Persistence of full glacial conditions in the central Pacific until 15,000 years ago

The magnitude of atmospheric cooling during the Last Glacial Maximum and the timing of the transition into the current interglacial period remain poorly constrained in tropical regions, partly because of a lack of suitable climate records. Glacial moraines provide a method of reconstructing past temperatures, but they are relatively rare in the tropics. Here we present a reconstruction of atmospheric temperatures in the central Pacific during the last deglaciation on the basis of cosmogenic ^3He ages of moraines and numerical modelling of the ice cap on Mauna Kea volcano, Hawaii—the only highland in the central Pacific on which moraines that formed during the last glacial period are preserved. Our reconstruction indicates that the Last Glacial Maximum occurred between 19,000 and 16,000 years ago in this region and that temperatures at high elevations were about 7 °C lower than today during this interval. Glacial retreat began about 16,000 years ago, but temperatures were still about 6.5 °C lower than today until 15,000 years ago. When combined with estimates of sea surface temperatures in the central Pacific Ocean, our reconstruction indicates that the lapse rate during the Last Glacial Maximum was higher than at present, which is consistent with the proposal that the atmosphere was drier at that time. Furthermore, the persistence of full glacial conditions until 15,000 years ago is consistent with the relatively late and abrupt transition to warmer temperatures in Greenland5, indicating that there may have been an atmospheric teleconnection between the central Pacific and North Atlantic regions during the last deglaciation

Seasonally stable temperature gradients through supraglacial debris in the Everest region of Nepal, Central Himalaya

Rock debris covers about 30% of glacier ablation areas in the Central Himalaya and modifies the impact of atmospheric conditions on mass balance. The thermal properties of supraglacial debris are diurnally variable but remain poorly constrained for monsoon-influenced glaciers over the timescale of the ablation season. We measured vertical debris profile temperatures at 12 sites on four glaciers in the Everest region with debris thickness ranging from 0.08–2.8 m. Typically, the length of the ice ablation season beneath supraglacial debris was 160 days (15 May to 22 October)—a month longer than the monsoon season. Debris temperature gradients were approximately linear (r2 > 0.83), measured as –40°C m–1 where debris was up to 0.1 m thick, –20°C m–1 for debris 0.1–0.5 m thick, and –4°C m–1 for debris greater than 0.5 m thick. Our results demonstrate that the influence of supraglacial debris on the temperature of the underlying ice surface, and therefore melt, is stable at a seasonal timescale and can be estimated from near-surface temperature. These results have the potential to greatly improve the representation of ablation in calculations of debris-covered glacier mass balance and projections of their response to climate change.Peer reviewe

Biallelic inherited SCN8A variants, a rare cause of SCN8A‐related developmental and epileptic encephalopathy

ObjectiveMonoallelic de novo gain‐of‐function variants in the voltage‐gated sodium channel SCN8A are one of the recurrent causes of severe developmental and epileptic encephalopathy (DEE). In addition, a small number of de novo or inherited monoallelic loss‐of‐function variants have been found in patients with intellectual disability, autism spectrum disorder, or movement disorders. Inherited monoallelic variants causing either gain or loss‐of‐function are also associated with less severe conditions such as benign familial infantile seizures and isolated movement disorders. In all three categories, the affected individuals are heterozygous for a SCN8A variant in combination with a wild‐type allele. In the present study, we describe two unusual families with severely affected individuals who inherited biallelic variants of SCN8A.MethodsWe identified two families with biallelic SCN8A variants by diagnostic gene panel sequencing. Functional analysis of the variants was performed using voltage clamp recordings from transfected ND7/23 cells.ResultsWe identified three probands from two unrelated families with DEE due to biallelic SCN8A variants. Each parent of an affected individual carried a single heterozygous SCN8A variant and exhibited mild cognitive impairment without seizures. In both families, functional analysis demonstrated segregation of one allele with complete loss‐of‐function, and one allele with altered biophysical properties consistent with partial loss‐of‐function.SignificanceThese studies demonstrate that SCN8A DEE may, in rare cases, result from inheritance of two variants, both of which exhibit reduced channel activity. In these families, heterozygosity for the dominant variants results in less severe disease than biallelic inheritance of two variant alleles. The clinical consequences of variants with partial and complete loss of SCN8A function are variable and likely to be influenced by genetic background.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153117/1/epi16371_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153117/2/epi16371.pd

The ClinGen Epilepsy Gene Curation Expert Panel—Bridging the divide between clinical domain knowledge and formal gene curation criteria

The field of epilepsy genetics is advancing rapidly and epilepsy is emerging as a frequent indication for diagnostic genetic testing. Within the larger ClinGen framework, the ClinGen Epilepsy Gene Curation Expert Panel is tasked with connecting two increasingly separate fields: the domain of traditional clinical epileptology, with its own established language and classification criteria, and the rapidly evolving area of diagnostic genetic testing that adheres to formal criteria for gene and variant curation. We identify critical components unique to the epilepsy gene curation effort, including: (a) precise phenotype definitions within existing disease and phenotype ontologies; (b) consideration of when epilepsy should be curated as a distinct disease entity; (c) strategies for gene selection; and (d) emerging rules for evaluating functional models for seizure disorders. Given that de novo variants play a prominent role in many of the epilepsies, sufficient genetic evidence is often awarded early in the curation process. Therefore, the emphasis of gene curation is frequently shifted toward an iterative precuration process to better capture phenotypic associations. We demonstrate that within the spectrum of neurodevelopmental disorders, gene curation for epilepsy-associated genes is feasible and suggest epilepsy-specific conventions, laying the groundwork for a curation process of all major epilepsy-associated genes

The novel sodium channel modulator GS‐458967 (GS967) is an effective treatment in a mouse model of SCN8A encephalopathy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144249/1/epi14196.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144249/2/epi14196-sup-0001-SupInfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144249/3/epi14196_am.pd

Percutaneous & Mini Invasive Achilles tendon repair

Rupture of the Achilles tendon is a considerable cause of morbidity with reduced function following injury. Recent studies have shown little difference in outcome between the techniques of open and non-operative treatment using an early active rehabilitation programme. Meta-analyses have shown that non-operative management has increased risk of re-rupture whereas surgical intervention has risks of complications related to the wound and iatrogenic nerve injury. Minimally invasive surgery has been adopted as a way of reducing infections rates and wound breakdown however avoiding iatrogenic nerve injury must be considered. We discuss the techniques and outcomes of percutaneous and minimally invasive repairs of the Achilles tendon

Twenty-first century glacier slowdown driven by mass loss in High Mountain Asia

International audienc