Influence of ventilation use and occupant behaviour on surface microorganisms in contemporary social housing.

In the context of increasingly airtight homes, there is currently little known about the type and diversity of microorganisms in the home, or factors that could affect their abundance, diversity and nature. In this study, we examined the type and prevalence of cultivable microorganisms at eight different sites in 100 homes of older adults located in Glasgow, Scotland. The microbiological sampling was undertaken alongside a household survey that collated information on household demographics, occupant behaviour, building characteristics, antibiotic use and general health information. Each of the sampled sites revealed its own distinct microbiological character, in both species and number of cultivable microbes. While some potential human pathogens were identified, none were found to be multidrug resistant. We examined whether the variability in bacterial communities could be attributed to differences in building characteristics, occupant behaviour or household factors. Sampled sites furnished specific microbiological characteristics which reflected room function and touch frequency. We found that homes that reported opening windows more often were strongly associated with lower numbers of Gram-negative organisms at indoor sites (p < 0.0001). This work offers one of the first detailed analysis of cultivable microbes in homes of older adults and their relationship with building and occupancy related factors, in a UK context.

Amplifying the Voice of the Patient in Clinical Research: Development of Toolkits for Use in Designing and Conducting Patient-Centered Clinical Studies.

Incorporating patient perspectives into clinical studies is recognized as important to the development of high-quality, safe, and effective fit-for-patient medicines. However, no widely accepted methodology to help design more patient-centered studies has been established systematically. TransCelerate Biopharma Inc., a non-profit organization promoting collaboration across biopharmaceutical companies, organized a Patient Experience (PE) Initiative to create tools to intentionally include the patient perspective into the design and implementation of clinical studies. The resulting tools include the Patient Protocol Engagement Toolkit (P-PET), to engage patients early in protocol development, and the Study Participant Feedback Questionnaire (SPFQ), to assess patient experiences during clinical studies. To develop these toolkits, TransCelerate conducted a literature review and identified aspects of clinical studies that patients find either valuable or burdensome, or that affect participation, adherence, and engagement in a clinical study. The concepts identified were refined through elicitation of feedback from patient advisors, clinical study site advisors, and subject matter experts from member companies (MCs) of TransCelerate. This feedback was considered in identifying gaps, defining scientific methodology to understand how to evaluate patients' needs, and developing and refining the P-PET and the SPFQ. As part of the development process, descriptions/drafts of the tools were shared with patients, clinical site advisory groups, MCs, and the US Food and Drug Administration, and then revised. MCs simulated use of the tools, and feedback was incorporated into the final versions of the P-PET and SPFQ prior to public release. The P-PET and SPFQ are available free on the TransCelerate website.

Use of the UKHCDO Database for a postmarketing surveillance study of different doses of recombinant factor VIIa in haemophilia.

INTRODUCTION: Recombinant factor VIIa (rFVIIa) is recommended in Europe at standard (3 × 90 µg kg-1 ) or high (1 × 270 µg kg-1 ) doses. When granting the license for the high dose, the European Medicines Agency (EMA) requested postmarketing surveillance for thrombosis. This was conducted by the United Kingdom National Haemophilia Database (NHD) on behalf of Novo Nordisk and the EMA. AIM: To assess the use and safety of rFVIIa utilizing prospective data collected by the NHD (1 January 2008 to 30 June 2011). RESULTS: Data were obtained from 67 haemophilia A/B patients with inhibitors treated for 1057 bleeds and 31 acquired haemophilia patients treated for 70 bleeds. Initial rFVIIa dose was categorized post hoc as low (<90 µg kg-1 ), intermediate (≥90-<180 µg kg-1 ) or high (≥180-<270 or ≥270 µg kg-1 ). For haemophilia A/B, high and lower initial rFVIIa dose was used for 38.4% and 51.4% of episodes, respectively, while for acquired haemophilia, the values were 11.4% and 77.1% respectively. Median initial doses were higher for haemophilia A/B (146.3 µg kg-1 ) than acquired haemophilia (90.5 µg kg-1 ). A single administration of rFVIIa was the most frequently used regimen for haemophilia A/B, in contrast with standard recommendations and previous reports. For acquired haemophilia, most episodes were treated with multiple doses. No adverse drug reactions or thromboembolic events were reported for any rFVIIa dose. CONCLUSION: The novel use of a national database for postmarketing surveillance has demonstrated acceptable safety for all recommended doses of rFVIIa.

Prevalence, demographic variation and psychological correlates of exposure to police victimisation in four US cities.

Aims Victimisation by the police is purported to be widespread in cities in the USA, but there is limited data on police-public encounters from community samples. This is partly due to an absence of measures for assessing police violence exposure from the standpoint of civilians. As such, the demographic distribution and mental health correlates of police victimisation are poorly understood. The aims of this study were to present community-based prevalence estimates of positive policing and police victimisation based on assessment with two novel measures, and to test the hypotheses that (1) exposure to police victimisation would vary across demographic groups and (2) would be associated with depression and psychological distress. METHODS: The Survey of Police-Public Encounters study surveyed adults residing in four US cities to examine the prevalence, demographic distribution and psychological correlates of police victimisation. Participants (N = 1615) completed measures of psychological distress (K-6 scale), depression (Patient Health Questionnaire 9) and two newly constructed measures of civilian-reported police-public encounters. Both measures were developed to assess police victimisation based on the WHO domains of violence, which include physical violence (with and without a weapon, assessed separately), sexual violence (inappropriate sexual contact, including public strip searches), psychological violence (e.g., threatening, intimidating, stopping without cause, or using discriminatory slurs) and neglect (police not responding when called or responding too late). The Police Practices Inventory assesses lifetime history of exposure to positive policing and police victimisation, and the Expectations of Police Practices Scale assesses the perceived likelihood of future incidents of police victimisation. Linear regression models were used to test for associations between police-public encounters and psychological distress and depression. RESULTS: Psychological violence (18.6%) and police neglect (18.8%) were commonly reported in this sample and a substantial minority of respondents also reported more severe forms of violence, specifically physical (6.1%), sexual (2.8%) and physical with a weapon (3.3%). Police victimisation was more frequently reported by racial/ethnic minorities, males, transgender respondents and younger adults. Nearly all forms of victimisation (but not positive policing) were associated with psychological distress and depression in adjusted linear regression models. CONCLUSIONS: Victimisation by police appears to be widespread, inequitably distributed across demographic groups and psychologically impactful. These findings suggest that public health efforts to both reduce the prevalence of police violence and to alleviate its psychological impact may be needed, particularly in disadvantaged urban communities.

Effect of flip-flops on lower limb kinematics during walking: a cross-sectional study using three-dimensional gait analysis.

BACKGROUND: Flip-flops are a popular footwear choice in warm weather however their minimalist design offers little support to the foot. AIM: To investigate the effect of flip-flops on lower limb gait kinematics in healthy adults, to measure adherence between the flip-flop and foot, and to assess the effect on toe clearance in swing. METHODS: Fifteen healthy adults (8 male, mean age 27 years) completed a three-dimensional gait analysis assessment using Codamotion. Kinematic and lower limb temporal-spatial data were captured using the Modified Helen Hayes marker set with additional markers on the hallux and flip-flop sole. RESULTS: Compared to barefoot walking, there were no differences in temporal-spatial parameters walking with flip-flops. There was an increase in peak knee flexion in swing (mean difference 4.6°, 95 % confidence interval (CI) [-5.8°, -3.4°], p < 0.001) and peak ankle dorsiflexion at terminal swing (mean difference 2°, 95 % CI [-3°, -1°], p = 0.001). Other kinematic parameters were unchanged. Peak separation between foot and flip-flop was 8.8 cm (SD 1.48), occurring at pre-swing. Minimum toe clearance of the hallux in barefoot walking measured 4.2 cm (SD 0.8). Minimum clearance of the flip-flop was 1.6 cm (SD 0.56). CONCLUSIONS: Healthy adults adapted well to flip-flops. However, separation of the flip-flop from the foot led to increased knee flexion and ankle dorsiflexion in swing, probably to ensure that the flip-flop did not contact the ground and to maximise adherence to the foot. Minimum clearance of the flip-flop was low compared to barefoot clearance. This may increase the risk of tripping over uneven ground.

Disinfectant wipes are appropriate to control microbial bioburden from surfaces: use of a new ASTM standard test protocol to demonstrate efficacy.

BACKGROUND: The use of disinfectant pre-soaked wipes (DPW) to decontaminate high-touch environmental surfaces (HTES) by wiping is becoming increasingly widespread in the healthcare environment. However, DPW are rarely tested using conditions simulating their field use, and the label claims of environmental surface disinfectants seldom include wiping action. AIM: To evaluate the new E2967-15 standard test specific to wipes, particularly their ability to decontaminate surfaces and to transfer acquired contamination to clean surfaces. METHODS: ASTM Standard E2967-15 was used by three independent laboratories to test the efficacy of five types of commercially available wipe products. All data generated were pulled together, and reproducibility and repeatability of the standard were measured. FINDINGS: All the commercial DPW tested achieved a >4log10 (>99.99%) reduction in colony-forming units (CFU) of Staphylococcus aureus and Acinetobacter baumanii with 10s of wiping, but only one DPW containing 0.5% accelerated H2O2 prevented the transfer of bacteria to another surface. CONCLUSION: This newly introduced standard method represents a significant advance in assessing DPW for microbial decontamination of HTES, and should greatly assist research and development, and in making more relevant and reliable claims on marketed DPW.

Injuries associated with traumatic anterior glenohumeral dislocations.

BACKGROUND: A number of shoulder girdle injuries are associated with acute anterior glenohumeral dislocations. In the present study we evaluated the prevalence of neurological deficits, greater tuberosity fractures, and rotator cuff injuries in a population of unselected patients who presented with a traumatic anterior glenohumeral dislocation. METHODS: A prospective trauma database was used to record the demographic details on 3633 consecutive patients (2250 male patients and 1383 female patients with a mean age of 47.6 years) who had sustained a traumatic anterior glenohumeral dislocation between 1995 and 2009. On the basis of these data, we assessed the prevalence of and risk factors for ultrasound-proven rotator cuff tears, tuberosity fractures, and neurological deficits occurring in association with the dislocation. RESULTS: Of the 3633 patients who had a dislocation, 492 patients (13.5%) had a neurological deficit following reduction and 1215 patients (33.4%) had either a rotator cuff tear or a greater tuberosity fracture. A dislocation with a neurological deficit alone was found in 210 patients (5.8%), a dislocation with a rotator cuff tear or a greater tuberosity fracture was found in 933 patients (25.7%), and a combined injury pattern was found in 282 patients (7.8%). Female patients with an age of sixty years or older who were injured in low-energy falls were more likely to have a rotator cuff tear or a greater tuberosity fracture. The likelihood of a neurological deficit after an anterior glenohumeral dislocation was significantly increased for patients who had a rotator cuff tear or a greater tuberosity fracture (relative risk, 1.9 [95% confidence interval, 1.7 to 2.1]; p < 0.001). CONCLUSIONS: The prevalence of rotator cuff tear, greater tuberosity fracture, or neurological deficit following primary anterior glenohumeral dislocation is greater than previously appreciated. These associated injuries may occur alone or in combined patterns. Dislocations associated with axillary nerve palsy have similar demographic features to isolated dislocations. Injuries associated with a rotator cuff tear, greater tuberosity fracture, or complex neurological deficit are more common in patients sixty years of age or older. Careful evaluation of rotator cuff function is required for any patient with a dislocation associated with a neurological deficit, and vice versa.

Open reduction and endobutton fixation of displaced fractures of the lateral end of the clavicle in younger patients.

Displaced fractures of the lateral end of the clavicle in young patients have a high incidence of nonunion and a poor functional outcome after conservative management. Operative treatment is therefore usually recommended. However, current techniques may be associated with complications which require removal of the fixation device. We have evaluated the functional and radiological outcomes using a novel technique of open reduction and internal fixation. A series of 16 patients under 60 years of age with displaced fractures of the lateral end were treated by open reduction and fixation using a twin coracoclavicular endobutton technique. They were followed up for the first year after their injury. At one year the mean Constant score was 87.1 and the median Disabilities of the Arm, Shoulder and Hand score was 3.3. All fractures had united, except in one patient who developed an asymptomatic fibrous union. One patient had post-traumatic stiffness of the shoulder, which resolved with physiotherapy. None required re-operation. This technique produces good functional and radiological outcomes with a low prevalence of complications and routine implant removal is not necessary.

Genome sequence, comparative analysis, and population genetics of the domestic horse.

We report a high-quality draft sequence of the genome of the horse (Equus caballus). The genome is relatively repetitive but has little segmental duplication. Chromosomes appear to have undergone few historical rearrangements: 53% of equine chromosomes show conserved synteny to a single human chromosome. Equine chromosome 11 is shown to have an evolutionary new centromere devoid of centromeric satellite DNA, suggesting that centromeric function may arise before satellite repeat accumulation. Linkage disequilibrium, showing the influences of early domestication of large herds of female horses, is intermediate in length between dog and human, and there is long-range haplotype sharing among breeds.

Sex-for-crack-cocaine exchange, poor black women, and pregnancy.

A sample of 34 poor Black women who exchanged sex for crack was screened to discover if sex-for-crack exchanges resulted in pregnancies. Ethnographic interviews were conducted with women who became pregnant this way. Out of the 34 women, 18 reported sex-for-crack pregnancies, and more than half of that number became pregnant this way more than once. Twenty-nine pregnancies were reported. Only 2 women chose to have abortions. Interview transcripts were analyzed using qualitative data analytical procedures. The following three issues shaped the women's responses to sex-for-crack pregnancies: (a) severity of crack use, (b) religious beliefs, and (c) social organization patterns within poor Black communities. The findings have implications for drug treatment and child welfare policy.

Development and evaluation of the McKnight Risk Factor Survey for assessing potential risk and protective factors for disordered eating in preadolescent and adolescent girls.

OBJECTIVE: To describe the development, test-retest reliability, internal consistency, and convergent validity of the McKnight Risk Factor Survey-III (MRFS-III). The MRFS-III was designed to assess a number of potential risk and protective factors for the development of disordered eating in preadolescent and adolescent girls. METHOD: Several versions of the MRFS were pilot tested before the MRFS-III was administered to a sample of 651 4th through 12th- grade girls to establish its psychometric properties. RESULTS: Most of the test-retest reliability coefficients of individual items on the MRFS-III were r > .40. Alpha coefficients for each risk and protective factor domain on the MRFS-III were also computed. The majority of these coefficients were r > .60. High convergent validity coefficients were obtained for specific items on the MRFS-III and measures of self-esteem (Rosenberg Self-Esteem Scale) and weight concerns (Weight Concerns Scale). CONCLUSIONS: The test-retest reliability, internal consistency, and convergent validity of the MRFS-III suggest that it is a useful new instrument to assess potential risk and protective factors for the development of disordered eating in preadolescent and adolescent girls.

Cariostatic effect of a two-part fluoride dentifrice in rats.

This study compared the cariostatic effect of a two-part, fluoride-calcium-phosphate-containing prototype dentifrice (containing 1100 ppm F) to a conventional, clinically proven effective "gold standard" (1100 ppm F, USP Standard) and an Enamelon placebo dentifrice (0 ppm F) using a rat model. Three groups of 18 Crl:CDR(SD)BR rats were inoculated with S. sobrinus 27352 and fed MIT-200 for 35 days in a programmed feeder. Double-deionized water (DDW) was given ad libitum. The rats were treated twice daily with one two-part dentifrice. Just prior to treatment, each of the two parts of dentifrice were mixed 1:1 and applied undiluted. The rats were euthanized and their mandibular molars scored for caries using the Keyes quantification method. Shrestha SNP caries scores were then calculated. Non-parametric comparisons were done among treatments at the 0.05 level of significance using analyses based on ranks. The mean Shrestha SNP Caries Scores +/- standard deviations for the prototype dentifrice, USP standard and Enamelon placebo were 84.9 +/- 62.8, 101.3 +/- 66.3, and 181.2 +/- 100.1, respectively. Scores for the 1100 ppm F prototype treatment were significantly lower than the USP Standard and the Enamelon placebo. These results indicate that the new prototype dentifrice, containing fluoride-calcium-phosphate, increased the anti-caries efficacy in a rat model when compared with a fluoride-containing USP Standard dentifrice.

Evaluation of a computer-mediated eating disorder intervention program.

OBJECTIVE: This study evaluated an eating disorder intervention multimedia program modeled after self-help eating disorder treatment programs. It was hypothesized that women who completed the program would increase their body satisfaction and decrease their preoccupation with weight and frequency of disordered eating behaviors. METHOD: Participants were 57 undergraduate females randomly assigned to either the intervention or control group. Psychological functioning was assessed at baseline, at 3 months postintervention, and at 3 months follow-up. RESULTS: Intervention group subjects significantly improved their scores on all psychological measures over time. When compared to the control group, however, only the intervention group's improvements on the Body Shape Questionnaire were statistically significant. DISCUSSION: This study has demonstrated that minimally effective eating disorder intervention programs can be delivered. A revised program that eliminates interface problems and increases the structure of the intervention is likely to be even better received and more effective.

Factors associated with weight concerns in adolescent girls.

OBJECTIVE: This study examined the association of weight concerns with potential risk factors for the development of eating disorders. METHOD: A self-report survey was given to 103 elementary (Grades 4 and 5) and 420 middle (Grades 6-8) school students in Arizona and California. Of these, 78 elementary and 333 middle school students provided complete data and were used in the analyses. RESULTS: In a multivariate stepwise regression analysis, the importance that peers put on weight and eating was most strongly related to weight concerns in the elementary school girls, accounting for 34% of the variance after adjusting for site differences. Trying to look like girls/women on TV and in magazines as well as body mass index (BMI) entered the final model that accounted for 57% of the variance in weight concerns. In middle school, the importance that peers place on weight and eating was also the strongest predictor accounting for 33% of the variance followed by confidence, BMI, trying to look like girls/women on TV and in magazines, and being teased about weight. Together these variables accounted for 55% of the variance. DISCUSSION: Prevention programs aimed at reducing weight concerns need to address these factors.

Attachment style and weight concerns in preadolescent and adolescent girls.

OBJECTIVE: The purpose of this study was to assess the association between attachment style and weight concerns, a major risk factor for eating disorders, in preadolescent and adolescent girls. METHOD: Three hundred and five female elementary and middle school students completed measures of attachment style and weight concerns. RESULTS: Insecurely attached subjects reported higher weight concerns than did securely attached subjects. A greater proportion of insecurely attached subjects obtained "at risk" weight concerns scores than securely attached subjects. DISCUSSION: The findings suggest that attachment style may play an important role in the development of weight concerns, which, in turn, have been shown to be associated with the onset of eating disorders.

Description and effects of sequential behavior practice in teacher education.

This study examined the effects of a sequential behavior feedback protocol on the practice-teaching experiences of undergraduate teacher trainees. The performance competencies of teacher trainees were analyzed using an alternative opportunities for appropriate action measure. Data support the added utility of sequential (Sharpe, 1997a, 1997b) behavior analysis information in systematic observation approaches to teacher education. One field-based undergraduate practicum using sequential behavior (i.e., field systems analysis) principles was monitored. Summarized are the key elements of the (a) classroom instruction provided as a precursor to the practice teaching experience, (b) practice teaching experience, and (c) field systems observation tool used for evaluation and feedback, including multiple-baseline data (N = 4) to support this approach to teacher education. Results point to (a) the strong relationship between sequential behavior feedback and the positive change in four preservice teachers' day-to-day teaching practices in challenging situational contexts, and (b) the relationship between changes in teacher practices and positive changes in the behavioral practices of gymnasium pupils. Sequential behavior feedback was also socially validated by the undergraduate participants and Professional Development School teacher supervisors in the study.

Reports of stress: a comparison between eating disordered and non-eating disordered adolescents.

This study utilizes a unique method to examine reports of stressful life events provided by eating disordered and non-eating disordered adolescents. Subjects (all females) participated in a standardized procedure to obtain reports of stressful life events. The Life Events and Coping Inventory (LECI) was used to categorize reported stressors. Eating disorder subjects discussed more stressors than non-eating disorder subjects only when eating disorder events were included. Furthermore, eating disorder subjects reported more events that could not be classified within the LECI and were rated as non-normative. The findings point to the importance of qualitative rather than purely quantitative approaches to stressful life events assessment with adolescents.

Cyclic HIV protease inhibitors: synthesis, conformational analysis, P2/P2' structure-activity relationship, and molecular recognition of cyclic ureas.

High-resolution X-ray structures of the complexes of HIV-1 protease (HIV-1PR) with peptidomimetic inhibitors reveal the presence of a structural water molecule which is hydrogen bonded to both the mobile flaps of the enzyme and the two carbonyls flanking the transition-state mimic of the inhibitors. Using the structure-activity relationships of C2-symmetric diol inhibitors, computed-aided drug design tools, and first principles, we designed and synthesized a novel class of cyclic ureas that incorporates this structural water and preorganizes the side chain residues into optimum binding conformations. Conformational analysis suggested a preference for pseudodiaxial benzylic and pseudodiequatorial hydroxyl substituents and an enantiomeric preference for the RSSR stereochemistry. The X-ray and solution NMR structure of the complex of HIV-1PR and one such cyclic urea, DMP323, confirmed the displacement of the structural water. Additionally, the bound and "unbound" (small-molecule X-ray) ligands have similar conformations. The high degree of preorganization, the complementarity, and the entropic gain of water displacement are proposed to explain the high affinity of these small molecules for the enzyme. The small size probably contributes to the observed good oral bioavailability in animals. Extensive structure-based optimization of the side chains that fill the S2 and S2' pockets of the enzyme resulted in DMP323, which was studied in phase I clinical trials but found to suffer from variable pharmacokinetics in man. This report details the synthesis, conformational analysis, structure-activity relationships, and molecular recognition of this series of C2-symmetry HIV-1PR inhibitors. An initial series of cyclic ureas containing nonsymmetric P2/P2' is also discussed.

Improved cyclic urea inhibitors of the HIV-1 protease: synthesis, potency, resistance profile, human pharmacokinetics and X-ray crystal structure of DMP 450.

BACKGROUND: Effective HIV protease inhibitors must combine potency towards wild-type and mutant variants of HIV with oral bioavailability such that drug levels in relevant tissues continuously exceed that required for inhibition of virus replication. Computer-aided design led to the discovery of cyclic urea inhibitors of the HIV protease. We set out to improve the physical properties and oral bioavailability of these compounds. RESULTS: We have synthesized DMP 450 (bis-methanesulfonic acid salt), a water-soluble cyclic urea compound and a potent inhibitor of HIV replication in cell culture that also inhibits variants of HIV with single amino acid substitutions in the protease. DMP 450 is highly selective for HIV protease, consistent with displacement of the retrovirus-specific structural water molecule. Single doses of 10 mg kg-1 DMP 450 result in plasma levels in man in excess of that required to inhibit wild-type and several mutant HIVs. A plasmid-based, in vivo assay model suggests that maintenance of plasma levels of DMP 450 near the antiviral IC90 suppresses HIV protease activity in the animal. We did identify mutants that are resistant to DMP 450, however; multiple mutations within the protease gene caused a significant reduction in the antiviral response. CONCLUSIONS: DMP 450 is a significant advance within the cyclic urea class of HIV protease inhibitors due to its exceptional oral bioavailability. The data presented here suggest that an optimal cyclic urea will provide clinical benefit in treating AIDS if it combines favorable pharmacokinetics with potent activity against not only single mutants of HIV, but also multiply-mutant variants.

The effects of a sportsmanship curriculum intervention on generalized positive social behavior of urban elementary school students.

This study evaluated the effects of an elementary physical education curriculum in which development of positive social skills, including leadership and conflict-resolution behaviors, was the primary focus. A second goal was to determine possible generalization effects beyond the primary intervention setting. Students in two urban elementary physical education classes served as subjects, with a third class used as a comparison. The effects of the curriculum intervention were evaluated in the training setting and in the students' regular education classrooms using a multiple baseline across classrooms design. Results showed (a) an immediate increase in student leadership and independent conflict-resolution behaviors, (b) an increase in percentage of class time devoted to activity participation, and (c) decreases in the frequency of student off-task behavior and percentage of class time that students devoted to organizational tasks. Similar changes in student behavior were also observed in the regular classroom settings.