 years, SD 4·5). Across the three tasks, we detected no differences between carriers and non-carriers for initial learning or 30-min recall. The proportion of material recalled at 7 days was lower in carriers than non-carriers for list (estimated difference in mean for list recall -30·94 percentage points, 95% CI -45·16 to -16·73; p=0·0002), story (-20·10, -33·28 to -6·91; p=0·0048), and figure (-15·41, -26·88 to -3·93; p=0·012) recall. Accelerated long-term forgetting was greater in carriers nearer to their estimated age at onset (p≤0·01 for all three tests). Mutation carriers' 7-day recognition memory was also lower across all tasks (list [mean difference -5·80, 95% CI -9·96 to -2·47; p<0·01], story [-6·84, -10·94 to -3·37; p<0·01], and figure [-17·61, -27·68 to -7·72; p<0·01] recognition). Subjective memory scores were poorer in asymptomatic carriers compared with non-carriers (adjusted difference in means 7·88, 95% CI 1·36 to 14·41; p=0·016), and we found a correlation between accelerated long-term forgetting and subjective memory in mutation carriers. Accelerated long-term forgetting is an early presymptomatic feature of autosomal dominant Alzheimer's disease, which appears to pre-date other amnestic deficits and might underpin subjective memory complaints in Alzheimer's disease. Accelerated long-term forgetting testing might be useful in presymptomatic Alzheimer's disease trials. MRC, NIHR, Alzheimer's Research UK, Dementias Platform UK, Dunhill Medical Trust, ERUK, Great Western Research, Health Foundation, Patrick Berthoud Trust.


Neutralizing IL-12 during induction of murine acute graft-versus-host disease polarizes the cytokine profile toward a Th2-type alloimmune response and confers long term protection from disease.
Injection of parental spleen cells into BDF1 mice results in a graft-vs-host disease (GVHD), the nature of which is critically dependent on the parental haplotype. B6-->BDF1 mice develop a Th1-mediated immunosuppressive lethal GVHD, whereas DBA/2-->BDF1 mice develop a Th2-dependent chronic GVHD, characterized by autoantibody production and glomerulonephritis. In this study we show that neutralizing endogenous IL-12 for a brief period during the initiation of acute GVHD in B6-->BDF1 mice not only confers long term protection from the acute disease, but also permits full repopulation of the recipient with donor B6 lymphocytes. Antibody-treated animals showed normal T cell proliferation in response to Con A stimulation and remained healthy throughout the study. Splenocytes from such mice showed reduced in vitro production of IFN-gamma and enhanced production of IL-5 and IL-10, suggesting a permanent switch from a Th1 to a Th2 cytokine response, comparable to that associated with chronic GVHD in DBA/2-->BDF1 mice. In contrast to DBA/2-->BDF1 mice, however, anti-IL-12-treated B6-->BDF1 mice displayed only mild B cell hyper-responsiveness, as evidenced by a modest increase in serum IgG and IgE levels and moderate levels of anti-dsDNA Abs. Importantly, however, anti-IL-12-treated B6-->BDF1 mice showed no evidence of immune complex-mediated glomerulonephritis. These results demonstrate that neutralizing IL-12 is an effective means of preventing acute GVHD and does not result in the development of chronic GVHD, which might otherwise limit its application.


An overview of recent findings of the Stanley Foundation Bipolar Network (Part I).
Selected recent findings of the Stanley Foundation Bipolar Network are briefly reviewed and their clinical implications discussed. Daily prospective ratings on the NIMH-LCM indicate a high degree of residual depressive morbidity (three times that of hypomania or mania) despite active psychopharmacological treatment with a variety of modalities including mood stabilizers, antidepressants, and benzodiazepines, as well as antipsychotics as necessary. The rates of switching into brief to full hypomania or mania during the use of antidepressants is described, and new data suggesting the potential utility of continuing antidepressants in the small group of patients showing an initial acute and persistent response is noted. Bipolar patients with a history of major environmental adversities in childhood have a more severe course of illness and an increased incidence of suicide attempts compared with those without. Preliminary open data suggest useful antidepressant effects of the atypical antipsychotic quetiapine, while a double-blind randomized controlled study failed to show efficacy of omega-3 fatty acids (6 g of eicosapentaenoic acid compared with placebo for 4 months) in the treatment of either acute depression or rapid cycling. The high prevalence of overweight and increased incidence of antithyroid antibodies in patients with bipolar illness is highlighted. Together, these findings suggest a very high degree of comorbidity and treatment resistance in outpatients with bipolar illness treated in academic settings and the need to develop not only new treatment approaches, but also much earlier illness recognition, diagnosis, and intervention in an attempt to reverse or prevent this illness burden.


Overview of the principal results and secondary analyses from the European and North American randomised trials of endarterectomy for symptomatic carotid stenosis.
Review of the primary results and secondary analyses from the European Carotid Surgery Trial (ECST) and the North American Symptomatic Carotid Endarterectomy Trial (NASCET). Review of 48 ECST and NASCET papers. The simple assumption that all patients with a symptomatic stenosis >70% benefit from CEA is untenable. Approximately 70-75% will not have a stroke if treated medically. The ECST and NASCET have identified subgroups that should have expedited investigation and surgery (male sex, age >75 years, 90-99% stenosis, irregular plaque, hemispheric symptoms, recurrent events for >6 months, contralateral occlusion, multiple co-morbidity). Accordingly development of local protocols for patient selection/exclusion should involve surgeons and physicians and take account of the local operative risk. The ECST and NASCET have also shown that the ubiquitous "string sign" is not associated with a high risk of stroke, and emergency CEA is unnecessary. Surgeons must quote their own results and be aware that a high operative risk reduces long-term benefit. Accordingly, in those centres with a higher operative death/stroke rate, some "lower risk" patients should probably be considered for best medical therapy alone. It is hoped that pooling of the ECST and NASCET databases will enable more definitive guidelines to be developed regarding who benefits most from CEA.


Persistent amyloidosis following suppression of Abeta production in a transgenic model of Alzheimer disease.
The proteases (secretases) that cleave amyloid-beta (Abeta) peptide from the amyloid precursor protein (APP) have been the focus of considerable investigation in the development of treatments for Alzheimer disease. The prediction has been that reducing Abeta production in the brain, even after the onset of clinical symptoms and the development of associated pathology, will facilitate the repair of damaged tissue and removal of amyloid lesions. However, no long-term studies using animal models of amyloid pathology have yet been performed to test this hypothesis. We have generated a transgenic mouse model that genetically mimics the arrest of Abeta production expected from treatment with secretase inhibitors. These mice overexpress mutant APP from a vector that can be regulated by doxycycline. Under normal conditions, high-level expression of APP quickly induces fulminant amyloid pathology. We show that doxycycline administration inhibits transgenic APP expression by greater than 95% and reduces Abeta production to levels found in nontransgenic mice. Suppression of transgenic Abeta synthesis in this model abruptly halts the progression of amyloid pathology. However, formation and disaggregation of amyloid deposits appear to be in disequilibrium as the plaques require far longer to disperse than to assemble. Mice in which APP synthesis was suppressed for as long as 6 mo after the formation of Abeta deposits retain a considerable amyloid load, with little sign of active clearance. This study demonstrates that amyloid lesions in transgenic mice are highly stable structures in vivo that are slow to disaggregate. Our findings suggest that arresting Abeta production in patients with Alzheimer disease should halt the progression of pathology, but that early treatment may be imperative, as it appears that amyloid deposits, once formed, will require additional intervention to clear.


Virologic failure and HIV drug resistance on simplified, dolutegravir-based maintenance therapy: Systematic review and meta-analysis.
Background: Dolutegravir-containing maintenance therapy is a promising simplification strategy for virologically suppressed HIV-infected individuals. However, most of the available data to inform this strategy come from small, uncontrolled studies. We estimated the proportion of HIV-infected patients experiencing virological failure (VF) and developing drug resistance on dolutegravir (DTG)-based maintenance therapy. Methods: We searched Medline, Embase, Cochrane Central, Web of Science, and conference abstracts for studies assessing VF on DTG-based maintenance therapy. Studies including ≥5 adults with an undetectable viral load on antiretroviral therapy (ART) who switched to a DTG-based mono- or dual therapy were included. Pooled proportions of VF were estimated using random-intercept logistic meta-regression and acquired drug resistance mutations described for each strategy. Results: Of 1719 studies considered, 21 met our selection criteria, including seven interventional and 14 observational studies. Eight studies including 251 patients assessed VF on DTG monotherapy and fourteen studies including 1670 participants VF on dual therapy. The participant's median age ranged from 43 to 63 years, their median nadir CD4 count from 90 to 399 cells/µl, and 27.6% were female. The proportion of participants experiencing VF on DTG-monotherapy was 3.6% (95% confidence interval [CI] 1.9-6.7) at 24 weeks and 8.9% (95% CI 4.7-16.2) at 48 weeks. Resistance mutations developed in seven (3.6%) participants on DTG-monotherapy. Among patients on dual therapy, ten (0.7%, 95% CI 0.4-1.3) experienced VF by 48 weeks and none developed resistance to DTG. In adjusted analyses, VF at 24 weeks was less likely on dual therapy than on monotherapy (adjusted odds ratio: 0.10, 95% CI 0.03-0.30). Conclusions: Whereas VF is relatively common on DTG maintenance monotherapy, DTG-based dual therapy appears to be a promising simplification strategy for individuals with a suppressed HIV viral load on triple-ART.


Community pharmacists' interest in and attitude to pharmacy practice research in Ethiopia: A cross-sectional study.
Pharmacy practice-research became an important component in the pharmacy practice. However, limited studies were conducted in sub-Saharan Africa to understand the pharmacists' interest and attitude towards pharmacy practice-research. We aimed to assess the community pharmacists' interest and attitude towards pharmacy practice-research in Ethiopia. A cross-sectional survey was conducted among community pharmacists in eight major cities in Ethiopia. A validated 25-item self-administered questionnaire covering interest and attitude related to pharmacy practice-research was distributed. Responses were analysed using descriptive and inferential statistics. A total of 389 community pharmacists responded to the survey (response rate- 88.4%). Most of community pharmacists showed a high level of interest and positive attitude in being involved in all aspects of pharmacy practice-research. The median summary score for interest and attitude were 38 (IQR 20-40) (range possible 10-50) and 30 (IQR 18-39), respectively. Sixty-seven percent of the respondents thought about being involved in research, felt research is important for their career (57.6%), confident to conduct the research (56.2%), and agreed that research is a part of pharmacy practice (48.5%). However, only forty-six percent agreed that they underwent research training. A multivariate analysis showed that females were more interested in pharmacy practice research than males [AOR: 1.50, 95% CI: 0.99-2.27; p<0.05]. Community pharmacists showed high interest towards several areas of research competencies and demonstrated positive attitude towards pharmacy practice-research. Our findings suggest that providing research training to community pharmacists may contribute in undertaking research activities and build the research capacity in Ethiopia.


Preserved foods and nasopharyngeal carcinoma: a case-control study in Guangxi, China.
One hundred twenty-eight mothers of nasopharyngeal carcinoma (NPC) cases under age 45 in Yulin Prefecture, China and 174 mothers of population controls were interviewed as part of an epidemiological study to examine childhood exposures in relation to the development of NPC. Exposure before age 2 years to a number of fermented foods was a risk factor for NPC. During weaning, intake of salted fish [relative risk (RR) = 2.6, one-sided P (P) = 0.01], salted duck eggs (RR = 5.0, P = 0.03), salted mustard green (RR = 5.4, P = 0.03), and chung choi (RR = 2.0), P = 0.003), a kind of salted root, was significantly related to an increased risk of NPC. Between ages 1 and 2 years, intake frequency of dried fish [P for linear trend test (linear trend P) = 0.002], fermented black bean paste (linear trend P = 0.0009), and fermented soy bean paste (linear trend P = 0.007) was also positively associated with NPC. A multivariate analysis of these different foods showed all except fermented black bean paste to be independently related to NPC.


Human IgG Fc receptor II mediates antibody-dependent enhancement of dengue virus infection.
It is known that anti-dengue virus antibodies at subneutralizing concentrations augment dengue virus infection of IgG FcR (Fc gamma R)-positive cells, and this phenomenon is called antibody-dependent enhancement. This is caused by the uptake of dengue virus-antibody complexes by Fc gamma R. We previously reported that Fc gamma RI can mediate antibody-dependent enhancement. In this study we use an erythroleukemia cell line, K562, which has Fc gamma RII, but does not have Fc gamma RI or Fc gamma RIII, to determine if Fc gamma RII can mediate infection by dengue virus-antibody complexes. Polyclonal mouse anti-dengue virus antibody significantly augments dengue virus infection of K562 cells, whereas normal mouse serum does not. A mAb IV.3, which is specific for Fc gamma RII and is known to inhibit the binding of Ag-antibody complex to Fc gamma RII, inhibits dengue antibody-mediated augmentation of dengue virus infection. It has been reported that Fc gamma RII binds to mouse IgG1, but not to mouse IgG2a. A mouse IgG1 anti-dengue virus mAb (3H5) augments dengue virus infection of K562 cells, but a mouse IgG2a anti-dengue virus mAb (4G2) does not. 4G2 augments dengue virus infection of a human monocytic cell line, U937, which has Fc gamma RI. Based on these results we conclude that Fc gamma RII mediate antibody-dependent enhancement of dengue virus infection in addition to Fc gamma RI.


The role of sodium carbonate in PAM coagulation-flocculation for oil acidized wastewater treatment.
The pH value of oil acidized wastewater is relatively low (pH = 6.1), which seriously affects the flocculation of polyacrylamide (PAM). NaOH was used to adjust the pH value, but the maximum was only 7.5. The regulation was limited as the Ca2+ in aqueous phase up to 1,350 mg L-1 consumed OH-. A novel formulation of Na2CO3 + PAM was proposed to form CaCO3 floc core to facilitate PAM coagulation. When the concentration was above 400 mg L-1, the PAM precipitation tended to be maximum, followed by NaOH adjustment of pH to 8.0 that could enhance PAM flocculation successively. The sewage sludge (SS) remained and residue oil reduced to 25 mg L-1 and 34mg L-1 respectively. The analysis of the species and composition of fatty acids indicated that the coagulation-flocculation selectively effected the sedimentation of saturated fatty acids (SAT). This provides a new idea for recovery of high value-added residual oil. The optimal additive of Na2CO3 is expected as promising coagulant aid to improve the PAM coagulation-flocculation of oil acidized wastewater.


Isolation and characterization of human monoclonal autoantibodies to glutamic acid decarboxylase.
Production of human monoclonal autoantibodies to glutamic acid decarboxylase M(r) 65,000 (GAD65), characterization of their isotype, binding affinity, V region sequences and competition with autoantibodies in patients' sera is described. Lymphocytes from a patient with Addison's disease who had GAD65 autoantibodies without diabetes were immortalised and fused to a mouse/human hybridoma. In addition, mouse monoclonal antibodies to GAD65 were produced using standard techniques. F(ab')2S from our monoclonals and the GAD6 mouse monoclonal were used in competition with intact monoclonals and sera from diabetic patients for binding to 125I-labelled GAD65 (amino acids 46-586). Reactivities of the human monoclonals with GAD 65,000/67,000 M(r) chimeras were also studied. Variable region genes of human monoclonals were sequenced and analysed. The human monoclonals (n = 3) had affinity constants for GAD65 of 2.2 x 10(9), 5.8 x 10(9), 1.3 x 10(10) mol/l(-1); affinities of the mouse monoclonals (n = 5) ranged from 1.1 x 10(8) to 5.4 x 10(10) mol/l(-1). The binding of each of the human monoclonals was inhibited by GAD6 F(ab')2 and the binding of GAD6 antibody was inhibited by the human monoclonal F(ab')2S suggesting that the epitopes for these antibodies were overlapping. Studies with GAD65/GAD67 chimeras indicated that the human monoclonals reacted with C-terminal epitopes. The human monoclonals, GAD6 and 3/5 mouse monoclonals inhibited serum autoantibody binding to 125I-labelled GAD65. Overall, the human monoclonals were of high affinity, reacted with C-terminal epitopes and showed evidence of antigen driven maturation; they represented only a proportion of the repertoire of autoantibodies to GAD65 in the donor's serum and in the sera of patients with type-1 diabetes.


Framing international trade and chronic disease.
There is an emerging evidence base that global trade is linked with the rise of chronic disease in many low and middle-income countries (LMICs). This linkage is associated, in part, with the global diffusion of unhealthy lifestyles and health damaging products posing a particular challenge to countries still facing high burdens of communicable disease. We developed a generic framework which depicts the determinants and pathways connecting global trade with chronic disease. We then applied this framework to three key risk factors for chronic disease: unhealthy diets, alcohol, and tobacco. This led to specific 'product pathways', which can be further refined and used by health policy-makers to engage with their country's trade policy-makers around health impacts of ongoing trade treaty negotiations, and by researchers to continue refining an evidence base on how global trade is affecting patterns of chronic disease. The prevention and treatment of chronic diseases is now rising on global policy agendas, highlighted by the UN Summit on Noncommunicable Diseases (September 2011). Briefs and declarations leading up to this Summit reference the role of globalization and trade in the spread of risk factors for these diseases, but emphasis is placed on interventions to change health behaviours and on voluntary corporate responsibility. The findings summarized in this article imply the need for a more concerted approach to regulate trade-related risk factors and thus more engagement between health and trade policy sectors within and between nations. An explicit recognition of the role of trade policies in the spread of noncommunicable disease risk factors should be a minimum outcome of the September 2011 Summit, with a commitment to ensure that future trade treaties do not increase such risks.


Understanding the impact of an intergenerational arts and health project: a study into the psychological well-being of participants, carers and artists.
There is growing interest in arts practices in relation to public health, including their potential to support psychological well-being. This study sought to understand the impact of Hear and Now, an intergenerational arts and health project, upon indicators of psychological well-being among all groups involved: young people, older people with a diagnosis of dementia and their carers and partners and the project's artistic team. This was a descriptive exploratory qualitative study, using focus groups and observation as data collection methods. Study participants were 65 people representing the four groups participating in the 2019 Hear and Now project: older adults living with a diagnosis of dementia, their carers and partners, young people and a team of professional artists and facilitators. Of these, 27 participated in one or more of seven focus groups. Participants were asked about their previous engagement with music and dance, thoughts about the intergenerational element of the project and other aspects of their experiences that related to indicators of well-being. In order to investigate the project's impact on participants' well-being, Seligman's PERMA model was adopted, which sets out five indicators of well-being: positive emotions, engagement, positive relationships, meaning and achievement/accomplishment. Experiences relating to all five areas of the PERMA model were evidenced by all groups in relation to their involvement in the project. Additional health benefits were also cited by some, as well as enhanced perceptions of other members of the project cohort. The findings support existing literature that intergenerational and arts activities can be beneficial for individuals' psychological health. Experiences relating to all five dimensions of the PERMA model of well-being (positive emotion, engagement, positive relationships, meaning, achievement/accomplishment) were cited by the four participant groups, which suggests examining the impact of such projects on all project collaborators is worthy of further study. Understanding the impact these projects can have on the various groups involved will enable artistic and healthcare communities to better collaborate and value each other's practices.


Perception of second- and third-order orientation signals and their interactions.
Orientation signals, which are crucial to many aspects of visual function, are more complex and varied in the natural world than in the stimuli typically used for laboratory investigation. Gratings and lines have a single orientation, but in natural stimuli, local features have multiple orientations, and multiple orientations can occur even at the same location. Moreover, orientation cues can arise not only from pairwise spatial correlations, but from higher-order ones as well. To investigate these orientation cues and how they interact, we examined segmentation performance for visual textures in which the strengths of different kinds of orientation cues were varied independently, while controlling potential confounds such as differences in luminance statistics. Second-order cues (the kind present in gratings) at different orientations are largely processed independently: There is no cancellation of positive and negative signals at orientations that differ by 45°. Third-order orientation cues are readily detected and interact only minimally with second-order cues. However, they combine across orientations in a different way: Positive and negative signals largely cancel if the orientations differ by 90°. Two additional elements are superimposed on this picture. First, corners play a special role. When second-order orientation cues combine to produce corners, they provide a stronger signal for texture segregation than can be accounted for by their individual effects. Second, while the object versus background distinction does not influence processing of second-order orientation cues, this distinction influences the processing of third-order orientation cues.


Effect of early maternal separation stress on attention, spatial learning and social interaction behaviour.
Early life stress is known to influence affective and cognitive functions in later life but comprehensive explanation for the impact of early life stress on attentional functions, behavioural control and social behaviour is inadequate. The early life stress was induced by exposing rat pups to 6 h of maternal separation and isolation (MS) stress from postnatal days 4-14 i.e. during SHRP period. The long-term impact of MS in these rats was evaluated by assessing anxiety, sociability, social preference, spatial learning and memory along with a detailed evaluation of attentional functions during young adulthood period. Adult male MS rats showed increased anxiety-like behaviour, impaired flexibility in social interactions, and increased reward-seeking behaviour. MS rats also showed faster spatial learning in the partially baited radial arm maze and exhibited moderately enhanced sustained attention in the 5-choice serial reaction time task (5CSRTT). These results suggest that early MS has both positive and negative consequences in adulthood. Increased cognitive ability in MS rats, as evidenced by the improved sustained attention and spatial learning and memory, is usually advantageous and indicates positive influences of early stressors that might lead to the development of resilience and enhanced compensatory mechanisms later in adulthood. MS stress has compromised flexibility in social behaviour that promotes solitary lifestyle and social isolation. Heightened reward-seeking behaviour, as shown by the MS rats, could be a predisposing factor for substance abuse and addiction. Thus, our study highlights the crucial and differential impact of early life challenges on behaviour during adulthood and suggests that the positive aspects could be an asset that may be utilized to suppress the negative effects of early life stress in adulthood.


Sclerosing lipogranuloma of the eyelid: unusual complication following nasal packing in endoscopic sinus surgery.
An eyelid or orbital lipogranuloma can occur following nasal packing with liquid paraffin, petroleum jelly or an antibiotic-based cream. It usually presents a few weeks or months after the initial procedure. We present a report of three such cases of sclerosing lipogranuloma involving the eyelid, which occurred following a sinonasal surgery where nasal packing using petroleum jelly was performed. The typical clinical course and the classical histopathological features are highlighted. All cases were diagnosed by histopathological examination as sclerosing lipogranuloma. Complete surgical removal resulted in complete resolution on 1 month follow-up. The diagnosis is based on a high degree of suspicion following a detailed history of prior use of lipid-based products for nasal packing following endonasal surgery. Histopathology is diagnostic. Surgical excision is the treatment of choice, however, due to its infiltrative nature, it may be difficult to obtain a complete cure.


Repetition effects in word and pseudoword identification: comment on Salasoo, Shiffrin, and Feustel.
Two recent articles by Feustel, Shiffrin, and Salasoo (1983) and Salasoo, Shiffrin, and Feustel (1985) argue that word identification is based on episodic memory as well as semantic (or "permanent, abstract") memory. The earlier article argued for separate processing stages affected by repetition (episodic memory) and lexicality (semantic memory). To account for the new finding that number of repetitions interacts with lexicality, the later article invokes the same two types of memory, operating in parallel rather than serially. We argue that Salasoo et al.'s data are compatible with a wide variety of competing theories, including some that do not involve episodic memory at all. We question the relevance of a complex formal model shown by the authors to account for the main trends in the data, because it makes little use of key properties of episodic memory. Furthermore, we show that two variants of a less complex model inspired by logogen theory fit the data as well or better than the model of Salasoo et al., using fewer free parameters. We argue that what is needed is not an existence proof that one particular complex model can fit a body of data, but experimental manipulations that successfully discriminate between broad classes of competing theories.


Effects of a mindfulness-based intervention during pregnancy on prenatal stress and mood: results of a pilot study.
Stress and negative mood during pregnancy increase risk for poor childbirth outcomes and postnatal mood problems and may interfere with mother-infant attachment and child development. However, relatively little research has focused on the efficacy of psychosocial interventions to reduce stress and negative mood during pregnancy. In this study, we developed and pilot tested an eight-week mindfulness-based intervention directed toward reducing stress and improving mood in pregnancy and early postpartum. We then conducted a small randomized trial (n=31) comparing women who received the intervention during the last half of their pregnancy to a wait-list control group. Measures of perceived stress, positive and negative affect, depressed and anxious mood, and affect regulation were collected prior to, immediately following, and three months after the intervention (postpartum). Mothers who received the intervention showed significantly reduced anxiety (effect size, 0.89; p<0.05) and negative affect (effect size, 0.83; p<0.05) during the third trimester in comparison to those who did not receive the intervention. The brief and nonpharmaceutical nature of this intervention makes it a promising candidate for use during pregnancy.


Paramedic rapid sequence induction (RSI) in a South African emergency medical service: a retrospective observational study.
Early access to critical care interventions may improve outcomes for severely ill and injured patients. South Africa (SA) faces the unique challenges of prolonged pre-hospital times and limited access to physicians. In 2008, the Health Professions Council of SA introduced paramedic rapid sequence induction (RSI), the gold standard critical care intervention for emergency airway management; however, the risk to benefit ratio in this context is unclear. We conducted a pilot study to identify if paramedic RSI in the SA pre-hospital care setting is effective and safe. We undertook a retrospective observational study of paramedic RSI performed by an emergency medical service, between 12 December 2009 and 12 December 2011. Eighty-six RSIs were performed during the study period. No failed intubations were reported. Heart rate was significantly reduced from a median baseline value of 112 to 90 bpm, and oxygen saturations improved from 92% to 99% at handover following RSI. Nineteen patients (22%), however, had an adverse event (AE). Female patients (odds ratio (OR) 18.3; 95% confidence interval (CI) 3.46 - 99.38; p=0.001) and patients subsequently transported by helicopter (OR 7.24; 95% CI 1.44 - 36.32; p=0.016) remained independently associated with AEs after adjusting for confounders. RSI performed by specially trained paramedics is effective in terms of self-reported success. However, the 1 in 5 AE rate highlights safety concerns. The importance of a robust clinical governance programme to identify problems, refine practice and improve the quality of care is underscored.


One-Stage versus Two-Stage Repair of Asymmetric Bilateral Cleft Lip: A 20-Year Retrospective Study of Clinical Outcome.
Both one- and two-stage approaches have been widely used for patients with asymmetric bilateral cleft lip. There are insufficient long-term outcome data for comparison of these two methods. The purpose of this retrospective study was to compare the clinical outcome over the past 20 years. The senior author's (L.J.L.) database was searched for patients with asymmetric bilateral cleft lip from 1995 to 2015. Qualified patients were divided into two groups: one-stage and two-stage. The postoperative photographs of patients were evaluated subjectively by surgical professionals and laypersons. Ratios of the nasolabial region were calculated for objective analysis. Finally, the revision procedures in the nasolabial area were reviewed. Statistical analyses were performed. A total of 95 consecutive patients were qualified for evaluation. Average follow-up was 13.1 years. A two-stage method was used in 35 percent of the patients, and a one-stage approach was used in 65 percent. All underwent primary nasal reconstruction. Among the satisfaction rating scores, the one-stage repair was rated significantly higher than two-stage reconstruction (p = 0.0001). Long-term outcomes of the two-stage patients and the unrepaired mini-microform deformities were unsatisfactory according to both professional and nonprofessional evaluators. The revision rate was higher in patients with a greater-side complete cleft lip and palate as compared with those without palatal involvement. The results suggested that one-stage repair provided better results with regard to achieving a more symmetric and smooth lip and nose after primary reconstruction. The revision rate was slightly higher in the two-stage patient group. Therapeutic, III.


TREM2 triggers microglial density and age-related neuronal loss.
The microglial triggering receptor expressed on myeloid cells 2 (TREM2) signals via the activatory membrane adaptor molecule TYROBP. Genetic variants or mutations of TREM2 or TYROBP have been linked to inflammatory neurodegenerative diseases associated with aging. The typical aging process goes along with microglial changes and mild neuronal loss, but the exact contribution of TREM2 is still unclear. Aged TREM2 knock-out mice showed decreased age-related neuronal loss in the substantia nigra and the hippocampus. Transcriptomic analysis of the brains of 24 months old TREM2 knock-out mice revealed 211 differentially expressed genes mostly downregulated and associated with complement activation and oxidative stress response pathways. Consistently, 24 months old TREM2 knock-out mice showed lower transcription of microglial (Aif1 and Tmem119), oxidative stress markers (Inos, Cyba, and Cybb) and complement components (C1qa, C1qb, C1qc, C3, C4b, Itgam, and Itgb2), decreased microglial numbers and expression of the microglial activation marker Cd68, as well as accumulation of oxidized lipids. Cultured microglia of TREM2 knock-out mice showed reduced phagocytosis and oxidative burst. Thus, microglial TREM2 contributes to age-related microglial changes, phagocytic oxidative burst, and loss of neurons with possible detrimental effects during physiological aging.


Association of circulating osteocalcin with cardiovascular disease and intermediate cardiovascular phenotypes: systematic review and meta-analysis.
Objectives. Circulating osteocalcin (OC), a marker which is central in bone mineralization, may be involved in the atherosclerotic process and influence the risk of developing cardiovascular disease (CVD). We conducted a systematic review and meta-analysis of published observational evidence, to assess and quantify the associations of circulating OC (total, undercarboxylated, and carboxylated OC) with cardiovascular outcomes (clinical CVD endpoints and intermediate cardiovascular phenotypes).Design. Relevant studies were identified in a literature search of MEDLINE, EMBASE, and reference lists of relevant studies to March 2019. Mean differences and risk ratios with 95% CIs were aggregated using random-effects models.Results. Thirty-three observational studies (prospective and retrospective cohort, case-control, and cross-sectional) with data on 21,021 unique participants were eligible. The pooled risk ratio in a comparison of extreme fourths of total OC levels was 0.98 (95% CI 0.89, 1.08) for composite CVD. Circulating total OC levels were significantly lower in patients with cardiovascular conditions compared with those without these conditions -2.58 ng/ml (95% CI -3.85, -1.32; p < .001). Prospective and cross-sectional data showed significant inverse associations between total OC and traits such as aortic or coronary calcification, coronary atherosclerosis or calcification, carotid intima-media thickness, and plaque score. There was limited data on carboxylated and undercarboxylated OC, with no evidence of associations.Conclusion. Observational evidence generally supports inverse associations of circulating total OC with risk of atherosclerotic outcomes and CVD endpoints; however, the data were mostly based on cross-sectional evaluations. Large-scale prospective data are needed.


Identifying Child Anxiety Through Schools-identification to intervention (iCATS-i2i): protocol for single-arm feasibility trial.
Anxiety disorders are common among primary-school aged children, but few affected children receive evidence-based treatment. Identifying and supporting children who experience anxiety problems through schools would address substantial treatment access barriers that families and school staff often face. We have worked with families and school staff to co-design procedures that incorporate screening, feedback for parents, and the offer of a brief intervention in primary schools. This study sets out to assess the feasibility of a subsequent school-based cluster randomised controlled trial to evaluate these procedures. Our objectives are to ensure our procedures for identifying and supporting children with anxiety difficulties through primary schools are acceptable and there are no negative impacts, to estimate recruitment and retention rates, and to identify any changes needed to study procedures or measures. We will recruit six primary/junior schools in England (2 classes per school), and invite all children (aged 8-9) (n = 360) and their parent/carer and class teacher in participating classes to take part. Children, parents and class teachers will complete questionnaires at baseline and 12-week follow-up. Children who 'screen positive' on a 2-item parent-report child anxiety screen at baseline will be the target population (expected n = 43). Parents receive feedback on screening questionnaire responses, and where the child screens positive the family is offered support (OSI: Online Support and Intervention for child anxiety). OSI is a brief, parent-led online intervention, supported by short telephone sessions with a Children's Wellbeing Practitioner. Participants' experiences of study procedures will be assessed through qualitative interviews/discussion groups. Evidence-based procedures for identifying and supporting children with anxiety difficulties through primary schools would improve children's access to timely, effective intervention for anxiety difficulties. ISRCTN registry: ISRCTN30032471 . Retrospectively registered on 18 May 2021.


Biomechanical evaluation of finger trap suture variants for securing catheters.
To biomechanically evaluate various finger trap patterns and suture materials for securing 5F polyvinylchloride and polypropylene catheters. In vitro prospective study. 132 finger trap constructs. Each group of constructs comprised 6 to 10 replicates each of 3 finger trap patterns tied with 2-0 glycolide-lactide copolymer (GLC), braided nylon, and monofilament polypropylene suture on 5F polypropylene and polyvinylchloride catheters. The 3 finger trap variants were of similar lengths but differed in the number of surgeon's throws included in the pattern. Constructs were tested with a universal materials testing machine to the point of failure or a maximum of 100 mm of distraction. Force and distraction data were evaluated for significance with a competing risks model. There was no difference in performance (as measured by the proportion of test failures, median distraction distance, or median force at failure or end of testing) attributable to the finger trap pattern variants. Sixteen of 66 constructs with polyvinylchloride catheter material failed at ≤ 100 mm distraction, whereas all polypropylene constructs failed during testing. For polypropylene catheters, braided nylon or GLC suture withstood greater distraction distance and force, respectively. For polyvinylchloride catheters, differences among suture types were nonsignificant. Data suggested that, for the material combinations evaluated, a finger trap suture pattern with fewer knots may provide catheter security similar to that for patterns tied with a more traditional pattern. These results should not be extrapolated to catheters of different diameters or materials, patterns tied with different suture sizes, or clinical performance in vivo without further testing.


Vegetation greening in the Canadian Arctic related to decadal warming.
This study is presented within the context that climate warming and sea-ice decline has been occurring throughout much of the Arctic over the past several decades, and that terrestrial ecosystems at high latitudes are sensitive to the resultant alterations in surface temperatures. Results are from analyzing interannual satellite records of vegetation greenness across a bioclimate gradient of the Canadian Arctic over the period of 1982-2006. Here, we combine multi-scale sub-pixel analysis and remote sensing time-series analysis to investigate recent decadal changes in vegetation greenness along spatial gradients of summer temperature and vegetation. Linear autoregression temporal analysis of vegetation greenness was performed with relatively "pure" vegetation pixels of Advanced Very High Resolution Radiometer (AVHRR) data, spanning Low Arctic, High Arctic and polar desert ecosystems. Vegetation greenness generally increased over tundra ecosystems in the past two decades. Peak annual greenness increased 0.49-0.79%/yr over the High Arctic where prostrate dwarf shrubs, forbs, mosses and lichens dominate and 0.46-0.67%/yr over the Low Arctic where erect dwarf shrubs and graminoids dominate. However, magnitudes of vegetation greenness differ with length of time series and periods considered, indicating a nonlinear response of terrestrial ecosystems to climate change. The decadal increases of greenness reflect increasing vegetation production during the peak of the growing season, and were likely driven by the recent warming.


Concordant regulation of gene expression by hypoxia and 2-oxoglutarate-dependent dioxygenase inhibition: the role of HIF-1alpha, HIF-2alpha, and other pathways.
Studies of gene regulation by oxygen have revealed novel signal pathways that regulate the hypoxia-inducible factor (HIF) transcriptional system through post-translational hydroxylation of specific prolyl and asparaginyl residues in HIF-alpha subunits. These oxygen-sensitive modifications are catalyzed by members of the 2-oxoglutarate (2-OG) dioxygenase family (PHD1, PHD2, PHD3, and FIH-1), raising an important question regarding the extent of involvement of these and other enzymes of the same family in directing the global changes in gene expression that are induced by hypoxia. To address this, we compared patterns of gene expression induced by hypoxia and by a nonspecific 2-OG-dependent dioxygenase inhibitor, dimethyloxalylglycine (DMOG), among a set of 22,000 transcripts, by microarray analysis of MCF7 cells. By using short interfering RNA-based suppression of HIF-alpha subunits, we also compared responses that were dependent on, or independent of, the HIF system. Results revealed striking concordance between patterns of gene expression induced by hypoxia and by DMOG, indicating the central involvement of 2-OG-dependent dioxygenases in oxygen-regulated gene expression. Many of these responses were suppressed by short interfering RNAs directed against HIF-1alpha and HIF-2alpha, with HIF-1alpha suppression manifesting substantially greater effects than HIF-2alpha suppression, supporting the importance of HIF pathways. Nevertheless, the definition of genes regulated by both hypoxia and DMOG, but not HIF, distinguished other pathways most likely involving the action of 2-OG-dependent dioxygenases on non-HIF substrates.


Understanding Factors Influencing Dog Owners' Intention to Vaccinate Against Rabies Evaluated Using Health Belief Model Constructs.
Ethiopia has one of the highest incidence levels of human rabies in Africa, with 3-7 deaths per 100,000 people annually. The country has no official rabies control programme, despite the availability of an effective canine vaccine to control rabies. To support effective rabies control, an understanding of the factors affecting dog owners' voluntary intentions to vaccinate their dogs is important. As such, this study examined factors influencing dog owners' intentions to vaccinate their dogs using the constructs of health belief theory. In this cross-sectional study, a questionnaire, designed based on the Health Belief Model constructs was completed by 249 dog owners in 9 randomly selected wards of Bishoftu town in central Ethiopia between October and December 2016. An ordinal regression model was then fitted to explore factors which best predict the likelihood of a dog owner's intention. A classification and regression tree (CART) model was then used for recursive partitioning of the Likert scale in the significant variables to distinctively classify ordinal categories of vaccination intention. Participants' preventive intention was associated with the six constructs of the Health Belief Model: perceived susceptibility, readiness to action, self-efficacy, perceived threat, benefits, and barriers. Dog owner's knowledge about rabies was found to be positively associated with intention to vaccinate, whereas distance from vaccination centers and difficulty of dog transportation were found to be negatively associated to intention to vaccinate. Distance from vaccination center was found to be the best predictor for the intention to vaccinate. The results of this study have policy implications for controlling rabies including increasing dog owners' knowledge about rabies, locating vaccination centers at shorter distances from dog populations and providing suitable means to transport dogs to vaccination centers.


Comparison of ELISA and western blotting for human papillomavirus type 16 E7 antibody determination.
A total of 140 sera originating from healthy women and women with either cervical intraepithelial neoplasia or cervical cancer were tested for the presence of IgG antibody against E7 of human papillomavirus type 16 (HPV-16) by ELISA using a synthetic icosapeptide, denoted 16/E7-2, representing amino acids 11 to 30, and by Western blotting (WB) using a genetically engineered HPV-16 E7 fusion protein. Eighteen sera were found positive in either one or the other test. Positive reactions were more frequently detected in cervical carcinoma patients (12 of 34, 35.2%) than in the other individuals (six of 106, 5.7%). Ten children's (1 to 3 years of age) sera reacted in neither ELISA nor WB with HPV-16 E7. A high degree of concordance between the two tests was found suggesting that both tests detect the same or similar activity. To locate the reacting epitopes in the E7 protein, absorption tests were performed with peptides corresponding to various sections of the protein. Based on the results obtained, sera possessing antibody to HPV-16 E7 could be differentiated into those reactive with only the 16/E7-2 peptide and those reactive with other HPV-16 E7 epitopes.


Binding of neomycin-class aminoglycoside antibiotics to mutant ribosomes with alterations in the A site of 16S rRNA.
Aminoglycoside antibiotics that bind to the aminoacyl-tRNA site (A site) of the ribosome are composed of a common neamine core in which a glycopyranosyl ring is attached to position 4 of a 2-deoxystreptamine moiety. The core is further substituted by one (ribostamycin), two (neomycin and paromomycin), or three (lividomycin A) additional sugars attached to position 5 of the 2-deoxystreptamine. To study the role of rings III, IV, and V in aminoglycoside binding, we used isogenic Mycobacterium smegmatis DeltarrnB mutants carrying homogeneous populations of mutant ribosomes with alterations in the 16S rRNA A site. MICs were determined to investigate drug-ribosome interactions, and the results were compared with that of the previously published crystal structure of paromomycin bound to the ribosomal A site. Our analysis demonstrates that the stacking interaction between ring I and G1491 is largely sequence independent, that rings III and IV each increase the strength of drug binding to the ribosome, that ring IV of the 6'-NH3+ aminoglycosides compensates for loss of interactions between ring II and U1495 and between ring III and G1491, that the aminoglycosides rely on pseudo-base pairing between ring I and A1408 for binding independently of the number of sugar rings attached to the neamine core, that addition of ring V to the 6'-OH 4,5-aminoglycoside paromomycin does not alter the mode of binding, and that alteration of the U1406.U1495 wobble base pair to the Watson-Crick interaction pair 1406C-1495G yields ribosomal drug susceptibilities to 4,5-aminoglycosides comparable to those seen with the wild-type A site.


Candida albicans is able to use M cells as a portal of entry across the intestinal barrier in vitro.
Candida albicans is the most frequent yeast responsible for systemic infections in humans. These infections mainly originate from the gastrointestinal tract where C. albicans can invade the gut epithelial barrier to gain access to the bloodstream. Along the gut, pathogens can use Microfold (M) cells as a portal of entry to cross the epithelial barrier. M cells are specialized cells mainly located in the follicule-associated epithelium of Peyer patches. In this study, we used scanning electron and fluorescence microscopy, adhesion and invasion assays and fungal mutants to investigate the interactions of C. albicans with M cells obtained in an established in vitro model whereby enterocyte-like Caco-2 cells co-cultured with the Raji B cell line undergo a phenotypic switch to morphologically and functionally resembling M cells. Our data demonstrate that C. albicans co-localizes with and invades preferentially M cells, providing evidence that the fungus can use M cells as a portal of entry into the intestinal barrier. In addition to active penetration, F-actin dependent endocytosis contributes to internalization of the fungus into M cells through a mechanism involving hypha-associated invasins including Ssa1 and Als3.


The maternal age related patterns of infant low birth weight rates among non-Latino Whites and African-Americans: the effect of maternal birth weight and neighborhood income.
To determine the age related patterns of low birth weight (<2,500 g, LBW) and small for gestational age (weight <10th percentile for gestational age, SGA) among former LBW and non-LBW White and African-American mothers. We performed stratified analyses on an Illinois transgenerational dataset of non-Latina White (n = 31,616) and African-American (n = 38,964) infants born in Chicago or Suburban Cook County (1989-1991) and their mothers (1956-1976) with appended US census income information. In both races, LBW and SGA rates were unrelated to age among former LBW 14-35 year old mothers. LBW and SGA rates decreased with advancing age only among former non-LBW White mothers (p < 0.0001). Former non-LBW 30-35 year old White women (n = 11,096) had an infant LBW rate of only 4.3 % compared to 6.8 % for their teen counterparts (n = 1,383), RR (95 % CI) = 0.6 (0.5, 0.8). In contrast, a weathering pattern of rising LBW and SGA rates with advancing age occurred only among former non-LBW African-American mothers (p < 0.0001). Former non-LBW 30-35 year old African-American mothers (N = 4,807) had a LBW rate of 15.0 % compared to 10.8 % for their teen counterparts (N = 8,627), RR (95 % CI) = 1.4 (1.3, 1.5). The same trend occurred among the subgroup of African-American mothers with an early-life and adulthood residence in impoverished neighborhoods. Maternal low birth weight does not contribute to the disparate maternal age related patterns of adverse birth outcome between the races. Moreover, it is not associated with a weathering a pattern of rising rates of LBW with advancing age among African-American mothers with a lifelong residence in impoverished neighborhoods.


IL-17 Receptor A Maintains and Protects the Skin Barrier To Prevent Allergic Skin Inflammation.
Atopic dermatitis (AD) is a common inflammatory skin disease affecting up to 20% of children and 3% of adults worldwide and is associated with dysregulation of the skin barrier. Although type 2 responses are implicated in AD, emerging evidence indicates a potential role for the IL-17A signaling axis in AD pathogenesis. In this study we show that in the filaggrin mutant mouse model of spontaneous AD, IL-17RA deficiency (Il17ra-/- ) resulted in severe exacerbation of skin inflammation. Interestingly, Il17ra-/- mice without the filaggrin mutation also developed spontaneous progressive skin inflammation with eosinophilia, as well as increased levels of thymic stromal lymphopoietin (TSLP) and IL-5 in the skin. Il17ra-/- mice have a defective skin barrier with altered filaggrin expression. The barrier dysregulation and spontaneous skin inflammation in Il17ra-/- mice was dependent on TSLP, but not the other alarmins IL-25 and IL-33. The associated skin inflammation was mediated by IL-5-expressing pathogenic effector Th2 cells and was independent of TCRγδ T cells and IL-22. An absence of IL-17RA in nonhematopoietic cells, but not in the hematopoietic cells, was required for the development of spontaneous skin inflammation. Skin microbiome dysbiosis developed in the absence of IL-17RA, with antibiotic intervention resulting in significant amelioration of skin inflammation and reductions in skin-infiltrating pathogenic effector Th2 cells and TSLP. This study describes a previously unappreciated protective role for IL-17RA signaling in regulation of the skin barrier and maintenance of skin immune homeostasis.


Noninvasive bioluminescence imaging of α-synuclein oligomerization in mouse brain using split firefly luciferase reporters.
Alpha-synuclein (αSYN) aggregation plays a pivotal role in the pathogenesis of Parkinson's disease and other synucleinopathies. In this multistep process, oligomerization of αSYN monomers is the first step in the formation of fibrils and intracytoplasmic inclusions. Although αSYN oligomers are generally considered to be the culprit of these diseases, the methodology currently available to follow-up oligomerization in cells and in brain is inadequate. We developed a split firefly luciferase complementation system to visualize oligomerization of viral vector-encoded αSYN fusion proteins. αSYN oligomerization resulted in successful luciferase complementation in cell culture and in mouse brain. Oligomerization of αSYN was monitored noninvasively with bioluminescence imaging in the mouse striatum and substantia nigra up to 8 months after injection. Moreover, the visualized αSYN oligomers retained their toxic and aggregation properties in both model systems. Next, the effect of two small molecules, FK506 and (-)-epigallocatechin-3-gallate (EGCG), known to inhibit αSYN fibril formation, was investigated. FK506 inhibited the observed αSYN oligomerization both in cell culture and in mouse brain. In conclusion, the split firefly luciferase-αSYN complementation assay will increase our insight in the role of αSYN oligomers in synucleinopathies and opens new opportunities to evaluate potential αSYN-based neuroprotective therapies.


Strong optical injection and the differential gain in a quantum dash laser.
By optically injecting a quantum dash laser and simultaneously producing a significant lowering of the device threshold, a large enhancement in the differential gain is realized. This effect is observed by way of a dramatic reduction in the linewidth enhancement factor and a large increase in the 3-dB modulation bandwidth, especially as the injection wavelength is blue-shifted. Compared to its free-running value, a 50X improvement in the laser's differential gain is found.


Integrated Optics for Astronomical Interferometry. III. Optical Validation of a Planar Optics Two-Telescope Beam Combiner.
The optical characterization of a fiber-connected planar optics beam combiner dedicated to astronomical interferometry for two telescopes is presented. The beam combiner, fully integrated on a single 5 mm x 40 mm glass chip, is tested as the central part of an astronomical instrument. The single-mode waveguides are made by silver-ion-exchange technology upon glass substrates and provide spatial filtering, which improves the visibility measurement accuracy by selecting only the fundamental mode of the beams at the telescope focal plane. A global optical throughput of 43% is measured, and the sources of losses are identified and examined in detail. Solutions for improving this throughput are proposed. High and stable contrasts are obtained with a 1.55-mum laser diode (?96%) and with a white-light source (~92%) in the astronomical H filter (1.43 mum; 1.77 mum). The need for accurate control of differential instrumental polarization is demonstrated. In this context the intrinsic polarization-maintaining property of the planar optics component is characterized. This validation of the important potential uses of integrated planar optics should be valuable for future design of optical telescope arrays.


A one-pot synthesis of multifunctional Bi2S3 nanoparticles and the construction of core-shell Bi2S3@Ce6-CeO2 nanocomposites for NIR-triggered phototherapy.
As a direct thin band gap n-type semiconductor, bismuth sulfide (Bi2S3) nanomaterials possess great near-infrared (NIR)-triggered photothermal effects, photoacoustic (PA) and computed tomography (CT) imaging properties. Hence, Bi2S3 nanomaterials have become a research focal point in multiple domains, such as the construction of NIR-triggered nanosystems for cancer therapy. In this study, through a simple one-pot synthesis with the assistance of EDTA-2Na, we first obtained monodispersed spherical Bi2S3 of uniform particle sizes with fascinating photothermal and PA/CT imaging properties. Based on this, we introduced the photosensitizer Ce6 with photodynamic property and CeO2 with the O2-evolving characteristic, and thus designed a core-shell structure of the Bi2S3@Ce6-CeO2 nanocomposites (Bi2S3@Ce6-CeO2 NCs). The as-received Bi2S3@Ce6-CeO2 NCs exhibited a remarkable synergetic photothermal and photodynamic therapeutic effect both in vitro and in vivo, demonstrating its promising potential for cancer treatments. In the long term, the multifunctional PA/CT properties of both Bi2S3 NPs and Bi2S3@Ce6-CeO2 NCs in this study also supply a novel Bi2S3-based platform for constructing integrated diagnosis and treatment platforms.


Realization of integrated polarizer and color filters based on subwavelength metallic gratings using a hybrid numerical scheme.
This study realizes integrated polarizer and RGB (red, green, and blue) color filters using single- and multiple-layered subwavelength metallic grating structures. A hybrid numerical scheme based on the rigorous coupled-wave analysis method and a genetic algorithm is used to determine the optimal values of the grating period, filling factor, and grating thickness of three different grating structures, namely, a single-layer grating, a double-layer grating, and a double-layer grating with a lateral shift. The optical performance of the various structures is evaluated and compared in terms of the transmission efficiency at the center wavelengths 700.0 nm, 546.1 nm, and 435.8 nm of red, green, and blue light, respectively, and the extinction ratio over the visible wavelength spectrum (380-780 nm). It is shown that the double-layer grating achieves a transmission efficiency of about 50% and an extinction ratio of around 60 dB. Thus, this grating structure provides a convenient and effective means of achieving the polarizing and filtering functions in LCD panels using a single device.


Circadian clock genes contribute to the regulation of hair follicle cycling.
Hair follicles undergo recurrent cycling of controlled growth (anagen), regression (catagen), and relative quiescence (telogen) with a defined periodicity. Taking a genomics approach to study gene expression during synchronized mouse hair follicle cycling, we discovered that, in addition to circadian fluctuation, CLOCK-regulated genes are also modulated in phase with the hair growth cycle. During telogen and early anagen, circadian clock genes are prominently expressed in the secondary hair germ, which contains precursor cells for the growing follicle. Analysis of Clock and Bmal1 mutant mice reveals a delay in anagen progression, and the secondary hair germ cells show decreased levels of phosphorylated Rb and lack mitotic cells, suggesting that circadian clock genes regulate anagen progression via their effect on the cell cycle. Consistent with a block at the G1 phase of the cell cycle, we show a significant upregulation of p21 in Bmal1 mutant skin. While circadian clock mechanisms have been implicated in a variety of diurnal biological processes, our findings indicate that circadian clock genes may be utilized to modulate the progression of non-diurnal cyclic processes.


Early home intervention with low-birth-weight infants and their parents.
We investigated the effects of a year-long home intervention with a sample of preterm infants randomly assigned to 1 of 3 groups: a developmental intervention, a parent-infant intervention, and a no-treatment control group. A full-term no-treatment control was also used. Both intervention approaches focused on the parent-child unit, providing training for parents to improve observational skills, emotional support, and information about community resources. However, whereas specific tasks to facilitate the child's development were provided in the developmental intervention group, the quality of the parent-infant interaction was the target for treatment in the other group. All infants were assessed at 4, 8, 12, and 16 months of age corrected for prematurity. The results suggest that although both intervention approaches were effective in modifying some aspects of the home environment and, to a lesser degree, in improving infants' cognitive development, the parent-infant interaction approach seemed to have the greater impact. These findings confirm previous observations regarding the cognitive development of preterm and full-term infants during the first 18 months of life and demonstrate changes in behavior and behavior styles in both pre- and full-term infants as they become older.


Interaction of reduced lysozyme with surfactants: disulfide effects on reformed structure in micelles.
The reformation of secondary structure for unfolded, disulfide reduced hen egg white lysozyme (HEWL) upon interaction with surfactants was studied using CD, fluorescence and IR (infrared) techniques. Equilibrium CD studies showed that reduced HEWL when mixed with negatively charged surfactants, such as SDS (sodium dodecyl sulfate), gradually regains average helical structure to a level equivalent to that obtained for the oxidized form also in SDS, but both forms lose tertiary structure in such environments. This non-native structure recovery process begins with monomer surfactant interaction but at higher concentrations is in part dependent on micelle formation, with the helical fraction reaching its maximum value with each surfactant only above the CMC. Fluorescence changes were more complex, evidencing an intermediate state at lower surfactant concentration. With positively charged surfactants the degree of helicity recovered was less, and the intermediate state in fluorescence was not seen. Stopped flow dynamics studies showed the CD kinetics fit to two exponentials as did the fluorescence. The faster steps in CD and fluorescence detected kinetics appear to be correlated which suggests formation of an intermediate on rapid interaction of the micelle and protein. The second step then reflected attainment of a stable surfactant solvated state which attains maximum helicity and moves the Trps to a more hydrophobic environment, which may occur in independent steps, as the slower kinetics are not well correlated.


Dietary intake and barriers to dietary compliance in black type 2 diabetic patients attending primary health-care services.
To determine the dietary intake, practices, knowledge and barriers to dietary compliance of black South African type 2 diabetic patients attending primary health-care services in urban and rural areas. A cross-sectional survey. Dietary intake was assessed by three 24-hour recalls, and knowledge and practices by means of a structured questionnaire (n = 133 men, 155 women). In-depth interviews were then conducted with 25 of the patients to explore their underlying beliefs and feelings with respect to their disease. Trained interviewers measured weight, height and blood pressure. A fasting venous blood sample was collected from each participant in order to evaluate glycaemic control. An urban area (Sheshego) and rural areas near Pietersburg in the Northern Province of South Africa. The sample comprised 59 men and 75 women from urban areas and 74 men and 80 women from rural areas. All were over 40 years of age, diagnosed with type 2 diabetes for at least one year, and attended primary health-care services in the study area over a 3-month period in 1998. Reported dietary results indicate that mean energy intakes were low (< 70% of Recommended Dietary Allowance), 8086-8450 kJ day(-1) and 6967-7382 kJ day(-1) in men and women, respectively. Urban subjects had higher (P < 0.05) intakes of animal protein and lower ratios of polyunsaturated fat to saturated fat than rural subjects. The energy distribution of macronutrients was in line with the recommendations for a prudent diet, with fat intake less than 30%, saturated fat less than 10% and carbohydrate intake greater than 55% of total energy intake. In most respects, nutrient intakes resembled a traditional African diet, although fibre intake was low in terms of the recommended 3-6 g/1000 kJ. More than 90% of patients ate three meals a day, yet only 32-47% had a morning snack and 19-27% had a late evening snack. The majority of patients indicated that they followed a special diet, which had been given to them by a doctor or a nurse. Only 3.4-6.1% were treated by diet alone. Poor glycaemic control was found in both urban and rural participants, with more than half of subjects having fasting plasma glucose above 8 mmol l(-1) and more than 35% having plasma glycosylated haemoglobin level above 8.6%. High triglyceride levels were found in 24 to 25% of men and in 17 to 18% of women. Obesity (body mass index > or = 30 kg m(-2)) was prevalent in 15 to 16% of men compared with 35 to 47% of women; elevated blood pressure (> or = 160/95 mmHg) was least prevalent in rural women (25.9%) and most prevalent in urban men (42.4%). The majority of black, type 2 diabetic patients studied showed poor glycaemic control. Additionally, many had dyslipidaemia, were obese and/or had an elevated blood pressure. Quantitative and qualitative findings indicated that these patients frequently received incorrect and inappropriate dietary advice from health educators.