Construction of the Views oN Infant Sleep (VNIS) Questionnaire

Parents' beliefs about infant sleep behaviour vary over time and across cultures. No validated instrument exists to understand parents' pre- and postnatal views on infant sleep behaviours, which may influence their caregiving decisions. The Views oN Infant Sleep Questionnaire (VNIS) will be a tool to assess parents' beliefs in order to facilitate tailored perinatal care, increase the reliability of postnatal self-report measures, allow for cross-cultural comparisons, and provide a baseline for researchers to use in longitudinal studies. We recruited an online sample of 971 female participants who were resident in the United Kingdom, at least 28 weeks pregnant, and at least 18 years of age. The initial questionnaire consisted of 31 questions about infant independence, night-waking, infant feeding, touch, and safety, and items were rated on a 5-point Likert scale. The item pool was reduced to 12 using principal component analysis and a structure was found for the three components “Closeness”, “Independence”, and “Night-waking”. Overall, these results suggest that the VNIS can provide a brief scale to measure different aspects of individuals' beliefs about infant sleep. In further research the VNIS needs to be validated with a confirmatory factor analysis in another sample, and to be tested as a cross-cultural instrument

The motor development of orphaned children with and without HIV: Pilot exploration of foster care and residential placement

<p>Abstract</p> <p>Background</p> <p>The AIDS epidemic has lead to an increase in orphaned children who need residential care. It is known that HIV leads to delayed motor development. However, the impact of place of residence on motor function has not been investigated in the South African context. The aim of the study was therefore to establish if children in institutionalised settings performed better or worse in terms of gross motor function than their counterparts in foster care. A secondary objective was to compare the performance of children with HIV in these two settings with those of children who were HIV negative.</p> <p>Methods</p> <p>Forty-four children both with and without HIV, were recruited from institutions and foster care families in Cape Town. The Peabody Development Motor Scale (PDMS II) was used to calculate the total motor quotient (TMQ) at baseline and six months later. Comparisons of TMQ were made between residential settings and between children with and without HIV.</p> <p>Results</p> <p>Twenty-one children were infected with HIV and were significantly delayed compared to their healthy counterparts. Antiretroviral therapy was well managed among the group but did not appear to result in restoration of TMQ to normal over the study period. HIV status and place of residence emerged as a predictor of TMQ with children in residential care performing better than their counterparts in foster care. All children showed improvement over the six months of study.</p> <p>Conclusions</p> <p>Foster parents were well supported administratively in the community by social welfare services but their children might have lacked stimulation in comparison to those in institutional settings. This could have been due to a lack of resources and knowledge regarding child development. The assumption that foster homes provide a better alternative to institutions may not be correct in a resource poor community and needs to be examined further.</p

Enrolling adolescents in HIV vaccine trials: reflections on legal complexities from South Africa

<p>Abstract</p> <p>Background</p> <p>South Africa is likely to be the first country in the world to host an adolescent HIV vaccine trial. Adolescents may be enrolled in late 2007. In the development and review of adolescent HIV vaccine trial protocols there are many complexities to consider, and much work to be done if these important trials are to become a reality.</p> <p>Discussion</p> <p>This article sets out essential requirements for the lawful conduct of adolescent research in South Africa including compliance with consent requirements, child protection laws, and processes for the ethical and regulatory approval of research.</p> <p>Summary</p> <p>This article outlines likely complexities for researchers and research ethics committees, including determining that trial interventions meet current risk standards for child research. Explicit recommendations are made for role-players in other jurisdictions who may also be planning such trials. This article concludes with concrete steps for implementing these important trials in South Africa and other jurisdictions, including planning for consent processes; delineating privacy rights; compiling information necessary for ethics committees to assess risks to child participants; training trial site staff to recognize when disclosures trig mandatory reporting response; networking among relevant ethics commitees; and lobbying the National Regulatory Authority for guidance.</p

Changes in malaria morbidity and mortality in Mpumalanga Province, South Africa (2001- 2009): a retrospective study

<p>Abstract</p> <p>Background</p> <p>Malaria remains a serious epidemic threat in Mpumalanga Province. In order to appropriately target interventions to achieve substantial reduction in the burden of malaria and ultimately eliminate the disease, there is a need to track progress of malaria control efforts by assessing the time trends and evaluating the impact of current control interventions. This study aimed to assess the changes in the burden of malaria in Mpumalanga Province during the past eight malaria seasons (2001/02 to 2008/09) and whether indoor residual spraying (IRS) and climate variability had an effect on these changes.</p> <p>Methods</p> <p>This is a descriptive retrospective study based on the analysis of secondary malaria surveillance data (cases and deaths) in Mpumalanga Province. Data were extracted from the Integrated Malaria Information System. Time series model (Autoregressive Integrated Moving Average) was used to assess the association between climate and malaria.</p> <p>Results</p> <p>Within the study period, a total of 35,191 cases and 164 deaths due to malaria were notified in Mpumalanga Province. There was a significant decrease in the incidence of malaria from 385 in 2001/02 to 50 cases per 100,000 population in 2008/09 (<it>P </it>< 0.005). The incidence and case fatality (CFR) rates for the study period were 134 cases per 100,000 and 0.54%, respectively. Mortality due to malaria was lower in infants and children (CFR < 0.5%) and higher in those >65 years, with the mean CFR of 2.1% as compared to the national target of 0.5%. A distinct seasonal transmission pattern was found to be significantly related to changes in rainfall patterns (<it>P </it>= 0.007). A notable decline in malaria case notification was observed following apparent scale-up of IRS coverage from 2006/07 to 2008/09 malaria seasons.</p> <p>Conclusions</p> <p>Mpumalanga Province has achieved the goal of reducing malaria morbidity and mortality by over 70%, partly as a result of scale-up of IRS intervention in combination with other control strategies. These results highlight the need to continue with IRS together with other control strategies until interruption in local malaria transmission is completely achieved. However, the goal to eliminate malaria as a public health problem requires efforts to be directed towards the control of imported malaria cases; development of strategies to interrupt local transmission; and maintaining high quality surveillance and reporting system.</p

Glycine Inhibitory Dysfunction Turns Touch into Pain through PKCgamma Interneurons

Dynamic mechanical allodynia is a widespread and intractable symptom of neuropathic pain for which there is a lack of effective therapy. During tactile allodynia, activation of the sensory fibers which normally detect touch elicits pain. Here we provide a new behavioral investigation into the dynamic component of tactile allodynia that developed in rats after segmental removal of glycine inhibition. Using in vivo electrophysiological recordings, we show that in this condition innocuous mechanical stimuli could activate superficial dorsal horn nociceptive specific neurons. These neurons do not normally respond to touch. We anatomically show that the activation was mediated through a local circuit involving neurons expressing the gamma isoform of protein kinase C (PKCγ). Selective inhibition of PKCγ as well as selective blockade of glutamate NMDA receptors in the superficial dorsal horn prevented both activation of the circuit and allodynia. Thus, our data demonstrates that a normally inactive circuit in the dorsal horn can be recruited to convert touch into pain. It also provides evidence that glycine inhibitory dysfunction gates tactile input to nociceptive specific neurons through PKCγ-dependent activation of a local, excitatory, NMDA receptor-dependent, circuit. As a consequence of these findings, we suggest that pharmacological inhibition of PKCγ might provide a new tool for alleviating allodynia in the clinical setting

Integrative mRNA profiling comparing cultured primary cells with clinical samples reveals PLK1 and C20orf20 as therapeutic targets in cutaneous squamous cell carcinoma

This work was funded by DebRA, the dystrophic epidermolysis bullosa research association (http:// www.debra.org.uk

Global urban environmental change drives adaptation in white clover.

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta