The international Inherited Neuropathy Consortium (INC) was created with the goal of obtaining much needed natural history data for patients with Charcot-Marie-Tooth (CMT) disease. We analysed ...clinical and genetic data from patients in the INC to determine the distribution of CMT subtypes and the clinical impairment associated with them.
We analysed data from 1652 patients evaluated at 13 INC centres. The distribution of CMT subtypes and pathogenic genetic mutations were determined. The disease burden of all the mutations was assessed by the CMT Neuropathy Score (CMTNS) and CMT Examination Score (CMTES).
997 of the 1652 patients (60.4%) received a genetic diagnosis. The most common CMT subtypes were CMT1A/PMP22 duplication, CMT1X/GJB1 mutation, CMT2A/MFN2 mutation, CMT1B/MPZ mutation, and hereditary neuropathy with liability to pressure palsy/PMP22 deletion. These five subtypes of CMT accounted for 89.2% of all genetically confirmed mutations. Mean CMTNS for some but not all subtypes were similar to those previously reported.
Our findings confirm that large numbers of patients with a representative variety of CMT subtypes have been enrolled and that the frequency of achieving a molecular diagnosis and distribution of the CMT subtypes reflects those previously reported. Measures of severity are similar, though not identical, to results from smaller series. This study confirms that it is possible to assess patients in a uniform way between international centres, which is critical for the planned natural history study and future clinical trials. These data will provide a representative baseline for longitudinal studies of CMT.
ID number NCT01193075.
The basaltic aquifers of the Upper Bhima River basin in southern India are heavily utilized for small-scale agriculture but face increasing demand-related pressures along with uncertainty associated ...with climate change impacts. To evaluate likely groundwater resource impacts over the coming decades, a regional groundwater flow model for the basin was developed. Model predictions associated with different climate change and abstraction scenarios indicate that the continuation of current rates of abstraction would lead to significant groundwater overdraft, with groundwater elevations predicted to fall by -6 m over the next three decades. Groundwater elevations can however be stabilized, but would require 20-30% of the mean surface water discharge from the basin to be recharged to groundwater, along with reductions in pumping (5-10%) brought about by improved water efficiency practices and/or shifts towards lower-water use crops. Modest reductions in pumping alone cannot stabilize groundwater levels; targeted conjunctive use and improved water use efficiency are also needed.
Grasses are noted for an absence of toxic secondary metabolites. However, some grass-associated fungi are known for their production of numerous secondary compounds, which serve important functions ...such as plant competition and resistance to biotic and abiotic stresses. Cohabitation of certain fungi with grasses has developed into specific mutualistic associations. The fungi of concern belong to a relatively small group of species within the Clavicipitaceae. This group of fungi shares a common feature in being endophytically associated with grasses as obligate biotrophic symbionts. Specific attention is given to two related genera
Epichloë and their anamorphic
Neotyphodium relatives. The association of these fungi with grasses results in the accumulation of several classes of fungal metabolites that serve as relief mechanisms to biotic and abiotic stresses. These include drought tolerance, resistance to vertebrate and invertebrate pests, resistance to fungal diseases, and tolerance to poor soil conditions. Resistance to multiple stresses can occur simultaneously within the same symbiotum. The resulting resistance to multiple stresses, along with inter- and intra-specific competitive advantage suggests the potential for utilizing novel fungal endophytes new host combinations for stress resistance in naturally infected grasses as well as for resistance to specific agronomic and ecological conditions and soil remediation.
Abstract
Recent borehole seismic deployments conducted along the Baribis Fault in northwestern Java reveal that it may be active. In this study, we exploit these data to locate proximal earthquakes ...using a relative relocation technique, estimate their moment magnitudes using a spectral fitting method and compute their focal mechanisms via waveform inversion. We observe that seismicity in the eastern part of the fault is significantly higher than in the west, where a previous GPS study of the region south of Jakarta demonstrated the existence of high compression rates. These observations imply that the western Baribis Fault is locked, and that neighbouring areas, including southern Jakarta and its surroundings, may be highly vulnerable to future sizeable earthquakes when accumulated elastic strain energy is eventually released during fault rupture. Significantly, the current generation of Indonesia’s national hazard maps have not considered seismicity along the Baribis Fault. Our new results therefore call for an urgent reappraisal of the seismic hazard in northwestern Java that carefully takes into account the Baribis Fault and its earthquake potential, particularly in light of its proximity to Jakarta, a megacity that lies at the heart of one of the most densely populated islands in the world.
The non-collinear mixing technique is applied for detection and characterization of closed cracks. The method is based on the nonlinear interaction of two shear waves generated with an oblique ...incidence, which leads to the scattering of a longitudinal wave. A Finite Element model is used to demonstrate its application to a closed crack. Contact acoustic nonlinearity is modeled using unilateral contact law with Coulomb׳s friction. The method is shown to be effective and promising when applied to a closed crack. Scattering of the longitudinal wave also enables us to image the crack, giving its position and size.
•Application of the non-colinear mixing technique to a closed crack.•Finite Element Modeling of non-colineear mixing technique.•The crack is modeled by an interface of unilateral contact with Coulomb׳s friction.•The mechanisms of the scattering of the longitudinal wave are explained.•Different parameters (position of sources, angle of incidence) are investigated.
Neurodevelopmental disorders are multi-faceted and can lead to intellectual disability, autism spectrum disorder and language impairment. Mutations in the Forkhead box FOXP1 gene have been linked to ...all these disorders, suggesting that it may play a central role in various cognitive and social processes. To understand the role of Foxp1 in the context of neurodevelopment leading to alterations in cognition and behaviour, we generated mice with a brain-specific Foxp1 deletion (Nestin-Cre(Foxp1-/-)mice). The mutant mice were viable and allowed for the first time the analysis of pre- and postnatal neurodevelopmental phenotypes, which included a pronounced disruption of the developing striatum and more subtle alterations in the hippocampus. More detailed analysis in the CA1 region revealed abnormal neuronal morphogenesis that was associated with reduced excitability and an imbalance of excitatory to inhibitory input in CA1 hippocampal neurons in Nestin-Cre(Foxp1-/-) mice. Foxp1 ablation was also associated with various cognitive and social deficits, providing new insights into its behavioural importance.
Background Long COVID potentially increases healthcare utilisation and costs. However, its impact on the NHS remains to be determined. Methods This study aims to assess the healthcare utilisation of ...individuals with long COVID. With the approval of NHS England, we conducted a matched cohort study using primary and secondary care data via OpenSAFELY, a platform for analysing anonymous electronic health records. The long COVID exposure group, defined by diagnostic codes, was matched with five comparators without long COVID between Nov 2020 and Jan 2023. We compared their total healthcare utilisation from GP consultations, prescriptions, hospital admissions, A&E visits, and outpatient appointments. Healthcare utilisation and costs were evaluated using a two-part model adjusting for covariates. Using a difference-in-difference model, we also compared healthcare utilisation after long COVID with pre-pandemic records. Results We identified 52,988 individuals with a long COVID diagnosis, matched to 264,867 comparators without a diagnosis. In the 12 months post-diagnosis, there was strong evidence that those with long COVID were more likely to use healthcare resources (OR: 8.29, 95% CI: 7.74-8.87), and have 49% more healthcare utilisation (RR: 1.49, 95% CI: 1.48-1.51). Our model estimated that the long COVID group had 30 healthcare visits per year (predicted mean: 29.23, 95% CI: 28.58-29.92), compared to 16 in the comparator group (predicted mean visits: 16.04, 95% CI: 15.73-16.36). Individuals with long COVID were more likely to have non-zero healthcare expenditures (OR = 7.66, 95% CI = 7.20-8.15), with costs being 44% higher than the comparator group (cost ratio = 1.44, 95% CI: 1.39-1.50). The long COVID group costs approximately pounds sterling2500 per person per year (predicted mean cost: pounds sterling2562.50, 95% CI: pounds sterling2335.60-pounds sterling2819.22), and the comparator group costs pounds sterling1500 (predicted mean cost: pounds sterling1527.43, 95% CI: pounds sterling1404.33-1664.45). Historically, individuals with long COVID utilised healthcare resources more frequently, but their average healthcare utilisation increased more after being diagnosed with long COVID, compared to the comparator group. Conclusions Long COVID increases healthcare utilisation and costs. Public health policies should allocate more resources towards preventing, treating, and supporting individuals with long COVID. Keywords: Long COVID, Electronic health records, Facilities and services utilization, Health care costs
Characterization of language in naturalistic settings in autism spectrum disorder has been lacking, particularly at young ages, but such information is important for parents, teachers, and clinicians ...to better support language development in real-world settings. Factors contributing to this lack of clarity include conflicting definitions of language abilities, use of non-naturalistic standardized assessments, and restricted samples. The current study examined one of the largest datasets of naturalistic language samples in toddlers with autism spectrum disorder, and language delay and typically developing contrast groups at age 3. A range of indices including length of phrase, grammatical markings, and social use of language was assayed during a naturalistic observation of a parent–child play session. In contrast to historical estimates, results indicated only 3.7% of children with autism spectrum disorder used no words, and 34% were minimally verbal. Children with autism spectrum disorder and language delay exhibited similar usage of grammatical markings, although both were reduced compared to typically developing children. The greatest difference between autism spectrum disorder and language delay groups was the quantity of social language. Overall, findings highlight a range of language deficits in autism spectrum disorder, but also illustrate that the most severe level of impairments is not as common in naturalistic settings as previously estimated by standardized assessments.
The relative paucity of recent post‐subduction environments globally has meant that, so far, little is known about tectonic processes that occur during and after subduction termination, as previously ...convergent tectonic plates adjust to the new stress regime. The region of Southeast Asia that now encompasses northern Borneo has been host to two sequential episodes of subduction—both now terminated—since the mid‐Paleogene. It is expected that these processes will have left signatures in the fabric of the upper mantle, which are manifest in the form of seismic anisotropy. We investigate the evidence for, and alignment of, anisotropic fabrics by measuring the splitting of a family of teleseismic shear phases. These observations provide a measure of the orientation of the effective anisotropic elastic tensor, in the form of the orientation of the fast shear‐wave polarization, ϕ, and add constraints on the strength of the anisotropic fabric, in the form of the delay time, δt. We observe two principal trends across northern Borneo that appear to be confined to the lithosphere. These patterns are likely related to tectonic processes associated with subduction, continental collision, and oceanic basin formation, events that can exert primary influence on the formation of post‐subduction settings.
Plain Language Summary
This study is concerned with understanding what happens to the upper 200 km of the Earth when subduction—the process by which one plate pushes beneath another and sinks into the Earth's interior—stops. We measure a property of the rock in the upper 200 km called seismic anisotropy, which tells us how fast earthquake waves move when traveling or polarized in one direction compared to another. Seismic anisotropy can inform us about both large‐scale plate tectonic events in recent geological history (10s of millions of years) and present‐day deformation. Northern Borneo has undergone two phases of active subduction followed by termination in the last 25 million years, making it one of the few places on Earth where we can explore this important stage of the subduction cycle. We find that tectonic compression and extension events related to termination and post‐subduction processes have left strong imprints in the upper 100 km of the Earth, leaving little‐to‐no remnants of signals we might have expected to observe from the active phase of subduction.
Key Points
New catalog of shear‐wave splitting measurements from a dense network in post‐subduction setting
Two trends in the fast orientations, corresponding to fabric generated by subduction termination and post‐subduction processes
Seismic anisotropy is limited to the lithosphere beneath northern Borneo, with no strong signal in radial anisotropy of simple asthenospheric flow
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