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Healthcare-associated infections (HAIs) are a serious concern in the NICU. Alternatives or supplements to manual cleaning are increasingly being explored, including ultraviolet (UV) disinfection technologies. A recently-developed hybrid lighting system technology, designed to provide both visible white light and disinfecting UV-A (λmax = 366 nm) radiation, was retrofitted into a hospital newborn intensive care unit (NICU). The UV-A dosing was set to levels calculated to be safe for continuous adult occupation. The results showed that eight-hour exposures of 3 W m-2 on counter surfaces were effective for suppressing bacteria that commonly cause HAIs in the NICU. Although UV-A is not as effective at inactivating viruses as UV-C, it is safe for use while space is occupied, making it a promising technology for consideration in certain areas of the NICU.

Vaginal mucosal surfaces naturally offer some protection against sexually transmitted infections (STIs) including Human Immunodeficiency Virus-1, however topical preventative medications or vaccine designed to boost local immune responses can further enhance this protection. We previously developed a novel mucosal vaccine strategy using viral vectors integrated into mouse dermal epithelium to induce virus-specific humoral and cellular immune responses at the site of exposure. Since vaccine integration occurs at the site of cell replication (basal layer 100-400 micrometers below the surface), temporal epithelial thinning during vaccine application, confirmed with high resolution imaging, is desirable. In this study, strategies for vaginal mucosal thinning were evaluated noninvasively using optical coherence tomography (OCT) to map reproductive tract epithelial thickness (ET) in macaques to optimize basal layer access in preparation for future effective intravaginal mucosal vaccination studies. Twelve adolescent female rhesus macaques (5-7kg) were randomly assigned to interventions to induce vaginal mucosal thinning, including cytobrush mechanical abrasion, the chemical surfactant spermicide nonoxynol-9 (N9), the hormonal contraceptive depomedroxyprogesterone acetate (DMPA), or no intervention. Macaques were evaluated at baseline and after interventions using colposcopy, vaginal biopsies, and OCT imaging, which allowed for real-time in vivo visualization and measurement of ET of the mid-vagina, fornices, and cervix. P value ≤0.05 was considered significant. Colposcopy findings included pink, rugated tissue with variable degrees of white-tipped, thickened epithelium. Baseline ET of the fornices was thinner than the cervix and vagina (p

Background: Stem cells offer great hope and promise as a potential treatment for human diseases. The aim of this study was to gain insight into the public perception of stem cells for neurological conditions. Materials & methods: A paper-based questionnaire was administered to all attendees of a free, public stem cell forum. Results: Of 203 respondents, >95% believe that stem cells have the potential to treat neurological conditions. There was also high support (92%) for the use of embryonic/fetally derived cells, and 67% of respondents indicated a high likelihood to participate in a clinical trial of stem cell treatment(s), indicating overall support for research and translation. Conclusion: Our data demonstrates a positive perception of stem cell treatments for neurological conditions in our cohort.

There has been an increase in the number of people with learning disabilities admitted to mainstream mental health services, who are reported to be at greater risk of physical and mental health problems than the general population. Mental health professionals from all disciplines report minimal pre-registration education in this field. This study sought to develop a multidisciplinary competency tool for use in the care of this patient group. A review of the literature informed the topic guide for focus groups (n=2) with experienced mental health practitioners (n=19). Thematic analysis identified overarching and sub-themes, and a pilot of the tool was created in diagrammatic format. Expert interviews (n=18) were conducted to validate emergent overarching and sub-themes. The major themes that emerged were: positive behavioural support, risk and safety, management of mental illness and communication. Clinical competencies are increasingly generated to ensure accountability but they must also enhance the patient experience. Traditional presentation methods of competencies may render them utilitarian (via lists and Likert scales) and stifle clinical innovation. To facilitate competency development, a pictorial ‘template for action: learning disabilities’ was developed.

The human cervicovaginal microbiota resides at an interface between the host and the environment and may affect susceptibility to disease. Puerto Rican women have high human papillomavirus (HPV) infection and cervical cancer rates. We hypothesized that the population structure of the cervicovaginal bacterial and fungal biota changed with cervical squamous intraepithelial lesions and HPV infections. DNA was extracted from cervix, introitus, and anal sites of 62 patients attending high-risk San Juan clinics. The 16S rRNA V4 region and ITS-2 fungal regions were amplified and sequenced using Illumina technology. HPV genotyping was determined by reverse hybridization with the HPV SPF10-LiPA25 kit. HPV prevalence was 84% of which ∼44% subjects were infected with high-risk HPV, ∼35% were co-infected with as many as 9 HPV types and ∼5% were infected with exclusively low-risk HPV types. HPV diversity did not change with cervical dysplasia. Cervical bacteria were more diverse in patients with CIN3 pre-cancerous lesions. We found enrichment of Atopobium vaginae and Gardnerella vaginalis in patients with CIN3 lesions. We found no significant bacterial biomarkers associated with HPV infections. Fungal diversity was significantly higher in cervical samples with high-risk HPV and introitus samples of patients with Atypical Squamous Cells of Undetermined Significance (ASCUS). Fungal biomarker signatures for vagina and cervix include Sporidiobolaceae and Sacharomyces for ASCUS, and Malassezia for high-risk HPV infections. Our combined data suggests that specific cervicovaginal bacterial and fungal populations are related to the host epithelial microenvironment, and could play roles in cervical dysplasia.

Importance Cerebral palsy describes the most common physical disability in childhood and occurs in 1 in 500 live births. Historically, the diagnosis has been made between age 12 and 24 months but now can be made before 6 months’ corrected age. Objectives To systematically review best available evidence for early, accurate diagnosis of cerebral palsy and to summarize best available evidence about cerebral palsy–specific early intervention that should follow early diagnosis to optimize neuroplasticity and function. Evidence Review This study systematically searched the literature about early diagnosis of cerebral palsy in MEDLINE (1956-2016), EMBASE (1980-2016), CINAHL (1983-2016), and the Cochrane Library (1988-2016) and by hand searching. Search terms included cerebral palsy , diagnosis , detection , prediction , identification , predictive validity , accuracy , sensitivity , and specificity . The study included systematic reviews with or without meta-analyses, criteria of diagnostic accuracy, and evidence-based clinical guidelines. Findings are reported according to the PRISMA statement, and recommendations are reported according to the Appraisal of Guidelines, Research and Evaluation (AGREE) II instrument. Findings Six systematic reviews and 2 evidence-based clinical guidelines met inclusion criteria. All included articles had high methodological Quality Assessment of Diagnostic Accuracy Studies (QUADAS) ratings. In infants, clinical signs and symptoms of cerebral palsy emerge and evolve before age 2 years; therefore, a combination of standardized tools should be used to predict risk in conjunction with clinical history. Before 5 months’ corrected age, the most predictive tools for detecting risk are term-age magnetic resonance imaging (86%-89% sensitivity), the Prechtl Qualitative Assessment of General Movements (98% sensitivity), and the Hammersmith Infant Neurological Examination (90% sensitivity). After 5 months’ corrected age, the most predictive tools for detecting risk are magnetic resonance imaging (86%-89% sensitivity) (where safe and feasible), the Hammersmith Infant Neurological Examination (90% sensitivity), and the Developmental Assessment of Young Children (83% C index). Topography and severity of cerebral palsy are more difficult to ascertain in infancy, and magnetic resonance imaging and the Hammersmith Infant Neurological Examination may be helpful in assisting clinical decisions. In high-income countries, 2 in 3 individuals with cerebral palsy will walk, 3 in 4 will talk, and 1 in 2 will have normal intelligence. Conclusions and Relevance Early diagnosis begins with a medical history and involves using neuroimaging, standardized neurological, and standardized motor assessments that indicate congruent abnormal findings indicative of cerebral palsy. Clinicians should understand the importance of prompt referral to diagnostic-specific early intervention to optimize infant motor and cognitive plasticity, prevent secondary complications, and enhance caregiver well-being.

Objectives To examine the funding for cerebral palsy (CP) research in Australia, as compared with the National Institutes of Health (NIH). Design Observational study. Setting For Australia, philanthropic funding from Cerebral Palsy Alliance Research Foundation (CPARF) (2005–2015) was compared with National Health and Medical Research Council (NHMRC, 2000–2015) and Australian Research Council (ARC, 2004–2015) and CPARF and NHMRC funding were compared with NIH funding (USA). Participants Cerebral Palsy researchers funded by CPARF, NHMRC or NIH. Results Over 10 years, total CPARF philanthropic funding was $21.9 million, including people, infrastructure, strategic and project support. As competitive grants, CPARF funded $11.1 million, NHMRC funded $53.5 million and Australian Research Council funded $1.5 million. CPARF, NHMRC and NIH funding has increased in real terms, but only the NIH statistically significantly increased in real terms (mean annual increase US$4.9 million per year, 95% CI 3.6 to 6.2, p

The number of clinically relevant gene-based guidelines and recommendations pertaining to drug prescribing continues to grow. Incorporating gene-drug interaction information into the drug-prescribing process can help optimize pharmacotherapy outcomes and improve patient safety. However, pharmacogenomic implementation barriers exist such as integration of pharmacogenomic results into electronic health records (EHRs), development and deployment of pharmacogenomic decision support tools to EHRs, and feasible models for establishing ambulatory pharmacogenomic clinics. We describe the development of pharmacist-managed pharmacogenomic services within a large health system. The Clinical Pharmacogenetics Implementation Consortium guidelines for HLA-B*57:01-abacavir, HLA-B*15:02-carbamazepine, and TPMT-thiopurines (i.e., azathioprine, mercaptopurine, and thioguanine) were systematically integrated into patient care. Sixty-three custom rules and alerts (20 for TPMT-thiopurines, 8 for HLA-B*57:01-abacavir, and 35 for HLA-B*15:02-anticonvulsants) were developed and deployed to the EHR for the purpose of providing point-of-care pharmacogenomic decision support. In addition, a pharmacist and physician-geneticist collaboration established a pharmacogenomics ambulatory clinic. This clinic provides genetic testing when warranted, result interpretation along with pharmacotherapy recommendations, and patient education. Our processes for developing these pharmacogenomic services and solutions for addressing implementation barriers are presented.

Sail training refers to sea voyages designed to foster personal and social change. Such training has mainly involved young people but may have the potential to benefit adults who are recovering from drug and alcohol addiction. During the voyage described here clients in drug rehabilitation centres across the UK were given the opportunity to participate in a 5-day sail training voyage. Pre- and post-voyage interviews were conducted with 11 clients to explore their experiences of being selected and participating in this voyage. Clients enjoyed the experience and found it to be beneficial, promoting self-insight, new life plans and social skills development. Living in an unfamiliar, potentially dangerous and inescapable environment necessitating close proximity to others and teamwork under the supervision of expert authority figures generated bonding with and caring for others; as well as the development of new competencies and greater self-confidence. The findings suggest that sail training can be beneficial to clients in recovery from addiction and highlight key features that may optimise effectiveness.

Depression is a burdening disease worldwide despite the availability of published clinical guidelines, neces- sitating an expansion of treatment options. Relaxation training (RT) is an easily accessible treatment that receives limited research attention on its effectiveness for treating depression. This systematic review retrieved eight studies with mixed methods to evaluate the effectiveness of RT in treating depression using qualitative thematic analysis. Findings showed that RT is a simple, low-cost treatment that can alleviate self-reported mild depressive symptoms in young populations. It is a coping skill that boosts individuals' sense of self-efficacy, counteracting the effects of depression. RT plays the role of a common adjuvant treatment that is endorsed and used by practitioners, non-professional personnel, patients and the general public. With further evidence on its long-term effects and the suitable recipients, RT can be promoted which can possibly lessen the burden of depression.

Summary This paper examines the effect of the global financial crisis on the delivery of HIV and AIDS-related services in Malawi. It does so by examining the direct effect of the crisis on Malawi’s economy and the financing experience of civil society organization involved in the delivery of services. The paper finds that Malawi’s economy survived the global crisis relatively unscathed but there was clear evidence of a sharp deterioration in funding for agencies engaged in HIV- and AIDS-related programs in 2008 and 2009. Thus the gap between service delivery and service demand appears to have increased considerably in those years.

Lighting plays a pivotal role in neonatal intensive care units (NICUs). Lighting must accommodate 3 distinctly different groups: newborns, health care professionals, and families. Although wards housing several infants still exist, many NICUs are being designed as a series of single-family rooms. All individuals interacting in these environments have a right to expect a supportive lighting system. Lighting should be quiet, reliable, efficient, and maintenance-free. Lighting should be as simple to change as the moment-to-moment needs of the different populations change. The intent of this article is to provide relevant direction as it pertains to lighting design in today's NICUs. After reviewing the lighting accommodations required for 3 distinctly different groups of people—infants, families, and staff—basic concepts deemed important for design considerations in the NICU are outlined. This article puts forth a goal-oriented approach to ensuring a successful lighting result, and refers to useful lighting resources.

Sentinel lymph node (SLN) status is highly predictive of overall axillary lymph node involvement in breast cancer. Historically, SLN-positive patients have undergone axillary lymph node dissection in a second surgery. Intraoperative SLN analysis could reduce the cost and complications of a second surgery; however, existing histopathological methods lack standardization and exhibit poor sensitivity. Rapid molecular methods may lead to improved intraoperative diagnosis of SLN metastasis. In this study, we used a genome-wide gene expression analysis of breast and other tissues to identify seven putative markers for detecting breast cancer metastasis. We assessed the utility of these markers for identifying clinically actionable metastases in lymph nodes through reverse transcriptase-polymerase chain reaction analysis of SLNs from 254 breast cancer patients. Polymerase chain reaction signals were compared to pathology on a per-patient basis. The optimal two-gene combination, mammaglobin and cytokeratin 19, detected clinically actionable metastasis in breast SLNs with 90% sensitivity and 94% specificity. Application of stringent criteria for identifying presumptive hematoxylin- and eosin-positive samples increased sensitivity and specificity to 91 and 97%, respectively. This study represents the first comprehensive demonstration of the utility of gene expression markers for detecting clinically actionable breast metastases. An intraoperative molecular assay using these markers has the potential to significantly reduce second surgeries for patients undergoing SLN dissection.

The United Kingdom Central Council for Nursing, Midwifery and Health Visiting (UKCC) has for many years sought to promote the development of research knowledge and skills in registered nurses and has based its efforts on a particular model of the professional practitioner. This model has each registered nurse as a competent finder, appraiser and utilizer of research evidence. It has a vision of all registered nurses acting as autonomous practitioners, able to adapt their practice according to their own expert assessment of current research findings. Through its powers of strategic direction of nurse training and education, the UKCC has required the national boards to have approved education institutions prepare nurses for this role at both pre- and post-registration level. In this paper we argue that this model has proven ineffective. Our argument suggests that the technical complexity of research, and the skills and time required to find and integrate research evidence, renders such a model unattainable. Evidence from studies of clinical nurses indicates that little progress has in any case been made. Furthermore, the development of the apparatus of clinical governance and the basis of professional accountability further undermine the grounds for this approach. A modified approach is advocated based on the development of research specialists within nursing and the greater use of research-based clinical guidelines.

Registration of innovative biologics in Emerging Markets (EMs) poses many opportunities and challenges. The BRIC-MT countries (Brazil, Russia, India, China, Mexico, and Turkey) that are the fastest growing markets and regulators in these countries have imposed certain requirements, including the need for local clinical studies, for registration of biologics. The regulatory landscape in these countries is rapidly evolving, which necessitates an up-to-date understanding of such requirements. There is growing evidence which suggests that race, after accounting for body weight differences, may not influence the pharmacokinetics of biologics to the same extent that it does for small molecules. Thus, the requirements for clinical pharmacology trials in EMs are driven mainly by regulatory needs set forth by local Ministry of Health. In addition to the clinical Phase I to III studies done in the global program that supports registration in large geographies, countries such as China require local single and multiple dose Phase I studies. Participating in global studies with clinical sites within their country may be sufficient for some markets, while other regulators may be satisfied with a Certificate of Pharmaceutical Product. This paper discusses the current requirements for registration of innovative biologics in key EMs.

In this article five writers survey and analyse the impact on the British landscape of the foot and mouth outbreak of 2001. Beginning with the human dimension, Angus Winchester chronicles the devastating impact of the disease on the communities of Cumbria. Moving away from the epicentre of the crisis, Tom Williamson argues that the destruction of the remnant livestock industry in the predominantly arable areas of southern and eastern England would also be a disaster – visually, archaeologically and botanically. Writing from the ecologist's perspective, Ian Simmons offers some models of how agroecosystems might develop as a result of the contraction of pastoral farming. Robert White delineates the effects of the epidemic on the countryside's archaeological sites, farm buildings and nature reserves. He also argues, along with Clive Potter, that the effects of the disease on the economy of the countryside might have given rise to its most lasting legacy: a shift to a more integrated approach to the r...

Communities of fungal endophytes from roots, stems and leaves of the introduced grass Hyparrhenia hirta (Coolatai grass) and the native species Bothriochloa macra (redgrass) were compared at two sites to identify characteristics that may be associated with invasiveness of H. hirta. The most frequently isolated fungi from both hosts were species of Nigrospora, Alternaria, Cladosporium, Phoma, Epicoccum, Fusarium and Periconia. Most of these occurred at a similar frequency in the two hosts, although Nigrospora sphaerica was much more frequently isolated from H. hirta at both sites. There was little support for the hypothesis that the introduced species (H. hirta) would have a less diverse endophyte community than the native species. There was a greater degree of dominance by the most frequent species in communities from H. hirta than from B. macra, leading to lower diversity indices, but no significant difference in species richness. Cluster analysis of the endophyte communities suggested that host had a greater influence than site on community structure, and that this was expressed mostly in the relative frequency of fungi isolated from stems and leaves, with very similar fungal communities present in the roots of both species at both sites. Analysis of co-occurrence showed no evidence that competition among fungi affected community structure within individual plants. The dominance of N. sphaerica in H. hirta was therefore due to fungus–plant interactions rather than fungus–fungus interactions. Interactions with N. sphaerica could potentially affect the population ecology of H. hirta.

The extract of human peripheral blood lymphocytes and monocytes treated with Triton X-100, in direct- and competitive-binding studies, with 10(-6)-10(-2) M [14C]histamine contained a low-affinity binding site whose dissociation constant (Kd 1.8 X 10(-4) M) was commensurate with the concns of histamine (10(-6)-10(-3) M) that result from mast cell and basophil degranulation. Binding was enhanced by millimolar concns of divalent cations and by raising the incubation temp from 4 to 37 degrees C. It was inhibited by trypsin, EDTA, agents interacting with thiol groups, and by Triton X-100 concns greater than 0.2%. Thus a low-affinity histamine receptor that maintains its ligand-binding properties after solubilization from the cell surface was identified.

Twenty-two patients were investigated during acute attacks of erythema nodosum with a series of tests for circulating immune complexes. Nineteen had bilateral hilar lymphadenopathy and were considered to have sarcoidosis. Evidence of circulating immune complexes was found in 18, out of 22 patients (including 15 out of the 19 cases of sarcoidosis). The most frequent abnormality was the detection of elevated levels of C3 breakdown products (C3i), which were found in 14 out of 18 tests. The test results returned gradually to normal as symptoms subsided in 20-40 days, but 2 patients still showed abnormalities at 40 days despite the disappearance of symptoms. It is concluded that free immune complexes appear in the circulation during the early stages of acute sarcoidosis and gradually disappear as symptoms subside.

Ingestion of tellurium (0.2 g/day) by rats resulted in the so-called ‘black’ brain caused by the presence of the dark tellurium particles localized in the numerous lipofucsin granules in the cytoplasm of the neurons throughout the brain. The tellurium was identified in the organelles by energy dispersive X-ray spectrometry analysis, and this was correlated with light and electron microscopy examination, to permit morphological interpretation of the succession of pathogenetic events. Tellurium is a known mitochondrial marker and it was thus possible to identify this localization in the early stages of intoxication, both in membrane-bound bodies and eventually in lipofucsin granules. The conclusions are that tellurium given in sufficient amounts causes cerebral lipofucsinosis in the rat, and that the degeneration of mitochondria results in the formation of lipofucsin.

INTRODUCTION THE problem of chronic respiratory disease in chickens has become recognized as a major economic factor in the commercial production of poultry in all areas of the United States. Since its first description and preliminary isolation in 1942 by Delaplane and Stuart (1943) at Rhode Island, this disease has since been observed and isolated from affected poultry in virtually every production area. No accurate data as to absolute economic losses sustained are available; but estimates in the industry indicate an aggregate loss of approximately $100 million per annum for the country as a whole. Obviously, damage of this magnitude calls for a concerted approach to the alleviation of the loss and ultimately complete control of the disease. Continuing his early work in the isolation of the infectious agent, Delaplane (1948) noted that the pathogen was cross-communicable to turkeys and induced a sinusitis-like syndrome. Prier, Sutherland and Beamer (1948) also …

A micro high performance liquid chromatography assay is reported for the measurement of tolazoline in newborn infants. Pharmacokinetic data are presented for a single infant receiving tolazoline therapy. Tolazoline and the internal standard, clonidine, are extracted from alkaline serum into butylchloride/isopropanol (95/5). The organic layer is then back extracted with 50 mM phosphoric acid. A portion of the phosphoric acid layer is injected onto a 15-cm CN-bonded phase column. A mobile phase consisting of acetonitrile and phosphate buffer (pH 3) is used to elute tolazoline and the internal standard in less than 5 min. The effluent is monitored with a fixed wavelength detector at 214 nm. Using 50 microliters of serum, concentrations as low as 0.25 mg/L can be routinely determined with a coefficient of variation (CV) of 7.2%. However, when a 100-microliters sample is used, and the injection volume increased, a concentration of 0.05 mg/L can be routinely monitored with a CV of 1.2%. Interference from other drugs that are often used concurrently with tolazoline therapy was not observed.

This 146-page monograph on the nonoperative aspects of pediatric surgery has been authored by a physician who is Diplomate of both the American Board of Pediatrics and the American Board of Surgery. The book reflects Dr. Owings' excellent training and experience in both fields. The style of this text makes for easy and pleasant reading. The chapters are concise and informative. There is obviously no intent on the author's part to produce a pediatric-surgical text. The book is rather a knowledgeable treatise on the preoperative and postoperative care of the pediatric-surgical patient. There is nothing original in this book, but it is an excellent summary of current pediatric-surgical thought concerning the nonoperative aspects of care in this age group. Dr. Owings wisely stresses the importance of minimal handling of the postoperative neonate. His plea to keep the patient warm and "on the dry side" is also well taken. The chapters