Associations of the objective built environment along the route to school with children's modes of commuting: A multilevel modelling analysis (the SLIC study).

As active commuting levels continue to decline among primary schoolchildren, evidence about which built environmental characteristics influence walking or cycling to school remains inconclusive and is strongly context-dependent. This study aimed to identify the objective built environmental drivers of, and barriers to, active commuting to school for a multi-ethnic sample of 1,889 healthy primary schoolchildren (aged 5-11) in London, UK. Using cross-sectional multilevel ordered logistic regression modelling, supported by the spatial exploration of built environmental characteristics through cartography, the objective built environment was shown to be strongly implicated in children's commuting behaviour. In line with earlier research, proximity to school emerged as the prime variable associated with the choice for active commuting. However, other elements of the urban form were also significantly associated with children's use of active or passive modes of transport. High levels of accidents, crime and air pollution along the route to school were independently correlated with a lower likelihood of children walking or cycling to school. Higher average and minimum walkability and higher average densities of convenience stores along the way were independently linked to higher odds of active commuting. The significance of the relations for crime, air pollution and walkability disappeared in the fully-adjusted model including all built environmental variables. In contrast, relationships with proximity, traffic danger and the food environment were maintained in this comprehensive model. Black children, pupils with obesity, younger participants and those from high socioeconomic families were less likely to actively commute to school. There is thus a particular need to ensure that roads with high volumes of actively commuting children are kept safe and clean, and children's exposure to unhealthy food options along the way is limited. Moreover, as short commuting distances are strongly correlated with walking or cycling, providing high-quality education near residential areas might incite active transport to school.

Associations of extracurricular physical activity patterns and body composition components in a multi-ethnic population of UK children (the Size and Lung Function in Children study): a multilevel modelling analysis.

BACKGROUND: Body Mass Index (BMI) is a common outcome when assessing associations between childhood overweight and obesity and physical activity patterns. However, the fat and fat-free components of BMI, measured by the Fat Mass Index (FMI) and Fat-Free Mass Index (FFMI), may show contrasting associations with physical activity, while ethnic groups may vary in both physical activity patterns and body composition. Body composition must therefore be evaluated when assessing the associations between childhood overweight and obesity and physical activity in multi-ethnic populations. METHODS: This cross-sectional study investigated associations of BMI, FMI and FFMI z-scores with extracurricular physical activity for 2171 London primary schoolchildren (aged 5-11 years) of black, South Asian and white/other ethnicity. Multilevel mixed-effects ordered logistic modelling was used, adjusting for age, sex and family and neighbourhood socioeconomic status as potential confounders. RESULTS: Controlling for ethnicity and individual, family and neighbourhood socioeconomic confounders, actively commuting children had significantly lower Odds Ratios for being in high BMI (Odds Ratio (OR) = 0.678; 95 % Confidence Interval (CI) = 0.531 - 0.865; p - value = 0.002) and FMI z-score groups (OR = 0.679; 95 % CI = 0.499 - 0.922; p = 0.013), but not FFMI z-score groups, than passive commuters. Children doing sports less than once a week had lower Odds Ratios for being in high BMI (OR = 0.435; 95 % CI = 0.236 - 0.802; p = 0.008) and FFMI (OR = 0.455; 95 % CI = 0.214 - 0.969; p = .041) z-score categories compared to daily active children. Differences in FMI between groups did not reach the significance threshold. A trend towards statistical significance was obtained whereby children's complete inactivity was associated with higher odds for being in higher BMI (OR = 2.222 : 95 % CI = 0.977 - 5.052; p = .057) and FMI z-score groups (OR = 2.485 : 95 % CI = 0.961 - 6.429; p = .060). FFMI z-scores did not show a similar trend with complete inactivity. CONCLUSIONS: Active commuting was objectively associated with lower adiposity, while more frequent extracurricular sports participation was correlated with greater fat-free mass accretion. These relationships were independent of ethnicity and individual, family or neighbourhood socioeconomic confounding factors.

Gut microbiota amplifies host-intrinsic conversion from the CD8 T cell lineage to CD4 T cells for induction of mucosal immune tolerance.

Microbiota has been shown to promote tolerogenic differentiation of T lymphocytes. It remains unclear to what extent microbiota triggers de novo re-programming or amplify pre-existing plasticity intrinsic to T cells. In a study with mouse models to track the clonal fate of CD4 and CD8 T cells, we discovered that CD8 T cells converted to MHC class I-restricted CD4 T cells without regard to selfness of their antigen specificity. In mesenteric lymph nodes (MLN), CD8 T cells converted to CD4(+)Foxp3(+) regulatory T (Treg) cells which were enriched in the large intestine lamina propria (LILP) and suppressed chemical- or immune-mediated inflammatory damage. In germ-free conditions, the converted CD4 populations were present in MLN, but absent in LILP. Therefore, an intrinsic plasticity in the host was amplified by the gut microbiota, leading to selfless tolerance induction in the intestinal mucosa. The findings may be relevant to HIV infection, cancer and autoimmune disorders.

The effects of freezing, boiling and degreasing on the microstructure of bone.

The histology of bone has been a useful tool in research. It is commonly used to estimate the age of an individual at death, to assess if the bone is of human or non-human origin and in trauma analysis. Factors that affect the histology of bone include age, sex, population affinity and burning to name but a few. Other factors expected to affect bone histology are freezing, boiling and degreasing but very little information is available for freezing and the effect thereof, and it is unknown if boiling and degreasing affects bone histology. The aim of this study was to assess the effects of freezing, freezing and boiling, and freezing, boiling and degreasing on the histological structure of compact bone. Five cadaver tibiae were frozen at -20°C for 21 days followed by segments being boiled in water for three days and degreased in trichloroethylene at 82°C for three days. Anterior midshaft sections were prepared as ground sections and for Scanning Electron Microscopy (SEM). Quantitatively, there were no significant differences between freezing, boiling and degreasing; however, qualitative differences were observed using SEM. After being frozen the bone displayed cracks and after boiling the bones displayed erosion pits on the surface. It is suggested that further research, using different durations and temperatures for boiling and freezing be undertaken on bone samples representing different ages and various skeletal elements.

Magnetic fields in superconducting neutron stars.

The interior of a neutron star is likely to be predominantly a mixture of superfluid neutrons and superconducting protons. This results in the quantization of the star's magnetic field into an array of thin flux tubes, producing a macroscopic force very different from the Lorentz force of normal matter. We show that in an axisymmetric superconducting equilibrium the behavior of a magnetic field is governed by a single differential equation. Solving this, we present the first self-consistent superconducting neutron star equilibria with poloidal and mixed poloidal-toroidal fields and also give the first quantitative results for the corresponding magnetically induced distortions to the star. The poloidal component is dominant in all our configurations. We suggest that the transition from normal to superconducting matter in a young neutron star may cause a large-scale field rearrangement.

A rapid and sensitive fluorometric method for the quantitative analysis of snake venom metalloproteases and their inhibitors.

Metalloproteases are responsible for the hemorrhagic effects of many snake venoms and contribute to other pathways that lead to local tissue damage. Methods that quantify snake venom metalloproteases (SVMP) are therefore valuable tools in research on the clinical, physiological, and biochemical effects of envenomation. Comparative analysis of individual, population, and species differences requires screening of large numbers of samples and treatments, and therefore require a method of quantifying SVMP activity that is simple, rapid, and sensitive. This paper demonstrates the properties of a new fluorometric assay of SVMP activity that can provide a measure of metalloprotease activity in 1 h. The assay is reliable, with variation among replicates sufficiently small to reliably detect differences in between species (F(19,60) = 2924, p < 0.001), even for those venoms with low overall activity. It is also sensitive enough to detect differences among venoms using <2 ng of whole venom protein. We provide an example use of this assay to detect the presence of natural SVMP inhibitors in minute samples of blood plasma from rock squirrels (S. variegatus), a natural prey species for North American rattlesnakes. We propose this assay is a useful addition to the set of tools used to characterize venoms, as well as high-throughput screening of natural or synthetic inhibitors, or other novel therapeutic agents against SVMP effects.

Dopamine D4 receptor and tyrosine hydroxylase genes in bipolar disorder: evidence for a role of DRD4.

The involvement of the mesocorticolimbic dopamine system in behaviors that are compromised in patients with mood disorder has led to the investigation of dopamine system genes as candidates for bipolar disorder. In particular, the functional VNTRs in the exon III of the dopamine D4 (DRD4) and in intron I of the tyrosine hydroxylase (TH) genes have been investigated in numerous association studies that have produced contrasting results. Likewise, linkage studies in multiplex bipolar families have shown both positive and negative results for markers in close proximity to DRD4 and TH on 11p15.5. We performed a linkage disequilibrium analysis of the DRD4 and TH VNTRs in a sample of 145 nuclear families comprised of DSM-IV bipolar probands and their biological parents. An excess of transmissions and non transmissions was observed for the DRD4 4- and 2-repeat alleles respectively. The biased transmission showed a parent of origin effect (POE) since it was derived almost exclusively from the maternal meiosis (4-repeat allele maternally transmitted 40 times vs 20 times non-transmitted; chi(2) = 6.667; df = 1; P = 0.009; while paternally transmitted 26 times vs 21 times non-transmitted; chi(2) = 0.531; df = 1; P = 0.46). The analysis of TH did not reveal biased transmission of intron I VNTR alleles. Although replication of our study is necessary, the fact that DRD4 exhibit POE and is located on 11p15.5, in close proximity to a cluster of imprinted genes, suggests that genomic imprinting may be operating in bipolar disorder.

Celecoxib for systemic lupus erythematosus: case series and literature review of the use of NSAIDs in SLE.

The primary objectives of this study were to evaluate the safety and efficacy of the cyclooxygenase-2 inhibitor celecoxib in systemic lupus erythematosus (SLE) patients both with and without a self-reported sulfa drug allergy and to review the literature on the use of nonsteroidal agents in SLE subjects. A retrospective review of medical records was performed for 50 SLE patients seen by a community-based rheumatologist and treated with open label celecoxib in doses of 200-400 mg/day for a period of 1-9 months. A MEDLINE search of all articles pertaining to the use of NSAIDs in patients with SLE since 1966 was undertaken. We noted that, in this cohort of celecoxib-treated SLE patients from an office rheumatology practice, the majority demonstrated some improvement, and little toxicity was observed. SLE patients with self-reported sulfa allergies were not more likely to have adverse reactions to celecoxib than non-sulfa allergic patients. The literature review performed herein reveals that, although NSAID toxicity should be a continuing concern in an SLE population, structural dissimilarities between celecoxib and the sulfonamide antimicrobials may make true cross-allergenicity less likely to be a clinical problem. These results suggest that patients with SLE can be safely and effectively treated with celecoxib; however, further studies are needed to assess the effectiveness and safety of all NSAIDs in SLE.

Prognostic awareness and the terminally ill.

The authors rated patients who were in advanced stages of cancer and in their final few weeks of life on their level of awareness of their medical prognosis (N = 200, mean age = 71.0 years). The authors measured prognostic awareness with a semistructured interview, dividing patients into those acknowledging No Awareness, Partial Awareness, and Complete Awareness. The authors also administered a semistructured interview for depressive disorders, along with an assessment of various demographic and social support measures. Nineteen patients (9.5%) denied awareness of both their terminal prognosis and foreshortened life expectancy. Thirty-four patients (17%) were placed in the partial awareness category, with the remaining 147 patients (73.5%) reporting complete awareness. Depression was nearly three times greater among patients who did not acknowledge their prognosis, as compared with those who demonstrated partial or complete acknowledgment (chi2 = 7.094), P = 0.029). In addition to depression, male patients, older patients, and those having "intense social contact" were associated with lower ratings of prognostic awareness. Dying patients differ in respect to their capacity to acknowledge their prognosis. Prognostic disavowal is most likely to arise in patients with underlying psychological distress and emotional turmoil.

Depression, Hopelessness, and suicidal ideation in the terminally ill.

This study investigated the mediational hypothesis of hopelessness in predicting suicidal ideation in a group of 196 patients with advanced terminal cancer. Each patient underwent a semistructured interview to assess hopelessness and suicidal ideation, and also completed the Beck Depression Inventory (short form). Hopelessness was correlated more highly with suicidal ideation than was the level of depression. In multiple linear-regression analyses, hopelessness contributed uniquely to the prediction of suicidal ideation when the level of depression was controlled. For health care providers attending to the needs of dying patients, hopelessness appears to be an important clinical marker of suicidal ideation in this vulnerable patient population.

A direct-interview family study of generalized social phobia.

OBJECTIVE: The goal of this direct-interview family study was to replicate and extend an earlier finding of a familial liability for social phobia. The authors hypothesized that there would be higher rates of the generalized type of social phobia--but not the nongeneralized (or "discrete") type--among relatives of probands with generalized social phobia. They also hypothesized that rates of avoidant personality disorder, a frequent comorbid condition, would be higher in relatives of probands with generalized social phobia. METHOD: The authors examined rates of three social phobia subtypes defined a priori--discrete, nongeneralized, and generalized--as well as rates of avoidant personality disorder by direct interview of 106 first-degree relatives of 23 patients with generalized social phobia and 74 first-degree relatives of 24 comparison subjects without social phobia. RESULTS: Relative risks for generalized social phobia and avoidant personality disorder were markedly higher (approximately 10-fold) among first-degree relatives of probands with generalized social phobia than among first-degree relatives of comparison probands. In contrast, relative risks for discrete social phobia and nongeneralized social phobia were not significantly different between the two groups of first-degree relatives. CONCLUSIONS: These results confirm earlier findings of a higher rate of social phobia among relatives of probands with generalized social phobia and extend these findings by specifically indicating that it is only the generalized type (and its probable axis II counterpart, avoidant personality disorder) that occurs more often among the families of probands with generalized social phobia. Implications for subsequent genetic studies are discussed.

"Are you depressed?" Screening for depression in the terminally ill.

OBJECTIVE: This study compared the performance of four brief screening measures for depression in a group of terminally ill patients. The methods included 1) a single-item interview assessing depressed mood, 2) a two-item interview assessing depressed mood and loss of interest in activities, 3) a visual analog scale for depressed mood, and 4) the Beck Depression Inventory-Short Form. METHOD: Semistructured diagnostic interviews for depression were administered to 197 patients receiving palliative care for advanced cancer. The interview diagnoses served as the standards against which the screening performance of the four brief screening methods was assessed. RESULTS: Single-item interview screening correctly identified the eventual diagnostic outcome of every patient, substantially outperforming the questionnaire and visual analog measures. CONCLUSIONS: Brief screening measures for depression are important clinical tools for terminally ill patients. For diagnostic purposes, however, they do not approach the validity of a single-item interview that asks, in effect, "Are you depressed?"

Intrainstitutional relocation. Effects on residents' behavior and psychosocial functioning.

INTRODUCTION: Relocation effects in the elderly have been a topic of gerontologic research for many years. Prior research, however, has focused on individuals who could make a cognitive appraisal of the relocation process. With a greater prevalence of cognitive impairments and/or psychiatric illnesses in long-term care residents, research is needed to clarify the impact of relocation on these individuals. OBJECTIVE: The purpose of this study was to determine how intrainstitutional relocation affects behavior and psychosocial functioning in residents with and without cognitive, mood, and/or psychotic disorders. METHOD: This prospective study followed 78 residents being relocated intrainstitutionally in a health-related facility that was undergoing major renovations. Medical and nursing information was collected at 1 month pre-move and at 1 and 3 months post-move. Five areas of behavioral and psychosocial functioning (self-care, disoriented behavior, depressed/anxious mood, irritable behavior, and withdrawn behavior) were assessed using the Multidimensional Observation Scale for Elderly Subjects (MOSES). RESULTS: A significant increase was seen in the number of medical visits (p = .04) from time of relocation to 1 month post-move. The groups diagnosed with mood disorder and psychotic disorder had a statistically significant weight loss (p = .04) between 1 month pre-move and 1 month post-move. The study revealed an increase in the number of residents who fell immediately after relocation, but the increase did not reach statistical significance (p = 12). Residents who fell after relocation had resided at the facility for a longer time than the remainder of the sample (p = .08). Residents with a diagnosis of cognitive impairment showed a statistically significant difference in self-care (p = 0.01) and withdrawn behavior (p = 0.01) at 3 months post-move. Extensive relocation preparation and support may have been the main contribution to diminishing the stress of relocation over time and across diagnostic categories.

Desire for death in the terminally ill.

OBJECTIVE: Euthanasia and physician-assisted suicide have become prominent medical and social issues. This study investigated the prevalence of the desire for death in terminally ill patients, the stability of this desire over time, and its association with psychiatric disorders. METHOD: Two hundred terminally ill inpatients were given semistructured interviews that assessed their desire for death and evaluated them for major and minor depressive episodes according to the Research Diagnostic Criteria. Each patient also completed a short form of the Beck Depression Inventory and provided ratings of pain and social support. When possible, patients who expressed a desire for death received a follow-up interview after a 2-week interval. RESULTS: Although occasional wishes that death would come soon were common (reported by 44.5% of the patients), only 17 (8.5%) of these individuals acknowledged a serious and pervasive desire to die. The desire for death was correlated with ratings of pain and low family support but most significantly with measures of depression. The prevalence of diagnosed depressive syndromes was 58.8% among patients with a desire to die and 7.7% among patients without such a desire. Follow-up interviews were conducted with six patients; in four cases, the desire to die had decreased during the 2-week interval. CONCLUSIONS: The desire for death in terminally ill patients is closely associated with clinical depression--a potentially treatable condition--and can also decrease over time. Informed debate about euthanasia should recognize the importance of psychiatric considerations, as well as the inherent transience of many patients' expressed desire to die.

Prevalence of depression in the terminally ill: effects of diagnostic criteria and symptom threshold judgments.

OBJECTIVE: Two issues that may influence the diagnosis of depression in the medically ill are 1) the severity with which symptoms must be expressed before they are considered clinically significant and 2) how to deal with somatic symptoms that may be caused by medical illness. This study used different approaches to case identification to examine prevalence rates for major and minor depression in a group of terminally ill cancer patients. METHODS: Semistructured diagnostic interviews were conducted with 130 patients receiving palliative care. Diagnoses according to the Research Diagnostic Criteria (RDC) were compared with diagnoses according to Endicott's revised criteria (which involve replacing somatic symptoms with non-somatic alternatives) when either a low-severity or a high-severity threshold for classifying RDC criterion A symptoms was used. RESULTS: A low-threshold (less stringent) diagnostic approach greatly increased the overall prevalence of major and minor depressive episodes with both the RDC and the Endicott criteria. With high thresholds, the RDC and the Endicott criteria were equivalent, whereas with low thresholds the Endicott substitutions identified fewer cases of major (but not minor) depression. CONCLUSIONS: Small differences between investigators in the applications of symptom-severity thresholds can result in large differences in prevalence rates for depression. However, the inclusions of somatic symptoms in the diagnostic criteria inflates the rates of diagnosis only when these symptoms are used in conjunction with a low-threshold approach.

Family psychoeducational support groups in schizophrenia.

Family members of 55 patients with schizophrenia were randomly assigned to a psychoeducational support group or to a control group. Support group participants showed greater knowledge of schizophrenia and greater satisfaction with health care services than did control group members. Psychological distress, coping behavior, and family satisfaction did not appear affected by support group participation; nor were support groups associated with lower rehospitalization rates for patients.

Structure of trans-3,3-dichloro-4-(alpha-chlorobenzyl)-1-methyl-5-phenyl-2-pyrrolidi none.

C18H16Cl3NO, Mr = 368.69, triclinic, P1-, a = 10.360 (1), b = 10.397 (1), c = 10.810 (2) A, alpha = 60.84 (1), beta = 57.22 (1), gamma = 70.97 (1) degrees, V = 852 (1) A3, Z = 2, Dx = 1.437 Mg m-3, Mo K alpha radiation, lambda = 0.71073 A, mu = 0.54 mm-1, F(000) = 380, T = 293 (1) K, R = 0.0287 for 2330 observed reflections with I greater than 3 sigma (I). The five-membered ring has an envelope conformation and the 4-(alpha-chlorobenzyl) and 5-phenyl groups are trans with respect to each other.

Toxoplasmosis: minimizing the risk of pet-associated transmission in persons with HIV disease.

Many misconceptions exist about the risks pets pose for the immunocompromised person. Home healthcare nurses, with their focus on health promotion and disease prevention, are in a primary position to disseminate accurate information to patients at risk.

Radioimmunotherapy of xenografts of human pancreatic carcinomas--intravenous and intratumoral application of 131I-labelled monoclonal antibodies.

The effects of radioimmunotherapy were tested in xenografts of 2 different human pancreatic carcinomas comparing the intravenous and intratumoral application. On principle, intravenous injections of high doses of 131I-anti-CA 19-9 or -BW 494/32 may inhibit tumor growth. In view of the low direct radiation dose (360-2100 rad), however, other factors than direct toxic effects have to be discussed, e.g. systemic effects due to the high whole-body irradiation. Intratumoral application, however, may induce tumor regression or growth inhibition due to the high local irradiation dose. Consequently, this treatment modality might be of clinical value at least in some patients.