The relation of environmental factors to failure in treatment -

Thesis (M.S.)--Boston University, 1948. This item was digitized by the Internet Archive

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)

Map Collections and Map Librarianship in Australia

published or submitted for publicatio

Hydrogeology and water quality of significant sand and gravel aquifers in parts of Androscoggin, Cumberland, Franklin, Kennebec, Lincoln, Oxford, Sagadahoc, and Somerset Counties, Maine; sand and gravel aquifer maps 10, 11, 16, 17, and 32

Maine Geological Survey, Open-File Report 85-82a. Accompanies 1:24000 Significant Aquifer Mapshttps://digitalmaine.com/mgs_publications/1173/thumbnail.jp

Hydrogeology and water quality of significant sand and gravel aquifers in parts of Androscoggin, Cumberland, Franklin, Kennebec, Lincoln, Oxford, Sagadahoc, and Somerset Counties, Maine; sand and gravel aquifer maps 10, 11, 16, 17, and 32

Maine Geological Survey, Open-File Report 85-82a. Accompanies 1:24000 Significant Aquifer Mapshttps://digitalmaine.com/mgs_publications/1173/thumbnail.jp

Prevention of recurrence of venous ulceration: randomised controlled trial of class 2 and class 3 elastic compression

ObjectiveTo compare venous ulcer recurrence and compliance with two strengths of compression hosiery.MethodsThis study was a randomized controlled trial with a 5-year follow-up. The setting was the leg ulcer clinics of a teaching and a district general hospital in Scotland, United Kingdom. Patients were 300 outpatients with recently healed venous ulcers, with no significant arterial disease, rheumatoid disease, or diabetes mellitus. Interventions were fitting and supply of class 2 or class 3 compression hosiery. Four-monthly refitting by trained orthotists and surveillance by specialist nurses were performed. The main outcome measures were recurrence of leg ulceration and compliance with treatment.ResultsThirty-six percent (107/300) of patients had recurrent leg ulceration by 5 years. Recurrence occurred in 59 (39%) of 151 class 2 elastic compression cases and in 48 (32%) of class 3 compression cases. One hundred six patients did not comply with their randomized compression class, 63 (42%) in class 3 and 43 (28%) in class 2. The difference in recurrence is not statistically significant, but our estimate of the effectiveness of class 3 hosiery is diluted by the lower compliance rate in this group. Restricted ankle movement and four or more previous ulcers were associated with a higher risk of recurrence.ConclusionsThere was no evidence of a difference in recurrence rates at the classic level of significance (5%), but the lowest recurrence rates were seen in people who wore the highest degree of compression. Therefore, patients should wear the highest level of compression that is comfortable

A factorial, randomized trial of pentoxifylline or placebo, four-layer or single-layer compression, and knitted viscose or hydrocolloid dressings for venous ulcers

ObjectivesWe evaluated the effectiveness of pentoxifylline, knitted viscose or hydrocolloid dressings, and single-layer or four-layer bandaging for venous ulceration.MethodA factorial randomized controlled trial with 24-week follow-up was conducted in leg ulcer clinics in Scotland with blinded allocation to pentoxifylline (1200 mg) or placebo, knitted viscose or hydrocolloid dressings, and single-layer or four-layer bandages. The study enrolled 245 adults with venous ulcers. The main outcome measure was time to complete healing. Secondary outcomes included proportions healed, withdrawals, and adverse events. Analysis was by intention to treat.ResultsThere was no evidence of interaction between the drug, bandages, and dressings. Pentoxifylline was associated with nonsignificant increased ulcer healing (62% vs 53%; P = .21). Four-layer bandages were associated with significantly higher healing rates (67% vs 49%; P = .009). There was no difference in healing between knitted viscose and hydrocolloid dressings (58% and 57%; P = .88). Cox regression models increased the significance of the pentoxifylline effect (relative risk of healing, 1.4; 95% confidence interval, 1.0 to 2.0).ConclusionsPentoxifylline increased the proportion healing compared with placebo to the same extent as shown in recent systematic reviews, although this finding was only statistically significant when a secondary adjusted analysis was conducted. Four-layer bandaging produced higher healing rates than single-layer bandaging. There was no difference in time to healing between knitted viscose and hydrocolloid dressings