A guide to architecture for the public health workforce.

BACKGROUND: Public health and environmental challenges facing the world in the 21st century, including the ageing population, increasing urbanisation, rise of non-communicable diseases and climate instability, require an interdisciplinary response. A significant proportion of the population's time is spent indoors, be it at home, school, work or in leisure time; the work of an architect can cover all of these sectors, but their role in health and well-being remains an under explored area. OBJECTIVE: This article examines the architecture profession's potential to contribute to improved health and well-being of the population through healthier buildings and places. METHODOLOGY: This short communication adopts a descriptive approach. First, it maps the remit, skills and influence of the architecture profession and applies this to a well-accepted public health model, the prevention pyramid. Second, it uses themes identified by the Royal Society for Public Health to discuss ways to improve engagement with the architecture profession as part of the wider public health workforce. RESULTS: This article finds that the remit, skills and potential influence of architects places them in a key position to improve the health and well-being of the population. Despite this, there has been relatively little engagement between public health and this profession. Much more attention to date has been on integrating the planning sector with public health. CONCLUSION: Opportunities for improved engagement exist through partnership working, incorporating health into both undergraduate and postgraduate education and continuing professional development training, building the evidence base and developing architecture and health-related policy and legislation.

Concurrence of the strengths and difficulties questionnaire and developmental behaviour checklist among children with an intellectual disability.

BACKGROUND: The Strengths and Difficulties Questionnaire (SDQ) is widely used to measure emotional and behavioural problems in typically developing young people, although there is some evidence that it may also be suitable for children with intellectual disability (ID). The Developmental Behaviour Checklist - Parent version (DBC-P) is a measure of emotional and behavioural problems that was specifically designed for children and adolescents with an ID. The DBC-P cut-off has high agreement with clinical diagnosis. The aim of this study was to estimate the relationship between DBC-P and SDQ scores in a sample of children with ID. METHOD: Parents of 83 young people with ID aged 4-17 years completed the parent versions of the SDQ and the DBC-P. We evaluated the concurrent validity of the SDQ and DBC-P total scores, and the agreement between the DBC-P cut-off and the SDQ cut-offs for 'borderline' and 'abnormal' behaviour. RESULTS: The SDQ total difficulties score correlated well with the DBC-P total behaviour problem score. Agreement between the SDQ borderline cut-off and the DBC-P cut-off for abnormality was high (83%), but was lower for the SDQ abnormal cut-off (75%). Positive agreement between the DBC-P and the SDQ borderline cut-off was also high, with the SDQ borderline cut-off identifying 86% of those who met the DBC-P criterion. Negative agreement was weaker, with the SDQ borderline cut-off identifying only 79% of the participants who did not meet the DBC-P cut-off. CONCLUSION: The SDQ borderline cut-off has some validity as a measure of overall levels of behavioural and emotional problems in young people with ID, and may be useful in epidemiological studies that include participants with and without ID. However, where it is important to focus on behavioural profiles in children with ID, a specialised ID instrument with established psychometric properties, such as the DBC-P, may provide more reliable and valid information.

Syndrome specific modules to enhance the Stepping Stones Triple P public health intervention.

BACKGROUND: Service responses to behaviour phenotypes include care by expert clinicians, syndrome-specific clinics, disability-specific mental health services and generic mental health services. While these services contribute to care, they are often of limited accessibility. METHODS: We describe a population-wide public health intervention aimed at increasing the accessibility of services to the target population. Stepping Stones Triple P (SSTP) is a public health intervention of known efficacy in reducing behaviour problems when delivered to parents of children aged 0-12 with mixed developmental disabilities. RESULTS: The strategy we discuss involves enhancing SSTP with modules for specific causes of developmental disabilities including Down, Fetal Alcohol, Fragile X, Prader-Willi and Williams syndromes. CONCLUSIONS: We propose that enhancing SSTP with syndrome specific modules will increase the accessibility of support to families who have a child with a specific behaviour phenotype. We suggest that future research should confirm the public health impact of the modified SSTP programme using the RE-AIM framework.

MRSA and VRE colonization in solid organ transplantation: a meta-analysis of published studies.

The burden of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE) colonization among the increasing number of solid organ transplant patients has not been systematically explored. We searched PubMed and EMBASE for pertinent articles, performed a meta-analysis of prevalence across eligible studies and estimated the risk of ensuing MRSA or VRE infections relative to colonization status. We stratified effects in the pretransplant and posttransplant period. Twenty-three studies were considered eligible. Seventeen out of 23 (74%) referred to liver transplants. Before transplantation, the pooled prevalence estimate for MRSA and VRE was 8.5% (95% confidence interval [CI] 3.2­15.8) and 11.9% (95% CI 6.8­18.2), respectively. MRSA estimate was influenced by small studies and was lower (4.0%; 95% CI 0.4­10.2) across large studies (>200 patients). After transplantation, the prevalence estimates were 9.4% (95% CI 3.0­18.5) for MRSA and 16.2% (95% CI 10.7­22.6) for VRE. Pretransplant as well as posttransplant MRSA colonization significantly increased the risk for MRSA infections (pooled risk ratio [RR] 5.51; 95% CI 2.36­12.90 and RR 10.56; 95% CI 5.58­19.95, respectively). Pretransplant and posttransplant VRE colonization were also associated with significant risk of VRE infection (RR 6.65; 95% CI 2.54­17.41 and RR 7.93; 95% CI 2.36­26.67, respectively). Solid organ transplantation is a high-risk setting for MRSA and VRE colonization, and carrier state is associated with infection. Upgraded focus in prevention and eradication strategies is warranted.

What happens post-pilot testing? A model for revising a disability awareness and competency training program.

Disability awareness and competency trainings are an important component of addressing ableism and health equity in the health promotion context. This commentary describes our process of developing, implementing, and refining a disability competency training, the Inclusive Community Exercise Training, for community-based group exercise instructors. The training originated from a partnership between academic researchers, community organizations, and individuals with disabilities. After initial pilot testing, we used feedback from participants to enhance the training. To optimize successful dissemination of this training, we utilized the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, which is widely used in public health. The revision process focused on generalizing content to suit a wider audience, utilizing an eLearning platform for dissemination, and optimizing interactivity to improve learning effectiveness. The commentary emphasizes the lessons learned and the significance of systematic program revision, considering diverse expertise, content tailoring, and the benefits of accessible eLearning platforms.

Fatal cardiac and renal allograft rejection with lenalidomide therapy for light-chain amyloidosis.

We describe a patient who underwent a successful heart and kidney transplant for light-chain amyloidosis. She had an excellent hematologic response to bortezomib/dexamethasone therapy. Follow-up therapy with lenalidomide was started, and the patient quickly had a fatal allograft rejection of the heart and kidney. We present evidence to support the theory that lenalidomide, a known immunomodulator, may have stimulated the immune system and precipitated the fatal rejection episode.

Niche differentiation and colonization of a novel environment by an asexual parasitic wasp.

How do asexual taxa become adapted to a diversity of environments, and how do they persist despite changing environmental conditions? These questions are linked by their mutual focus on the relationship between genetic variation, which is often limited in asexuals, and the ability to respond to environmental variation. Asexual taxa originating from a single ancestor present a unique opportunity to assess rates of phenotypic and genetic change when access to new genetic variation is limited to mutation. Diachasma muliebre is an asexual Hymenopteran wasp that is geographically and genetically isolated from all sexual relatives. D. muliebre attack larvae of the western cherry fruit fly (Rhagoletis indifferens), which in turn feed inside bitter cherry fruit (Prunus emarginata) in August and September. R. indifferens has recently colonized a new host plant with an earlier fruiting phenology (June/July), domesticated sweet cherries (P. avium), and D. muliebre has followed its host into this temporally earlier niche. We tested three hypotheses: 1) that all D. muliebre lineages originate from a single asexual ancestor; 2) that different D. muliebre lineages (as defined by unique mtDNA haplotypes) have differentiated on their ancestral host in an important life-history trait, eclosion timing; and 3) that early-eclosing lineages have preferentially colonized the new sweet cherry niche. We find that mitochondrial COI and microsatellite data provide strong support for a single ancestral origin for all lineages. Furthermore, COI sequencing revealed five mitochondrial haplotypes among D. muliebre, and individual wasps possessing one distinctive mitochondrial haplotype (haplotype II) eclosed as reproductive adults significantly earlier than wasps with all other haplotypes. In addition, this early-eclosing lineage of D. muliebre is one of two lineages that have colonized the P. avium habitat, consistent with the preferential colonization hypothesis. These data suggest that D. muliebre has evolved adaptive phenotypic variation despite limited genetic variation, and that this variation has subsequently allowed an expansion of some wasps into a novel habitat. The D. muliebre system may allow for in-depth study of adaptation and long-term persistence of asexual taxa.

Design of a single-tube, endpoint, linear-after-the-exponential-PCR assay for 17 pathogens associated with sepsis.

AIMS: The goal of this study was to construct a single-tube multiplex molecular diagnostic assay using linear-after-the-exponential (LATE)-PCR for the detection of 17 microbial pathogens commonly associated with septicaemia. METHODS AND RESULTS: The assay described here detects 17 pathogens associated with sepsis via amplification and analysis of gene-specific sequences. The pathogens and their targeted genes were: Klebsiella spp. (phoE); Acinetobacter baumannii (gyrB); Staphylococcus aureus (spa); Enterobacter spp. (thdF); Pseudomonas aeruginosa (toxA); coagulase-negative staphylococci (tuf), Enterococcus spp. (tuf); Candida spp. (P450). A sequence from an unidentified gene in Lactococcus lactis, served as a positive control for assay function. LATE-PCR was used to generate single-stranded amplicons that were analysed at endpoint over a wide range of temperatures in four fluorescent colours. Each target was detected by its pattern of hybridization to a sequence-specific low-temperature fluorescent probe derived from molecular beacons. CONCLUSIONS: All 17 microbial targets were detected in samples containing low numbers of pathogen genomes in the presence of high levels of human genomic DNA. SIGNIFICANCE AND IMPACT OF THE STUDY: This assay used new technology to achieve an advance in the field of molecular diagnostics: a single-tube assay for detection of pathogens commonly responsible for septicaemia.

Design and construction of a single tube, quantitative endpoint, LATE-PCR multiplex assay for ventilator-associated pneumonia.

AIMS: The goal of this study was to develop a molecular diagnostic multiplex assay for the quantitative detection of microbial pathogens commonly responsible for ventilator-associated pneumonia (VAP) and their antibiotic resistance using linear-after-the-exponential polymerase chain reaction (LATE-PCR). METHOD AND RESULTS: This multiplex assay was designed for the quantitative detection and identification of pathogen genomic DNA of methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii, Pseudomonas aeruginosa, plus a control target from Lactococcus lactis. After amplification, the single-stranded amplicons were detected simultaneously in the same closed tube by hybridization to low-temperature molecular beacon probes labelled with four differently coloured fluorophores. The resulting hybrids were then analysed by determining the fluorescence intensity of each of the four fluorophores as a function of temperature. CONCLUSIONS: This LATE-PCR single tube multiplex assay generated endpoint fluorescent contours that allowed identification of all microbial pathogens commonly responsible for VAP, including MRSA. The assay was quantitative, identifying the pathogens present in the sample, no matter whether there were as few as 10 or as many 100 000 target genomes. SIGNIFICANCE AND IMPACT OF THE STUDY: This assay is rapid, reliable and sensitive and is ready for preclinical testing using samples recovered from patients suffering from ventilator-associated pneumonia.

Verification of monoplex and multiplex linear-after-the-exponential PCR gene-specific sepsis assays using clinical isolates.

AIMS: To verify monoplex and multiplex gene-specific linear-after-the-exponential polymerase chain reaction (LATE-PCR) assays for identifying 17 microbial pathogens (i.e., Klebsiella sp., Acinetobacter baumannii, Staphylococcus aureus, Enterobacter sp., Pseudomonas aeruginosa, coagulase negative staphylococci, Enterococcus sp., Candida sp.) commonly associated with septicaemia using clinical isolates. METHODS AND RESULTS: Clinical isolates of each target pathogen were collected from the University of California, Davis Medical Center (UCDMC) microbiology laboratory. Five microlitres (µl) of each culture suspension (1 × 10(8) CFU ml(-1) ) were added to 20 µl of monoplex mastermix. DNA extracted from clinical isolates was tested in multiplex. Monoplex assays demonstrated 100% sensitivity at this input level, except Enterobacter cloacae (2.7%), Ac. baumannii (57%) and Ps. aeruginosa (97.8%). All clinical isolates were positive in multiplex, with the exception of two Ac. baumannii, two Klebsiella oxytoca and two Candida parapsilosis isolates. CONCLUSIONS: Sixteen pathogens can be identified by monoplex LATE-PCR assays with sensitivities ≥ 97.8%. The multiplex assay demonstrated 91.4% sensitivity when tested with DNA extracted from 70 different target strains. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates the potential of LATE-PCR to serve as an adjunct to culture if the reagents are optimized for sensitivity. Results warrant further testing through analytical and clinical validation of the multiplex assay.

Does apolipoprotein E genotype modify the clinical expression of ALS?

BACKGROUND: The presence of the apolipoprotein E (ApoE) 4 genotype is associated with an earlier age of onset for Alzheimer's disease (AD) and several other neurodegenerative disorders. The objective of this study was to investigate the effect of ApoE genotypes on the clinical course of amyotrophic lateral sclerosis (ALS). METHODS: Eight hundred and fifty-two consecutive patients with sporadic ALS evaluated at a tertiary care center were investigated for the effect of ApoE genotype on age of onset, rate of motor disease progression, cognitive functioning, and survival in ALS. RESULTS: The frequencies of individual ApoE genotypes did not differ between patients with ALS and ALS-free Caucasian populations. Patients with different ApoE genotypes did not differ in the age of onset for ALS (years) (ApoE2 = 57.8 ± 13.7, ApoE3 = 57.3 ± 13.7, ApoE4 = 57.7 ± 13.2; P = 0.97), the rate of disease progression (Appel ALS score/month) (ApoE2 = 2.91 ± 2.66, ApoE3 = 2.67 ± 2.66, ApoE4 = 2.61 ± 2.47; P = 0.89), cognitive status (% cognitively impaired) (ApoE2 = 31.7, ApoE3 = 26.8, ApoE4 = 34.3, P = 0.28), or survival in years (ApoE2 = 3.79 ± 3.70, ApoE3 = 3.17 ± 2.27, ApoE4 = 3.05 ± 1.75; P = 0.85). CONCLUSIONS: Our results suggest that ApoE genotype does not modify clinical course of sporadic ALS, in stark contrast to the influence of ApoE genotype on the disease course of AD and other neurodegenerative disorders.

Prospective epidemiological study of the prevalence of human leukocyte antigen (HLA)-B*5701 in HIV-1-infected UK subjects.

OBJECTIVES: Human leukocyte antigen (HLA)-B(*)5701 is strongly associated with developing a hypersensitivity reaction to abacavir (ABC) in White and Hispanic subjects. Across the UK, limited data exist on HLA-B(*)5701 prevalence in HIV-1-infected subjects. We determined HLA-B(*)5701 prevalence in the general HIV-1-infected population and in specific ethnic groups, particularly Black Africans who, in general, exhibit greater genetic diversity. We also compared HLA-B(*)5701 results obtained from local laboratories with those from a central provider. DESIGN AND METHODS: Multi-centre, observational study. All HIV-1-infected adult individuals receiving care at participating centres were eligible, irrespective of treatment status or prior exposure to ABC. Subjects provided samples for HLA-B(*)5701 assessment by both local (blood) and central laboratories (buccal swabs). HLA-B(*)5701 prevalence was adjusted to represent the ethnic group composition of the general UK population, and by main ethnic group. RESULTS; From eight UK centres, 1494 subjects [618 (41%) White, 770 (52%) Black] were recruited. Eighty-nine per cent of Black subjects reported an immediate country of origin in Africa. Overall adjusted HLA-B(*)5701 prevalence was 4.55% [95% confidence interval (CI) 3.49% to 5.60%]. Among White subjects, prevalence was 7.93% (CI 5.80% to 10.06%). Among Black subjects, only two (both Ugandan) were HLA-B(*)5701 positive giving a rate of 0.26% (CI 0.07% to 0.94%). CONCLUSIONS: HLA-B(*)5701 prevalence was similar to previously reported rates in White HIV-infected subjects but considerably lower than that reported in Black HIV-1-infected subjects, as a result of the large proportion of Black African subjects.

Application of the Droplet Digital Polymerase Chain Reaction (ddPCR) Platform for Detection and Quantification of Vertebrate Host DNA in Engorged Mosquitoes.

Hematophagous arthropod bloodmeal identification has remained a challenge in the field of vector biology, but these studies are important to understand blood feeding patterns of arthropods, spatial, and temporal patterns in arbovirus transmission cycles, and risk of human and veterinary disease. We investigated the use of an existing vertebrate primer set for use on the droplet digital polymerase chain reaction (ddPCR) platform, to explore the use of this technology in the identification and quantification of vertebrate DNA in mosquito blood meals. Host DNA was detectable 48-h post-engorgement in some mosquitoes by ddPCR, compared with 24-h post-engorgement using traditional PCR. The capability of ddPCR for absolute quantification of template DNA offers unique potential applications of this new technology to field studies on the ecology of vector-borne diseases, but currently with limited scope.

A cost comparison of two strategies for treating stage IB2 cervical cancer.

Patients with stage IB2 cervical cancer at our institution are treated primarily with definitive chemoradiation, or chemoradiation followed by adjuvant hysterectomy. We sought to compare the cost differences associated with these two strategies. We identified all patients with stage IB2 cervical cancer who received their entire treatment regimen at our institution between 1995 and 2004. All patients received a combination of chemotherapy, external beam radiation, and one brachytherapy procedure, followed by either a second brachytherapy procedure or a simple hysterectomy. We retrieved cost data associated with hospitalization for the completion of respective treatment, including pharmacy, laboratory and pathology, radiation, and operating room services, as well as the costs of supplies and room and board. We identified 46 patients with stage IB2 cervical cancer, 23 who received a second brachytherapy procedure and 23 who underwent simple hysterectomy. Patients displayed similar demographics and similar disease characteristics including initial tumor diameter and histology. The cost of care for adjuvant hysterectomy group was greater ($8,316.70 vs 5,508.70, P < 0.0001). Specific differences included higher operating room costs ($1520 vs 414, P < 0.0001), pharmacy costs ($675 vs 342, P < 0.0001), and laboratory/pathology costs ($597 vs 89, P < 0.0001). We conclude that definitive chemoradiation appears to be associated with lower costs for management of stage IB2 cervical cancer when compared to simple adjuvant hysterectomy.

Chemoradiation with and without adjuvant extrafascial hysterectomy for IB2 cervical carcinoma.

The optimal treatment strategy for stage IB2 cervical carcinoma that maximizes survival while minimizing toxicity remains controversial. The purpose of this study was to compare survival and toxicity in stage IB2 cervical cancer patients treated with chemoradiation and adjuvant extrafascial hysterectomy (cRT + H) versus definitive chemoradiation (cRT). Data were abstracted from patients with IB2 cervical carcinoma primarily treated at a single institution from January 1994 to December 2004. All patients received chemotherapy concurrent with external beam radiation therapy. Patients were subsequently treated with either a single low-dose rate brachytherapy applicator followed by adjuvant extrafascial hysterectomy (n = 24) or a second brachytherapy application to complete full-dose definitive chemoradiation (n = 30). Analyses were conducted using Kaplan-Meier survival and Chi-square statistics. Groups did not differ demographically with the exception of smoking. Smokers were significantly (P = 0.04) more likely to have been treated with definitive chemoradiation. Median tumor size was similar between groups. There was no difference in overall or disease-free survival between patients who received cRT + H versus cRT (P = 0.82 and 0.75, respectively). All recurrences in the cRT arm were in smokers. There were two grade 3-4 toxicities in each group. No treatment-related deaths occurred. In this small retrospective cohort study, we observed no difference in survival between patients treated with cRT + H versus cRT. These data complement published results of Gynecologic Oncology Group studies in patients with IB2 cervical cancer. Definitive comparison between the two treatment strategies would require a randomized prospective trial with stratification based on smoking.

Spectrum of immunodeficiencies with Hodgkin's disease.

The role of six suppressor mechanisms upon T and B cell responses was studied on 17 untreated patients with Hodgkin's disease. Proliferative hyporesponsiveness to mitogen was greatly impaired in 8 of the 13 patients. 10 of these patients had an excessive degree of suppression by cells that adhered to foreign surfaces. Suppression by adherent cells correlated with impairment of proliferative responses and, in some instances, suppression was largely inhibited with indomethacin. Likewise, adherent cells suppressed immunoglobulin synthesis. A correlation was evident between suppression of T and B cell responses by adherent mononuclear leukocytes from individual patients. This suppression coincided with elevated percentages of monocytes in the patient mononuclear cell preparations. This excess of monocytes was not the result of a circulating monocytosis. The monocyte excess may have been acquired during isopyknic cell separation. A second form of suppression was observed in 5 of the 11 patients affected by a lymphocyte that neither adhered to glass wool nor required preactivation. It did not inhibit allogeneic lymphocytes, which contrasts with the suppressor abnormality of monocytoid cells.