The BeSMART (Best Supportive Management for Adults Referred with Tonsillopharyngitis) multicentre observational study.

Introduction Tonsillopharyngitis is the most common ear, nose and throat emergency admission, with 80,000 episodes recorded in England in 2015-2016. Despite this, there is a paucity of evidence addressing the supportive management of tonsillopharyngitis in inpatients. The aim of this retrospective multicentre observational study was to consider the Best Supportive Management for Adults Referred with Tonsillopharyngitis (BeSMART) in the inpatient setting, and to establish any associations between practice and outcomes. Methods Seven hospitals in North West England and North East Scotland participated in the study. Overall, 236 adult patients admitted with tonsillopharyngitis were included. The main outcome measures were interval to return to soft diet, length of stay (LOS), pain scores and readmissions. Results Women were more likely to seek professional help before presenting to secondary care (p=0.04). Patients admitted at the weekend were more likely to have a shorter LOS (p=0.03). There was no relationship between day of admission and seniority or specialty of the doctor initially seen. Prescription of corticosteroid, analgesia and a higher initial intravenous fluid infusion rate were not related to a shorter LOS. Conclusions This study is the first to yield valuable insights into the inpatient management of tonsillopharyngitis. This work represents part of an ongoing project to establish the evidence for common medical interventions for sore throat. Patient and professional surveys as well as a prospective interventional study are planned for the future.

Study protocol for a natural experiment in a lower socioeconomic area to examine the health-related effects of refurbishment to parks including built-shade (ShadePlus).

INTRODUCTION: Parks in disadvantaged suburbs often have low quality and few amenities, which is likely to result in them being underutilised for recreation and physical activity. Refurbishment of parks, including shade, walking paths and other amenities, may have broad health-related benefits. METHODS AND ANALYSIS: The study design, methods and planned analyses for a natural experiment examining the effects of refurbishments including built-shade added to parks in disadvantaged outer suburbs of Melbourne are described. Three intervention parks and three comparison parks matched for equivalence of park and neighbourhood characteristics were selected. Using mixed methods, the outcomes will be assessed during three consecutive spring-summer periods (T1: 2013-2014; T2: 2014-2015: T3: 2015-2016). Primary outcomes included: observed park use, physical activity and shade use. Self-reported social connectedness, community engagement and psychological well-being were assessed as secondary outcomes. ETHICS AND DISSEMINATION: This study was approved by Cancer Council Victoria's Human Research Ethics Committee. Studies such as ShadePlus can improve understanding of the broader effects of park refurbishments (including physical activity levels and sun protection behaviours, as well as social connectedness and psychological well-being). The study findings will be disseminated through established urban planning and parks and recreation networks, peer review publications and conference presentations.

What predicts children's active transport and independent mobility in disadvantaged neighborhoods?

This study examined two year changes in children's active transport and independent mobility and prospective associations between individual, social and physical environmental predictors of interest and these behaviors two years later. Overall, 43.5% of children (12.0±2.1 years) used active transport on the school journey at T1 and at T2 (p=0.77), and 35.3% engaged in independent mobility on the school journey at T1 and 29.6% at T2 (p=0.07). Enjoyment, parental safety concerns, and proximity to walking tracks were associated with independent mobility on the school journey. Road safety and social norms were associated with active transport and independent mobility to local destinations. These factors provide potential targets for interventions.

Objectively measured sedentary behaviour and health and development in children and adolescents: systematic review and meta-analysis.

Sedentary behaviour has emerged as a unique determinant of health in adults. Studies in children and adolescents have been less consistent. We reviewed the evidence to determine if the total volume and patterns (i.e. breaks and bouts) of objectively measured sedentary behaviour were associated with adverse health outcomes in young people, independent of moderate-intensity to vigorous-intensity physical activity. Four electronic databases (EMBASE MEDLINE, Ovid EMBASE, PubMed and Scopus) were searched (up to 12 November 2015) to retrieve studies among 2- to 18-year-olds, which used cross-sectional, longitudinal or experimental designs, and examined associations with health outcomes (adiposity, cardio-metabolic, fitness, respiratory, bone/musculoskeletal, psychosocial, cognition/academic achievement, gross motor development and other outcomes). Based on 88 eligible observational studies, level of evidence grading and quantitative meta-analyses indicated that there is limited available evidence that the total volume or patterns of sedentary behaviour are associated with health in children and adolescents when accounting for moderate-intensity to vigorous-intensity physical activity or focusing on studies with low risk of bias. Quality evidence from studies with robust designs and methods, objective measures of sitting, examining associations for various health outcomes, is needed to better understand if the overall volume or patterns of sedentary behaviour are independent determinants of health in children and adolescents.

What helps children to be more active and less sedentary? Perceptions of mothers living in disadvantaged neighbourhoods.

BACKGROUND: Increasing children's participation in physical activity and decreasing time spent in sedentary behaviours is of great importance to public health. Despite living in disadvantaged neighbourhoods, some children manage to engage in health-promoting physical activity and avoid high levels of screen-based activities (i.e. watching TV, computer use and playing electronic games). Understanding how these children manage to do well and whether there are unique features of their home or neighbourhood that explain their success is important for informing strategies targeting less active and more sedentary children. The aim of this qualitative study was to gain in-depth insights from mothers regarding their child's resilience to low physical activity and high screen-time. METHODS: Semi-structured face-to-face interviews were conducted with 38 mothers of children who lived in disadvantaged neighbourhoods in urban and rural areas of Victoria, Australia. The interviews were designed to gain in-depth insights about perceived individual, social and physical environmental factors influencing resilience to low physical activity and high screen-time. RESULTS: Themes relating to physical activity that emerged from the interviews included: parental encouragement, support and modelling; sports culture in a rural town; the physical home and neighbourhood environment; child's individual personality; and dog ownership. Themes relating to screen-time behaviours encompassed: parental control; and child's individual preferences. CONCLUSIONS: The results offer important insights into potential avenues for developing 'resilience' and increasing physical activity and reducing screen-time among children living in disadvantaged neighbourhoods. In light of the negative effects of low physical activity and high levels of screen-time on children's health, this evidence is urgently needed.

Risk factors for dissatisfaction with the indoor environment in open-plan offices: an analysis of COPE field study data.

UNLABELLED: We applied binary logistic regression techniques to data collected from 779 participants in a field study of open-plan ('cubicle') offices conducted in nine buildings. Independent variables were physical conditions in the workplace, and dependent variables were derived from occupant satisfaction measures; personal characteristics were included as covariates. There was a significantly higher risk of dissatisfaction with privacy and acoustics (defined as being below the 20th percentile as opposed to being above the 80th percentile) associated with being in a small workstation, or being seated next to a window. A higher risk of dissatisfaction with ventilation was associated with being seated next to a window, temperatures substantially higher than the average neutral temperature, and a carbon dioxide concentration greater than 650 ppm. A higher risk of dissatisfaction with lighting was associated with panel heights greater than 66 inches (1.7 m), high reflected glare on computer screens, desktop illuminances outside 300-500 lux, desktop illuminance uniformity (min/max ratio) less than 0.5, and being in a workstation distant from a window. PRACTICAL IMPLICATIONS: We have demonstrated statistically significant relationships between indoor environment conditions in office spaces and environmental dissatisfaction risk. Although generally supported by prior research, not all of these risk factors are reflected in existing recommended practice documents for office design. Consideration of these findings in future revisions of such documents may be warranted.

Children's active free play in local neighborhoods: a behavioral mapping study.

Many Australian children are more sedentary than they should be, and almost one in five are currently overweight or obese. Some children may face difficulties finding opportunities to be active, having poor access to safe public open spaces or having low independent mobility limiting their access to places to play. This study aimed to examine children's access to places in their neighborhood for active free play and how these vary by age, sex and socioeconomic status (SES). Behavioral maps of the local neighborhood were completed by children (8-12 years) from five primary schools across different areas of Melbourne. Children living in low SES outer-urban neighborhoods had to travel greater distances to access local parks compared with those in inner-urban mid and high SES areas. One-third (32%) of children reported an independent mobility range of <100 m from home. In conclusion, for some children opportunities to engage in active free play in the local neighborhood may be limited due to lack of parks in close proximity to home and restricted independent mobility. It is important to collaborate with local governments, urban planners and community groups to improve access to neighborhood parks and to promote a sense of neighborhood safety.

Patterns of Guillain-Barre syndrome in children: results from a Mexican population.

BACKGROUND: Guillain-Barré syndrome (GBS) is an acute, immune-mediated flaccid paralysis frequently associated with Campylobacter infection. Of two predominant GBS subtypes, a demyelinating subtype (acute inflammatory demyelinative polyneuropathy [AIDP]) predominates in the United States and Europe, and axonal subtype (acute motor axonal neuropathy [AMAN]) is the predominant form in China. Previous clinical studies suggested that AMAN also occurs in Mexican children. The purpose of this study was to describe the subtypes of GBS in children from Mexico City. METHODS: We prospectively studied 121 children admitted to two pediatric hospitals in Mexico City from 1996 to 2002. Clinical histories were obtained, electrophysiologic studies were performed to determine GBS subtype, and microbiologic studies were performed. RESULTS: Of the 121 children, 46 had AMAN and 32 had AIDP. The male to female ratio was 1.3 for AMAN cases (mean age = 6.3) and 3.0 for AIDP cases (mean age = 7.0). There was a strong seasonal distribution of AMAN cases in July to September. Children with AMAN, but not AIDP, had worsening of illness during hospitalization as judged by peak severity scores. Vomiting was more likely in AIDP (28.1%) vs AMAN (6.5%) (p = 0.012) and diarrhea was more common in AMAN (32.6%) than AIDP (12.5%) (p = 0.06). IgG anti-GM1 antibody titers were higher in patients with AMAN vs AIDP (p = 0.067). Anti-GD1a antibodies were equally present in both groups. Anti GQ1b titers were higher in AMAN vs AIDP (p = 0.009). Campylobacter antibody responses were positive in 44.1% of patients with AMAN and 37.0% of patients with AIDP. Twenty patients (14 = AMAN, 6 = AIDP) had positive stool cultures for C jejuni. Two serotypes, HS:19 and HS:41, accounted for 6 of 10 Campylobacter isolates available for serotyping from these cases. CONCLUSIONS: This study confirms that acute motor axonal neuropathy is an important Guillain-Barré syndrome subtype in Mexican children, is associated with diarrhea, and occurs seasonally.

The clinical and laboratory features of chronic sensory ataxic neuropathy with anti-disialosyl IgM antibodies.

The clinical and laboratory phenotype of a paraproteinaemic neuropathy syndrome termed chronic sensory ataxic neuropathy with anti-disialosyl IgM antibodies is described in a series of 18 cases. Previous single case reports have outlined some features of this syndrome. All 18 cases were defined by the presence of serum IgM antibodies which react principally with NeuAc (alpha2-8)NeuAc(alpha2-3)Gal-configured disialosyl epitopes common to many gangliosides including GDlb, GD3, GTlb and GQlb. In 17 out of 18 cases, the serum contained benign IgM paraproteins, and in four of these cases at least two IgM paraproteins were present. The IgM antibodies were also cold agglutinins in 50% of cases. The clinical picture comprised a chronic neuropathy with marked sensory ataxia and areflexia, and with relatively preserved motor function in the limbs. In addition, 16 out of 18 cases had motor weakness affecting oculomotor and bulbar muscles as fixed or as relapsing-remitting features. When present in their entirety, these clinical features have been described previously under the acronym CANOMAD: chronic ataxic neuropathy, ophthalmoplegia, IgM paraprotein, cold agglutinins and disialosyl antibodies. This distribution of clinical features is reminiscent of Miller Fisher syndrome, in which acute-phase anti-disialylated ganglioside IgG antibodies are found. Clinical electrophysiology and nerve biopsy show both demyelinating and axonal features. A partial response to intravenous immunoglobulin and other treatments is reported in some cases.

Full-spectrum fluorescent lighting: a review of its effects on physiology and health.

BACKGROUND: Full-spectrum fluorescent lighting (FSFL) has been credited with causing dramatic beneficial effects on a wide variety of behaviours, mental health outcomes and physical health effects, as compared to other fluorescent lamp types. These effects are hypothesized to occur because of similarity between FSFL emissions and daylight, which is said to have evolutionary superiority over other light sources. METHOD: This review, covering the period 1941-1999, critically considers the evidence for direct effects of FSFL through skin absorption as well as indirect effects on hormonal and neural processes. CONCLUSIONS: Overall, the evidence does not show dramatic effects of fluorescent lamp type on behaviour or health, neither does it support the evolutionary hypothesis.

Production, isolation and structure determination of novel fluoroindolocarbazoles from Saccharothrix aerocolonigenes ATCC 39243.

Saccharothrix aerocolonigenes ATCC 39243 produces an indolocarbazole antitumor agent rebeccamycin under submerged fermentation conditions. Adding DL-6-fluorotryptophan to culture of S. aerocolonigenes ATCC 39243 induces the formation of two novel indolocarbazoles, fluoroindolocarbazoles A and B. Feeding DL-5-fluorotryptophan to culture of S. aerocolonigenes ATCC 39243 induces the production of a novel indolocarbazole, fluoroindolocarbazole C. These fluoroindolocarbazoles have been isolated from culture broth and purified to homogeneity by vacuum liquid chromatography and column chromatography. All three fluoroindolocarbazoles are more potent than rebeccamycin against P388 leukemia by ip route in murine model.

A critical examination of perceptual and cognitive effects attributed to full-spectrum fluorescent lighting.

Full-spectrum fluorescent lighting (FSFL) has been credited with causing dramatic improvements in vision, perception and cognitive performance as compared with other fluorescent lamp types. These effects are hypothesized to occur because of similarity between FSFL emissions and daylight, which is said to have evolutionary superiority over other light sources. This review, covering 1945-98, critically considers the evidence for these claims. In general, poor-quality research has resulted in an absence of simple deterministic effects that can be confidently attributed to fluorescent lamp type. Promising avenues for lighting behaviour research include investigations of cognitive mediators of lighting-behaviour relationships, and flicker rates and colour rendering effects on visual processing, appearance judgements and affect. Good lighting solutions are more complex than lamp type specification.

Peripheral neuropathy associated with anti-GM2 ganglioside antibodies: clinical and immunopathological studies.

GM2 ganglioside is a potential peripheral nerve antigen for neuropathy-associated autoantibodies. However little data are available on their pathogenic effects, if any. In this study we have screened both neuropathy-associated and control sera for anti-GM2 antibodies and subsequently used high titre sera for immunohistological and complement mediated cytotoxicity studies. We identified abnormally elevated anti-GM2 antisera in the normal population, as well as in patients with peripheral neuropathies and other neurological diseases. GM2 antibodies were either mono-reactive, cross-reactive with GM1a, or cross-reactive with GalNAc-GM1b and/or GalNAc-GD1a. All GM2 antisera from neuropathy subjects and normal controls bound to, and were capable of complement-mediated lysis of the NSC-34 cell line which expresses high levels of membrane-associated GM2. However, in immunohistological studies on human and rodent peripheral nervous system tissues, no specific binding was seen with GM2 antisera, either cross-reactive with GalNAc-GM1b and GalNAc-GDla, or with GM1a. These data indicate that although GM2 antisera can lyse neural membranes containing GM2, this antigen(s) is not detectable by standard immunohistological techniques in human or rodent peripheral nerve. This raises doubts about their pathophysiological significance in human autoimmune neuropathy.

Long-term clinical and neurophysiological follow-up of patients with peripheral, neuropathy associated with benign monoclonal gammopathy.

The incidence of hematological malignancy in patients with monoclonal gammopathy of undetermined significance (MGUS) has been assessed as 17% to 25%. To ascertain whether this is true of neuropathy associated with MGUS, a long-term (5-42 years) retrospective clinical and neurophysiological follow-up was conducted in 50 cases (immunoglobulin M [IgM], n = 38; IgG, n = 11; IgA, n = 1). Only three patients developed hematological malignancy. Of 25 survivors with IgM paraproteinemia, 7 had myelin-associated glycoprotein antibodies with typical clinical features. Evoked distal muscle amplitudes were significantly smaller than for the other paraprotein classes. Preferential distal demyelination manifested by relative prolongation of distal motor latency was not apparent in the cases of long duration. Two patients with IgM antidisialosyl antibodies and cold agglutinating activity had a large fiber neuropathy with intermittent oculofacial involvement. Both responded to intravenous immunoglobulin. Findings in the remaining patients were varied. Recognition of IgM subgroups is important both for prognosis and possible response to treatment.

A centralized global automation group in a decentralized organization.

In the latter part of the 1990s, many companies have worked to foster a 'matrix' style culture through several changes in organizational structure. This type of culture facilitates communication and development of new technology across organizational and global boundaries. At Glaxo Wellcome, this matrix culture is reflected in an automation strategy that relies on both centralized and decentralized resources. The Group Development Operations Information Systems Robotics Team is a centralized resource providing development, support, integration, and training in laboratory automation across businesses in the Development organization. The matrix culture still presents challenges with respect to communication and managing the development of technology. A current challenge for our team is to go beyond our recognized role as a technology resource and actually to influence automation strategies across the global Development organization. We shall provide an overview of our role as a centralized resource, our team strategy, examples of current and past successes and failures, and future directions.

Physical activity initiatives for male factory workers: gatekeepers' perceptions of potential motivators and barriers.

OBJECTIVE: Worksites have been argued to be a key setting for physical activity promotion, particularly for lower-paid, less-skilled workers. These occupational groups are at increased risk of cardiovascular disease. There is no strong evidence in support of the efficacy of worksite fitness and physical activity interventions. This study assessed potential motivators and barriers to worksite physical activity initiatives for less-skilled workers. METHOD: We conducted telephone interviews with 13 Victorian WorkCover insurance providers and 30 manufacturing industry worksite managers. The manufacturing industry was selected as it contains a substantial portion of workers from this high-risk occupational group. RESULTS: Most insurers incorporated physical activity elements into injury-prevention programs. Few worksite managers reported programs to encourage workers to be more active; they identified reduced premiums and lower-cost programs through insurers as possible motivators. Both groups identified workers' reluctance to participate in physical activity, lack of awareness of potential benefits and program cost as major barriers for worksite physical activity. Other barriers included potential adverse effects on productivity and increased injury risk. CONCLUSIONS: Broader occupational health and safety policies and joint initiatives between insurers and worksite managers may have the potential to provide more opportunities for workers to be more active. However, the barriers identified outweighed the perceived benefits. IMPLICATIONS: Without structural and regulatory changes or new incentives, the adoption of physical activity initiatives in Australian manufacturing-industry workplaces is unlikely.

Physical inactivity and other health risks among Australian males in less-skilled occupations.

Male workers in less-skilled occupations have higher rates of cardiovascular disease, compared with higher-skilled workers. A representative population sample of Australian male workers was used to compare physical activity levels and selected cardiovascular disease risk factors in less-skilled versus professional and skilled workers. Workers in the less-skilled occupational categories reported significantly more vigorous work and home-based activity than did those in the professional and skilled categories. In multivariate comparisons, cigarette smoking was the only factor that discriminated between the less-skilled versus the professional and skilled employees. Although worksites can potentially provide health-promoting physical activity options for higher-risk groups, our findings suggest that smoking and possibly overweight are risk factors that are more strongly present in less-skilled occupations.

Monoclonal antibodies raised against Guillain-Barré syndrome-associated Campylobacter jejuni lipopolysaccharides react with neuronal gangliosides and paralyze muscle-nerve preparations.

Guillain-Barré syndrome and its variant, Miller-Fisher syndrome, are acute, postinfectious, autoimmune neuropathies that frequently follow Campylobacter jejuni enteritis. The pathogenesis is believed to involve molecular mimicry between sialylated epitopes on C. jejuni LPSs and neural gangliosides. More than 90% of Miller-Fisher syndrome cases have serum anti-GQ1b and anti-GT1a ganglioside antibodies that may also react with other disialylated gangliosides including GD3 and GD1b. Structural studies on LPS from neuropathy-associated C. jejuni strains have revealed GT1a-like and GD3-like core oligosaccharides. To determine whether this structural mimicry results in pathogenic autoantibodies, we immunized mice with GT1a/GD3-like C. jejuni LPS and then cloned mAb's that reacted with both the immunizing LPS and GQ1b/GT1a/GD3 gangliosides. Immunohistology demonstrated antibody binding to ganglioside-rich sites including motor nerve terminals. In ex vivo electrophysiological studies of nerve terminal function, application of antibodies either ex vivo or in vivo via passive immunization induced massive quantal release of acetylcholine, followed by neurotransmission block. This effect was complement-dependent and associated with extensive deposits of IgM and C3c at nerve terminals. These data provide strong support for the molecular mimicry hypothesis as a mechanism for the induction of cross-reactive pathogenic anti-ganglioside/LPS antibodies in postinfectious neuropathies.

Glucolipsin A and B, two new glucokinase activators produced by Streptomyces purpurogeniscleroticus and Nocardia vaccinii.

During the screening of the natural products for their ability to increase the activity of glucokinase by relieving inhibition by long chain fatty acyl CoA esters (FAC), two novel compounds, glucolipsin A (1) and B (2) were isolated from the butanol extracts of Streptomyces purpurogeniscleroticus WC71634 and Nocardia vaccinii WC65712, respectively. The structures of these two compounds were established by spectroscopic methods and chemical degradation. Glucolipsin A (1) and B (2) relieved the inhibition of glucokinase by FAC with RC50 values of 5.4 and 4.6 microM.

Inter-laboratory validation of an ELISA for the determination of serum anti-ganglioside antibodies.

Anti-ganglioside antibodies are frequently sought in the sera of patients with autoimmune peripheral neuropathy, using an enzyme-linked immunosorbent assay (ELISA) as the principal method for antibody detection. Wide variations in assay performance between laboratories have been reported. In this study, we established a standardized ELISA method between laboratories within the European Inflammatory Neuropathy Cause and Treatment (INCAT) group and determined the inter-laboratory variance in assay performance using both the standardized INCAT method and in-house local methods. As expected, the inter-laboratory variances were greater using local methods than using the standardized method, producing titre estimates which could be 24.8 or 7.6 times larger or smaller, respectively, than the true means for these laboratories. Using the standardized method, the within laboratory measurement error accounted for 41% of the inter-laboratory variation, providing a theoretical upper limit to which technical improvements within laboratories could reduce inter-laboratory variation. These data describe the intrinsic weaknesses within the widely used ganglioside antibody ELISA methods and reinforce the importance of inter-laboratory cooperation within this area. Standardized serological reagents used in this study are available from INCAT members.