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BackgroundActive follow-up of chronic hepatitis C notifications to promote linkage to care is a promising strategy to support elimination.AimThis pilot study in Victoria, Australia, explored if the Department of Health could follow-up on hepatitis C cases through their diagnosing clinicians, to assess and support linkage to care and complete data missing from the notification.MethodsFor notifications received between 1 September 2021 and 31 March 2022 of unspecified hepatitis C cases (i.e. acquired > 24 months ago or of unknown duration), contact with diagnosing clinicians was attempted. Data were collected on risk exposures, clinical and demographic characteristics and follow-up care (i.e. HCV RNA test; referral or ascertainment of previous negative testing or treatment history). Reasons for unsuccessful doctor contact and gaps in care provision were investigated. Advice to clinicians on care and resources for clinical support were given on demand.ResultsOf 513 cases where information was sought, this was able to be obtained for 356 (69.4%). Reasons for unsuccessful contact included incomplete contact details or difficulties getting in touch across three attempts, particularly for hospital diagnoses. Among the 356 cases, 307 (86.2%) had received follow-up care. Patient-management resources were requested by 100 of 286 contacted diagnosing clinicians.ConclusionsMost doctors successfully contacted had provided follow-up care. Missing contact information and the time taken to reach clinicians significantly impeded the feasibility of the intervention. Enhancing system automation, such as integration of laboratory results, could improve completeness of notifications and support further linkage to care where needed.

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and heterologous immunization approaches implemented worldwide for booster doses call for diversified vaccine portfolios. GRAd-COV2 is a gorilla adenovirus-based COVID-19 vaccine candidate encoding prefusion-stabilized spike. The safety and immunogenicity of GRAd-COV2 is evaluated in a dose- and regimen-finding phase 2 trial (COVITAR study, ClinicalTrials.gov: NCT04791423) whereby 917 eligible participants are randomized to receive a single intramuscular GRAd-COV2 administration followed by placebo, or two vaccine injections, or two doses of placebo, spaced over 3 weeks. Here, we report that GRAd-COV2 is well tolerated and induces robust immune responses after a single immunization; a second administration increases binding and neutralizing antibody titers. Potent, variant of concern (VOC) cross-reactive spike-specific T cell response peaks after the first dose and is characterized by high frequencies of CD8s. T cells maintain immediate effector functions and high proliferative potential over time. Thus, GRAd vector is a valuable platform for genetic vaccine development, especially when robust CD8 response is needed.

Sediment records from deep-drilling projects such as those carried out by the International Continental Scientific Drilling Program are often tens to hundreds of meters in length. To ensure the complete recovery of a stratigraphic section, a basin is usually cored multiple times in adjacent holes so that gaps between sequential cores, poorly recovered sections, or intervals affected by disturbance can be bridged or replaced with sediments from another hole. Stratigraphic correlation, the alignment of stratigraphically-equivalent horizons in cores from different holes in a common-depth scale, and splice generation, the integration of the most-representative core sections into a composite-stratigraphic section, are essential steps in this process to both evaluate and synthesize the recovered-sediment record and focus the scientific analyses. However, these undertakings can be complex and are inherently subjective, making the need for the development of a single robust stratigraphic section early in the project critical to its success. Despite this, the steps between core recovery and on-splice data generation are rarely published in sufficient detail to allow reconstruction, or refinement, of the composited record at a later date. To increase the transparency of how the composite record is created, and to provide a template for future projects, we detail the step-by-step approaches and decisions involved in generating the composite-depth scale and complete-stratigraphic splice following recovery of sediments from Lake Junín, Peru. We first explain the details and nuances of different drilling-depth scales before describing how we integrated different physical property records to generate the composite-depth scale and complete-stratigraphic splice. Here, we show that due to the complex stratigraphy in the Lake Junín sediments, high-resolution line-scan images of the cores offer millimeter-scale precision for construction of the primary-stratigraphic splice at

At present, the commercially dominant and rapidly expanding PV-device technology is based on the passivated emitter and rear cell (PERC) design developed at UNSW. However, this technology has been found to suffer from a carrier-induced degradation commonly referred to as ‘light- and elevated temperature-induced degradation’ (LeTID) and can result in up to 16% relative performance losses. LeTID was recently shown to occur in almost every type of silicon wafer, independent of the doping material. Even though the degradation mechanism is known to recover under normal operation conditions, it is a lengthy process that drastically affects the energy yield, stability and, ultimately, the levelized cost of electricity (LCOE) of installed systems. Despite the joint effort of many research groups, the root cause of the degradation is still unknown. Here, we provide an overview of the existing literature and describe key LeTID characteristics and how these have led to the development of various theories of the underlying mechanism. Further, given the continuously appearing and strong evidence of hydrogen involvement in LeTID, many mitigation methods concerning hydrogenation have been suggested. We discuss such reported methods, bearing in mind crucial consumer necessities in terms of sustained cell performance and minimised LCOE.

Wiedemann-Steiner syndrome (WSS) is an autosomal dominant disorder caused by monoallelic variants in KMT2A and characterized by intellectual disability and hypertrichosis. We performed a retrospective, multicenter, observational study of 104 individuals with WSS from five continents to characterize the clinical and molecular spectrum of WSS in diverse populations, to identify physical features that may be more prevalent in White versus Black Indigenous People of Color individuals, to delineate genotype-phenotype correlations, to define developmental milestones, to describe the syndrome through adulthood, and to examine clinicians' differential diagnoses. Sixty-nine of the 82 variants (84%) observed in the study were not previously reported in the literature. Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%). The median ages at walking and first words were 20 months and 18 months, respectively. Hypotonia was associated with loss of function (LoF) variants, and seizures were associated with non-LoF variants. This study identifies genotype-phenotype correlations as well as race-facial feature associations in an ethnically diverse cohort, and accurately defines developmental trajectories, medical comorbidities, and long-term outcomes in individuals with WSS.

Attrition refers to students leaving programmes of study before completion. This is an important topic area; there is a current global shortage of nurses, and it is widely reported that nursing is in crisis. Nurse education in the United Kingdom has changed substantially in the past fifty years, gradually moving from work-based apprentice style training to an ‘all graduate entry’ profession. There is a plethora of literature reporting attrition both in the UK and worldwide. It is clear that regardless of the education model, attrition from pre-registration programmes is a long-standing problem which has attracted much attention. The educative process of learning to be a nurse can be likened to a ‘rite of passage’, or perhaps a series of rites of passage. Rites of passage were first articulated by anthropologists, van Gennep and Turner. Van Gennep and Turner argued that as people make ‘transitions’, often via ‘rites of passage’ they pass through an in-between phase described as ‘liminal’. This paper explores aspects of liminality in nurse education and examines the potential relationship with attrition. The paper concludes by suggesting that although liminality could be considered a risk factor for attrition, exploitation of the concept may offer opportunities to enhance learning.

Spermatogenesis-associated 5 like 1 (SPATA5L1) represents an orphan gene encoding a protein of unknown function. We report 28 bi-allelic variants in SPATA5L1 associated with sensorineural hearing loss in 47 individuals from 28 (26 unrelated) families. In addition, 25/47 affected individuals (53%) presented with microcephaly, developmental delay/intellectual disability, cerebral palsy, and/or epilepsy. Modeling indicated damaging effect of variants on the protein, largely via destabilizing effects on protein domains. Brain imaging revealed diminished cerebral volume, thin corpus callosum, and periventricular leukomalacia, and quantitative volumetry demonstrated significantly diminished white matter volumes in several individuals. Immunofluorescent imaging in rat hippocampal neurons revealed localization of Spata5l1 in neuronal and glial cell nuclei and more prominent expression in neurons. In the rodent inner ear, Spata5l1 is expressed in the neurosensory hair cells and inner ear supporting cells. Transcriptomic analysis performed with fibroblasts from affected individuals was able to distinguish affected from controls by principal components. Analysis of differentially expressed genes and networks suggested a role for SPATA5L1 in cell surface adhesion receptor function, intracellular focal adhesions, and DNA replication and mitosis. Collectively, our results indicate that bi-allelic SPATA5L1 variants lead to a human disease characterized by sensorineural hearing loss (SNHL) with or without a nonprogressive mixed neurodevelopmental phenotype.

Sediment records from deep-drilling projects such as those carried out by the International Continental Scientific Drilling Program are often tens to hundreds of meters in length. To ensure the complete recovery of a stratigraphic section, a basin is usually cored multiple times in adjacent holes so that gaps between sequential cores, poorly recovered sections, or intervals affected by disturbance can be bridged or replaced with sediments from another hole. Stratigraphic correlation, the alignment of stratigraphically-equivalent horizons in cores from different holes in a common-depth scale, and splice generation, the integration of the most-representative core sections into a composite-stratigraphic section, are essential steps in this process to both evaluate and synthesize the recovered-sediment record and focus the scientific analyses. However, these undertakings can be complex and are inherently subjective, making the need for the development of a single robust stratigraphic section early in the project critical to its success. Despite this, the steps between core recovery and on-splice data generation are rarely published in sufficient detail to allow reconstruction, or refinement, of the composited record at a later date. To increase the transparency of how the composite record is created, and to provide a template for future projects, we detail the step-by-step approaches and decisions involved in generating the composite-depth scale and complete-stratigraphic splice following recovery of sediments from Lake Junín, Peru. We first explain the details and nuances of different drilling-depth scales before describing how we integrated different physical property records to generate the composite-depth scale and complete-stratigraphic splice. Here, we show that due to the complex stratigraphy in the Lake Junín sediments, high-resolution line-scan images of the cores offer millimeter-scale precision for construction of the primary-stratigraphic splice at

Asparagine-linked glycosylation 13 homolog (ALG13) encodes a nonredundant, highly conserved, X-linked uridine diphosphate (UDP)-N-acetylglucosaminyltransferase required for the synthesis of lipid linked oligosaccharide precursor and proper N-linked glycosylation. De novo variants in ALG13 underlie a form of early infantile epileptic encephalopathy known as EIEE36, but given its essential role in glycosylation, it is also considered a congenital disorder of glycosylation (CDG), ALG13-CDG. Twenty-four previously reported ALG13-CDG cases had de novo variants, but surprisingly, unlike most forms of CDG, ALG13-CDG did not show the anticipated glycosylation defects, typically detected by altered transferrin glycosylation. Structural homology modeling of two recurrent de novo variants, p.A81T and p.N107S, suggests both are likely to impact the function of ALG13. Using a corresponding ALG13-deficient yeast strain, we show that expressing yeast ALG13 with either of the highly conserved hotspot variants rescues the observed growth defect, but not its glycosylation abnormality. We present molecular and clinical data on 29 previously unreported individuals with de novo variants in ALG13. This more than doubles the number of known cases. A key finding is that a vast majority of the individuals presents with West syndrome, a feature shared with other CDG types. Among these, the initial epileptic spasms best responded to adrenocorticotropic hormone or prednisolone, while clobazam and felbamate showed promise for continued epilepsy treatment. A ketogenic diet seems to play an important role in the treatment of these individuals.Copyright © 2020 SSIEM

In this article, we investigate the extent of lifetime degradation attributed to light- and elevated-temperature-induced degradation (LeTID) in p-type multicrystalline silicon wafers passivated with different configurations of hydrogenated silicon nitride (SiNx:H) and aluminum oxide (AlOx:H). We also demonstrate a significant difference between AlOx:H layers grown by atomic layer deposition (ALD) and plasma-enhanced chemical vapor deposition (PECVD) with respect to the extent of LeTID. When ALD AlOx:H is placed underneath a PECVD SiNx:H layer, as used in a passivated emitter and rear solar cell, a lower extent of LeTID is observed compared with the case when a single PECVD SiNx:H layer is used. On the other hand, the LeTID extent is significantly increased when an ALD AlOx:H is grown on top of the PECVD SiNx:H film. Remarkably, when a PECVD AlOx:H is used underneath the PECVD SiNx:H film, an increase in the LeTID extent is observed. Building on our current understanding of LeTID, we explain these results with the role of ALD AlOx:H in impeding the hydrogen diffusion from the dielectric stack into the c-Si bulk, while PECVD AlOx:H seems to act as an additional hydrogen source. These observations support the hypothesis that hydrogen is playing a key role in LeTID and provide solar cell manufacturers with a new method to reduce LeTID in their solar cells.

Asparagine-linked glycosylation 13 homolog (ALG13) encodes a nonredundant, highly conserved, X-linked uridine diphosphate (UDP)-N-acetylglucosaminyltransferase required for the synthesis of lipid linked oligosaccharide precursor and proper N-linked glycosylation. De novo variants in ALG13 underlie a form of early infantile epileptic encephalopathy known as EIEE36, but given its essential role in glycosylation, it is also considered a congenital disorder of glycosylation (CDG), ALG13-CDG. Twenty-four previously reported ALG13-CDG cases had de novo variants, but surprisingly, unlike most forms of CDG, ALG13-CDG did not show the anticipated glycosylation defects, typically detected by altered transferrin glycosylation. Structural homology modeling of two recurrent de novo variants, p.A81T and p.N107S, suggests both are likely to impact the function of ALG13. Using a corresponding ALG13-deficient yeast strain, we show that expressing yeast ALG13 with either of the highly conserved hotspot variants rescues the observed growth defect, but not its glycosylation abnormality. We present molecular and clinical data on 29 previously unreported individuals with de novo variants in ALG13. This more than doubles the number of known cases. A key finding is that a vast majority of the individuals presents with West syndrome, a feature shared with other CDG types. Among these, the initial epileptic spasms best responded to adrenocorticotropic hormone or prednisolone, while clobazam and felbamate showed promise for continued epilepsy treatment. A ketogenic diet seems to play an important role in the treatment of these individuals.