Hypothermia for perinatal asphyxial encephalopathy. A Swiss survey of opinion, practice and cerebral investigations

BACKGROUND: Perinatal asphyxial encephalopathy occurs in 1-per 1000 live births and is associated with high mortality and morbidity. Therapeutic hypothermia increases intact survival and improves neurodevelopmental outcome in survivors.AIMS: To evaluate (i) the opinion and practice of therapeutic hypothermia as a therapy for moderate to severe perinatal asphyxial encephalopathy amongst Swiss neonatologists and paediatric intensive care specialists, (ii) the current clinical management of infants with perinatal asphyxial encephalopathy and (iii) the need for a national perinatal asphyxia and therapeutic hypothermia registry.METHODS: Two web-based questionnaires were sent to 18 senior staff physicians within the Swiss Neonatal Network.RESULTS: Therapeutic hypothermia was considered effective by all responders, however only 11 of 18 units provided therapeutic hypothermia. Cooling was initiated during transfer and performed passively in 82% of centres with a target rectal temperature of 33-34 degrees C. Most units ventilated infants with perinatal asphyxial encephalopathy if clinically indicated and 73% of responders gave analgesia routinely to cooled infants. Neuromonitoring included continuous amplitude integrated EEG (aEEG) and EEG. Neuroimaging included cranial ultrasound (cUS), magnetic resonance imaging (MRI) and computed tomography (CT). Sixty-seven percent of units treating infants with perinatal asphyxial encephalopathy performed MRI routinely. All heads of departments questioned indicated that a "Swiss National Asphyxia and Cooling Registry" is needed.CONCLUSIONS: In Switzerland, access to therapeutic hypothermia is widespread and Swiss neonatologists believe that therapeutic hypothermia for perinatal asphyxia is effective. National cooling protocols are needed for the management of infants with perinatal asphyxial encephalopathy in order to ensure safe cooling, appropriate monitoring, imaging and follow-up assessment. A national registry is needed to collect data on diagnosis, treatment, adverse events and outcome

Designing theoretically-informed implementation interventions

Clinical and health services research is continually producing new findings that may contribute to effective and efficient patient care. However, the transfer of research findings into practice is unpredictable and can be a slow and haphazard process. Ideally, the choice of implementation strategies would be based upon evidence from randomised controlled trials or systematic reviews of a given implementation strategy. Unfortunately, reviews of implementation strategies consistently report effectiveness some, but not all of the time; possible causes of this variation are seldom reported or measured by the investigators in the original studies. Thus, any attempts to extrapolate from study settings to the real world are hampered by a lack of understanding of the effects of key elements of individuals, interventions, and the settings in which they were trialled. The explicit use of theory offers a way of addressing these issues and has a number of advantages, such as providing: a generalisable framework within which to represent the dimensions that implementation studies address, a process by which to inform the development and delivery of interventions, a guide when evaluating, and a way to allow for an exploration of potential causal mechanisms. However, the use of theory in designing implementation interventions is methodologically challenging for a number of reasons, including choosing between theories and faithfully translating theoretical constructs into interventions. The explicit use of theory offers potential advantages in terms of facilitating a better understanding of the generalisability and replicability of implementation interventions. However, this is a relatively unexplored methodological area

Effects of cash transfers on Children's health and social protection in Sub-Saharan Africa: differences in outcomes based on orphan status and household assets

BACKGROUND: Unconditional and conditional cash transfer programmes (UCT and CCT) show potential to improve the well-being of orphans and other children made vulnerable by HIV/AIDS (OVC). We address the gap in current understanding about the extent to which household-based cash transfers differentially impact individual children’s outcomes, according to risk or protective factors such as orphan status and household assets. METHODS: Data were obtained from a cluster-randomised controlled trial in eastern Zimbabwe, with random assignment to three study arms – UCT, CCT or control. The sample included 5,331 children ages 6-17 from 1,697 households. Generalized linear mixed models were specified to predict OVC health vulnerability (child chronic illness and disability) and social protection (birth registration and 90% school attendance). Models included child-level risk factors (age, orphan status); household risk factors (adults with chronic illnesses and disabilities, greater household size); and household protective factors (including asset-holding). Interactions were systematically tested. RESULTS: Orphan status was associated with decreased likelihood for birth registration, and paternal orphans and children for whom both parents’ survival status was unknown were less likely to attend school. In the UCT arm, paternal orphans fared better in likelihood of birth registration compared with non-paternal orphans. Effects of study arms on outcomes were not moderated by any other risk or protective factors. High household asset-holding was associated with decreased likelihood of child’s chronic illness and increased birth registration and school attendance, but household assets did not moderate the effects of cash transfers on risk or protective factors. CONCLUSION: Orphaned children are at higher risk for poor social protection outcomes even when cared for in family-based settings. UCT and CCT each produced direct effects on children’s social protection which are not moderated by other child- and household-level risk factors, but orphans are less likely to attend school or obtain birth registration. The effects of UCT and CCT are not moderated by asset-holding, but greater household assets predict greater social protection outcomes. Intervention efforts need to focus on ameliorating the additional risk burden carried by orphaned children. These efforts might include caregiver education, and additional incentives based on efforts made specifically for orphaned children

A Compromise between Neutrino Masses and Collider Signatures in the Type-II Seesaw Model

A natural extension of the standard $SU(2)_{\rm L} \times U(1)_{\rm Y}$ gauge model to accommodate massive neutrinos is to introduce one Higgs triplet and three right-handed Majorana neutrinos, leading to a $6\times 6$ neutrino mass matrix which contains three $3\times 3$ sub-matrices $M_{\rm L}$, $M_{\rm D}$ and $M_{\rm R}$. We show that three light Majorana neutrinos (i.e., the mass eigenstates of $\nu_e$, $\nu_\mu$ and $\nu_\tau$) are exactly massless in this model, if and only if $M_{\rm L} = M_{\rm D} M_{\rm R}^{-1} M_{\rm D}^T$ exactly holds. This no-go theorem implies that small but non-vanishing neutrino masses may result from a significant but incomplete cancellation between $M_{\rm L}$ and $M_{\rm D} M_{\rm R}^{-1} M_{\rm D}^T$ terms in the Type-II seesaw formula, provided three right-handed Majorana neutrinos are of ${\cal O}(1)$ TeV and experimentally detectable at the LHC. We propose three simple Type-II seesaw scenarios with the $A_4 \times U(1)_{\rm X}$ flavor symmetry to interpret the observed neutrino mass spectrum and neutrino mixing pattern. Such a TeV-scale neutrino model can be tested in two complementary ways: (1) searching for possible collider signatures of lepton number violation induced by the right-handed Majorana neutrinos and doubly-charged Higgs particles; and (2) searching for possible consequences of unitarity violation of the $3\times 3$ neutrino mixing matrix in the future long-baseline neutrino oscillation experiments.Comment: RevTeX 19 pages, no figure

Recurrent Modification of a Conserved Cis-Regulatory Element Underlies Fruit Fly Pigmentation Diversity

The development of morphological traits occurs through the collective action of networks of genes connected at the level of gene expression. As any node in a network may be a target of evolutionary change, the recurrent targeting of the same node would indicate that the path of evolution is biased for the relevant trait and network. Although examples of parallel evolution have implicated recurrent modification of the same gene and cis-regulatory element (CRE), little is known about the mutational and molecular paths of parallel CRE evolution. In Drosophila melanogaster fruit flies, the Bric-à-brac (Bab) transcription factors control the development of a suite of sexually dimorphic traits on the posterior abdomen. Female-specific Bab expression is regulated by the dimorphic element, a CRE that possesses direct inputs from body plan (ABD-B) and sex-determination (DSX) transcription factors. Here, we find that the recurrent evolutionary modification of this CRE underlies both intraspecific and interspecific variation in female pigmentation in the melanogaster species group. By reconstructing the sequence and regulatory activity of the ancestral Drosophila melanogaster dimorphic element, we demonstrate that a handful of mutations were sufficient to create independent CRE alleles with differing activities. Moreover, intraspecific and interspecific dimorphic element evolution proceeded with little to no alterations to the known body plan and sex-determination regulatory linkages. Collectively, our findings represent an example where the paths of evolution appear biased to a specific CRE, and drastic changes in function were accompanied by deep conservation of key regulatory linkages. © 2013 Rogers et al

Functional Locomotor Consequences of Uneven Forefeet for Trot Symmetry in Individual Riding Horses

ABSTRACT: Left-right symmetrical distal limb conformation can be an important prerequisite for a successful performance, and it is often hypothesized that asymmetric or uneven feet are important enhancing factors for the development of lameness. On a population level, it has been demonstrated that uneven footed horses are retiring earlier from elite level competition, but the biomechanical consequences are not yet known. The objectives of this study were to compare the functional locomotor asymmetries of horses with uneven to those with even feet. Hoof kinetics and distal limb kinematics were collected from horses (n = 34) at trot. Dorsal hoof wall angle was used to classify horses as even or uneven (1.5° difference between forefeet respectively) and individual feet as flat (55°). Functional kinetic parameters were compared between even and uneven forefeet using MANOVA followed by ANOVA. The relative influences of differences in hoof angle between the forefeet and of absolute hoof angle on functional parameters were analysed using multiple regression analysis (P<0.05). In horses with uneven feet, the side with the flatter foot showed a significantly larger maximal horizontal braking and vertical ground reaction force, a larger vertical fetlock displacement and a suppler fetlock spring. The foot with a steeper hoof angle was linearly correlated with an earlier braking-propulsion transition. The conformational differences between both forefeet were more important for loading characteristics than the individual foot conformation of each individual horse. The differences in vertical force and braking force between uneven forefeet could imply either an asymmetrical loading pattern without a pathological component or a subclinical lameness as a result of a pathological development in the steeper foot

A search for the decay modes B+/- to h+/- tau l

We present a search for the lepton flavor violating decay modes B+/- to h+/- tau l (h= K,pi; l= e,mu) using the BaBar data sample, which corresponds to 472 million BBbar pairs. The search uses events where one B meson is fully reconstructed in one of several hadronic final states. Using the momenta of the reconstructed B, h, and l candidates, we are able to fully determine the tau four-momentum. The resulting tau candidate mass is our main discriminant against combinatorial background. We see no evidence for B+/- to h+/- tau l decays and set a 90% confidence level upper limit on each branching fraction at the level of a few times 10^-5.Comment: 15 pages, 7 figures, submitted to Phys. Rev.

Search for Second-Generation Scalar Leptoquarks in ppˉ\bm{p \bar{p}} Collisions at s\sqrt{s}=1.96 TeV

Results on a search for pair production of second generation scalar leptoquark in $p \bar{p}$ collisions at $\sqrt{s}$=1.96 TeV are reported. The data analyzed were collected by the CDF detector during the 2002-2003 Tevatron Run II and correspond to an integrated luminosity of 198 pb$^{-1}$. Leptoquarks (LQ) are sought through their decay into (charged) leptons and quarks, with final state signatures represented by two muons and jets and one muon, large transverse missing energy and jets. We observe no evidence for $LQ$ production and derive 95% C.L. upper limits on the $LQ$ production cross sections as well as lower limits on their mass as a function of $\beta$, where $\beta$ is the branching fraction for $LQ \to \mu q$.Comment: 9 pages (3 author list) 5 figure