Investigation of the electrical properties of Si₁-×Ge× channel pMOSFETs with high-κ dielectrics

It is now apparent that the continued performance enhancements of silicon metal-oxide-semiconductor field effect transistors (MOSFETs) can no longer be met by scaling alone. High-mobility channel materials such as strained Si1-xGex and Ge are now being seriously considered to maintain the performance requirements specified by the semiconductor industry. In addition, alternative gate dielectric, or high-κ dielectrics, will also be required to meet gate leakage requirements. This work investigates the properties of using strained Si1-xGex or Ge as alternative channel materials for pMOSFETs incorporating hafnium oxide (HfO2) high-κ gate dielectric. Whilst the SiGe pMOSFETs (x = 0.25) exhibited an enhancement in hole mobility (300 K) over comparable silicon control pMOSFETs with sputtered HfO2 dielectric, high Coulomb scattering and surface roughness scattering relating to the dielectric deposition process meant that the effective hole mobilities were degraded with respect to the silicon universal curve. Germanium channel pMOSFETs with halo-doping and HfO2 gate dielectric deposited by atomic layer deposition showed high hole mobilities of 230 cm2V-1s-1 and 480 cm2V-1s-1 at room temperature and 77 K, respectively. Analysis of the off-state current for the Ge pMOSFETs over a range of temperatures indicated that band-to-band tunnelling, gate-induced drain leakage and other defect-assisted leakage mechanisms could all be important. Hole carrier velocity and impact ionisation were also studied in two batches of buried channel SiGe pMOSFET with x = 0.15 and x = 0.36, respectively. SiGe channel pMOSFETs were found to exhibit reduced impact ionisation compared to silicon control devices, which has been attributed to a strain-induced reduction of the density of states in the SiGe conduction and valence bands. Analysis of the hole carrier velocity indicated that pseudomorphic SiGe offered no performance enhancements over Si below 100 nm, possibly due to higher ion implantation damage and strain relaxation of the strained SiGe channel. The results indicate that velocity overshoot effects might not provide the performance improvements at short channel lengths that was previously hoped for

Grandmothers’ care practices in areas of high deprivation of Scotland:the potential for health promotion

In many families grandparents play an essential role by providing secondary care for grandchildren. The family is a key setting for promoting children’s health; however, studies describing health initiatives with grandparents are rare. Grandparents could play an important role in promoting health for their grandchildren within their families and communities. The aim of this study was to examine the care practices of grandparents in families living in areas of high deprivation, and to consider the extent to which grandparents could be at the centre of health-promoting initiatives for children. A family practices approach was used to examine care practices within the framework of family resource (assets/capitals) use. In-depth interviews were carried out with grandmothers (n = 15) and mothers (n = 15) living in areas of high deprivation in Scotland. The results are presented as three economies of family living—political, moral and emotional. Grandparent care was described as a form of social capital, central to the wellbeing of the families, and enabled parents to access education and employment. Grandparent care was supported through families’ ability to access cultural amenities and green space (political). Grandparents’ care practices were described as either being responsible or fun (moral). Love appeared to be at the centre of grandparents’ care (emotional). The strengths and weaknesses of this framework were examined in relation to developing initiatives with grandparents. With further development work, grandparents could be the focus of health initiatives with their grandchildren with the support of appropriate policies and resources within their communities

Fractional quantum Hall states in a Ge quantum well

Measurements of the Hall and dissipative conductivity of a strained Ge quantum well on a SiGe/(001)Si substrate in the quantum Hall regime are reported. We analyse the results in terms of thermally activated quantum tunneling of carriers from one internal edge state to another across saddle points in the long range impurity potential. This shows that the gaps for different filling fractions closely follow the dependence predicted by theory. We also find that the estimates of the separation of the edge states at the saddle are in line with the expectations of an electrostatic model in the lowest spin-polarised Landau level (LL), but not in the spin-reversed LL where the density of quasiparticle states is not high enough to accommodate the carriers required

Loss of Atrx Affects Trophoblast Development and the Pattern of X-Inactivation in Extraembryonic Tissues

ATRX is an X-encoded member of the SNF2 family of ATPase/helicase proteins thought to regulate gene expression by modifying chromatin at target loci. Mutations in ATRX provided the first example of a human genetic disease associated with defects in such proteins. To better understand the role of ATRX in development and the associated abnormalities in the ATR-X (alpha thalassemia mental retardation, X-linked) syndrome, we conditionally inactivated the homolog in mice, Atrx, at the 8- to 16-cell stage of development. The protein, Atrx, was ubiquitously expressed, and male embryos null for Atrx implanted and gastrulated normally but did not survive beyond 9.5 days postcoitus due to a defect in formation of the extraembryonic trophoblast, one of the first terminally differentiated lineages in the developing embryo. Carrier female mice that inherit a maternal null allele should be affected, since the paternal X chromosome is normally inactivated in extraembryonic tissues. Surprisingly, however, some carrier females established a normal placenta and appeared to escape the usual pattern of imprinted X-inactivation in these tissues. Together these findings demonstrate an unexpected, specific, and essential role for Atrx in the development of the murine trophoblast and present an example of escape from imprinted X chromosome inactivation

Heteroepitaxial growth of ferromagnetic MnSb(0001) films on Ge/Si(111) virtual substrates

Molecular beam epitaxial growth of ferromagnetic MnSb(0001) has been achieved on high quality, fully relaxed Ge(111)/Si(111) virtual substrates grown by reduced pressure chemical vapor deposition. The epilayers were characterized using reflection high energy electron diffraction, synchrotron hard X-ray diffraction, X-ray photoemission spectroscopy, and magnetometry. The surface reconstructions, magnetic properties, crystalline quality, and strain relaxation behavior of the MnSb films are similar to those of MnSb grown on GaAs(111). In contrast to GaAs substrates, segregation of substrate atoms through the MnSb film does not occur, and alternative polymorphs of MnSb are absent

A systematic review of grandparents’ influence on grandchildren’s cancer risk factors

Many lifestyle patterns are established when children are young. Research has focused on the potential role of parents as a risk factor for non communicable disease in children, but there is limited investigation of the role of other caregivers, such as grandparents. The aim of this review was to identify and synthesise evidence for any influence grandparents’ care practices may have on their grandchildren’s long term cancer risk factors. A systematic review was carried out with searches across four databases (MEDLINE, Embase, Web of Science, PsycINFO) as well as searches of reference lists and citing articles, and Google Scholar. Search terms were based on six areas of risk that family care could potentially influence–weight, diet, physical activity, tobacco, alcohol and sun exposure. All study designs were included, as were studies that provided an indication of the interaction of grandparents with their grandchildren. Studies were excluded if grandparents were primary caregivers and if children had serious health conditions. Study quality was assessed using National Institute for Health and Care Excellence checklists. Grandparent impact was categorised as beneficial, adverse, mixed or as having no impact. Due to study heterogeneity a meta-analysis was not possible. Qualitative studies underwent a thematic synthesis of their results. Results from all included studies indicated that there was a sufficient evidence base for weight, diet, physical activity and tobacco studies to draw conclusions about grandparents’ influence. One study examined alcohol and no studies examined sun exposure. Evidence indicated that, overall, grandparents had an adverse impact on their grandchildren’s cancer risk factors. The theoretical work in the included studies was limited. Theoretically underpinned interventions designed to reduce these risk factors must consider grandparents’ role, as well as parents’, and be evaluated robustly to inform the evidence base further

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities