Emerging prenatal genetic tests : developing a health technology assessment (HTA) framework for informed decision-making

Delphi Process In preparation for the first Delphi exercise, a list of questions was produced from the academic literature, webbased sources and interviews with experts. These questions were structured into broad dimensions and a draft questionnaire piloted. A final list of 73 questions formed the basis of the first Delphi survey. Participants were asked to grade the perceived importance of each question for inclusion in HTA reports on new prenatal genetic tests (4 = Essential; 3 = Desirable, but not essential; 2 = Useful but should not be required; 1 = Of little/ no importance; 0 = I have no basis for judgement). Secondly, they were asked to indicate whether a question should be addressed during test development or whether the question could be addressed later once the technology is ready for implementation. Finally, Panel members were encouraged to identify any other questions which appeared to be missing from the initial list. For copy of questionnaire, see Annex 1: Delphi Round 1 Questionnaire. Respondents were also asked to provide personal details to give some indication of their HTA experience and specialist expertise. Analysis of responses demonstrated that SAFE Delphi panel members represent a highly experienced, multidisciplinary international group of experts with the knowledge required to define which key questions should be addressed in HTA reports on new prenatal genetic tests. Delphi Responses Responses were received from 77/90 (86%) of Panel members. These were analysed with a cut-off of 75% (±3%) applied as an indicator of Panel consensus for all questions. Thus, any question which three out of four respondents rated as essential or desirable was retained, whilst those not achieving this level of agreement were provisionally excluded. In addition, mean scores were also calculated (excluding 0 = I have no basis for judgement) for each question. A mean score >3.25 ± 0.05 was taken as an indication that the Panel had identified a particular question as being of the highest priority to address in HTA

A review of evidence on non-invasive prenatal diagnosis (NIPD) : tests for fetal RHD genotype

This report concentrates on three main areas. First and foremost, we set the background context for RhD NIPD in prenatal care. While the methodology chapter describes how the literature review was carried out and how additional information was collected, the second chapter provides an overview of the key issues associated with pregnancy of RhD negative women. We present background information based on publications from 1997 to 2006 which describe the genetic condition and its prevalence (RhD negativity) in populations, as well as the frequency of cases of sensitisation and HDN (haemolytic disease of the newborn). We also discuss current service provision for RhD negative women in a number of European countries and look at how the NIPD test might be set within current service contexts

Models for providing improved care in residential care homes: a thematic literature review

This Annotated Bibliography is one output from a review of the available research evidence to support improved care in residential care homes as the needs of older people intensify. Key findings The review identified extremely little published evidence on residential care homes; the research base is almost exclusively related to provision of care in nursing homes. Much of this research is from the US or other non-UK sources. Although it could be argued that some findings are generalisable to the UK residential care context, a systematic process is required to identify which. The literature often makes no distinction between nursing and residential homes; use of generic terms such as ‘care home’ should be avoided. There is considerable international debate in the quality improvement literature about the relationship between quality of care and quality of life in nursing and residential homes. Measures of social care, as well as clinical care, are needed. The centrality of the resident’s voice in measuring quality of life must be recognised. Ethnic minority residents are almost entirely absent from the quality improvement literature. Some clinical areas, internationally identified as key in terms of quality e.g. palliative care, are absent in the general nursing and residential home quality improvement literature. Others such as mental health (dementia and depression), diabetes, and nutrition are present but not fully integrated. Considerable evidence points to a need for better management of medication in nursing homes. Pharmacist medication reviews have shown a positive effect in nursing homes. It is unclear how this evidence might relate to residential care. There is evidence that medical cover for nursing and residential care home residents is suboptimal. Care could be restructured to give a greater scope for proactive and preventive interventions. General practitioners' workload in care homes may be considered against quality-of-care measures. There is US literature on the relationship between nurse staffing and nursing care home quality, with quality measured through clinical-based outcomes for residents and organisational outcomes. Conclusions are difficult to draw however due to inconsistencies in the evidencebase. Hospital admission and early discharge to nursing homes research may not be generalisable to residential care. The quality of inter-institutional transfers and ensuring patient safety across settings is important. To date research has not considered transfer from residential to nursing home care. The literature on district nurse and therapist roles in care homes includes very little research on residential care. Partnership working between district nurses and care home staff appears largely to occur by default at present. There is even less research evidence on therapist input to care homes. Set against the context outlined above, the international literature provides evidence of a number of approaches to care improvement, primarily in nursing homes. These include little discussion of cost-effectiveness other than in telecare. Research is needed in the UK on care improvement in residential homes

Calcium-sensing soluble adenylyl cyclase mediates TNF signal transduction in human neutrophils

Through chemical screening, we identified a pyrazolone that reversibly blocked the activation of phagocyte oxidase (phox) in human neutrophils in response to tumor necrosis factor (TNF) or formylated peptide. The pyrazolone spared activation of phox by phorbol ester or bacteria, bacterial killing, TNF-induced granule exocytosis and phox assembly, and endothelial transmigration. We traced the pyrazolone's mechanism of action to inhibition of TNF-induced intracellular Ca2+ elevations, and identified a nontransmembrane (“soluble”) adenylyl cyclase (sAC) in neutrophils as a Ca2+-sensing source of cAMP. A sAC inhibitor mimicked the pyrazolone's effect on phox. Both compounds blocked TNF-induced activation of Rap1A, a phox-associated guanosine triphosphatase that is regulated by cAMP. Thus, TNF turns on phox through a Ca2+-triggered, sAC-dependent process that may involve activation of Rap1A. This pathway may offer opportunities to suppress oxidative damage during inflammation without blocking antimicrobial function

A Covariant model for the nucleon and the Δ\Delta

The covariant spectator formalism is used to model the nucleon and the $\Delta$(1232) as a system of three constituent quarks with their own electromagnetic structure. The definition of the ``fixed-axis'' polarization states for the diquark emitted from the initial state vertex and absorbed into the final state vertex is discussed. The helicity sum over those states is evaluated and seen to be covariant. Using this approach, all four electromagnetic form factors of the nucleon, together with the {\it magnetic} form factor, $G_M^*$, for the $\gamma N \to \Delta$ transition, can be described using manifestly covariant nucleon and $\Delta$ wave functions with {\it zero} orbital angular momentum $L$, but a successful description of $G_M^*$ near $Q^2=0$ requires the addition of a pion cloud term not included in the class of valence quark models considered here. We also show that the pure $S$-wave model gives electric, $G_E^*$, and coulomb, $G^*_C$, transition form factors that are identically zero, showing that these form factors are sensitive to wave function components with $L>0$.Comment: 20 pages, 5 figures, 2 table

Psychiatric intensive care units: A literature review

Background: Psychiatric Intensive Care Units (PICU) have been part of most inpatient psychiatric services for some time, however information about their functioning and outcome has not previously been collated. Aim: To conduct a systematic literature review to assess the current state of knowledge about such services. Method: A search of electronic databases was undertaken, followed by obtaining additional references from items obtained. Results: Over 50 papers in English containing some empirical data were identified. Most studies were retrospective. Typical PICU patients are: male; younger; single; unemployed; suffering from schizophrenia or mania; from a black Caribbean or African background; legally detained; with a forensic history. The most common reason for admission is for aggression management, and most patients stay a week or less. Evidence of the efficacy of PICU care is very poor. Conclusions: Most research so far has been small scale, and more substantial work using better methodologies is clearly required

New scientific discoveries : plants and fungi

Scientific discovery, including naming new taxa, is important because without a scientific name, a species is invisible to science and the possibilities of researching its ecology, applications and threats, and conserving it, are greatly reduced. We review new scientific discoveries in the plant and fungal kingdoms, based largely on new names of taxa published in 2019 and indexed in the International Plant Names Index and Index Fungorum. Numbers of new species in both kingdoms were similar with 1942 new species of plant published and 1882 species of fungi. However, while >50% of plant species have likely been discovered, >90% of fungi remain unknown. This gulf likely explains the greater number of higher order taxa for fungi published in 2019: three classes, 18 orders, 48 families and 214 genera versus one new family and 87 new genera for plants. We compare the kingdoms in terms of rates of scientific discovery, globally and in different taxonomic groups and geographic areas, and with regard to the use of DNA in discovery. We review species new to science, especially those of interest to humanity as new products, and also by life‐form. We consider where future such discoveries can be expected. We recommend an urgent increase in investment in scientific discovery of plant and fungal species, while they still survive. Priorities include more investment in training taxonomists, in building and equipping collections‐based research centers for them, especially in species‐rich, income‐poor countries where the bulk of species as yet unknown to science are thought to occur

Development of a rhesus monkey lung geometry model and application to particle deposition in comparison to humans

The exposure-dose-response characterization of an inhalation hazard established in an animal species needs to be translated to an equivalent characterization in humans relative to comparable doses or exposure scenarios. Here, the first geometry model of the conducting airways for rhesus monkeys is developed based upon CT images of the conducting airways of a 6-month-old male, rhesus monkey. An algorithm was developed for adding the alveolar region airways using published rhesus morphometric data. The resultant lung geometry model can be used in mechanistic particle or gaseous dosimetry models. Such dosimetry models require estimates of the upper respiratory tract volume of the animal and the functional residual capacity, as well as of the tidal volume and breathing frequency of the animal. The relationship of these variables to rhesus monkeys of differing body weights was established by synthesizing and modeling published data as well as modeling pulmonary function measurements on 121 rhesus control animals. Deposition patterns of particles up to 10 μm in size were examined for endotracheal and and up to 5 μm for spontaneous breathing in infant and young adult monkeys and compared to those for humans. Deposition fraction of respirable size particles was found to be higher in the conducting airways of infant and young adult rhesus monkeys compared to humans. Due to the filtering effect of the conducting airways, pulmonary deposition in rhesus monkeys was lower than that in humans. Future research areas are identified that would either allow replacing assumptions or improving the newly developed lung model