The spatio-temporal structure of the Lateglacial to early Holocene transition reconstructed from the pollen record of Lake Suigetsu and its precise correlation with other key global archives:Implications for palaeoclimatology and archaeology

Leads, lags, or synchronies in climatic events among different regions are key to understanding mechanisms of climate change, as they provide insights into the causal linkages among components of the climate system. The well-studied transition from the Lateglacial to early Holocene (ca. 16–10 ka) contains several abrupt climatic shifts, making this period ideal for assessing the spatio-temporal structure of climate change. However, comparisons of timings of past climatic events among regions often remain hypothetical because site-specific age scales are not necessarily synchronised to each other. Here we present new pollen data (n = 510) and mean annual temperature reconstruction from the annually laminated sediments of Lake Suigetsu, Japan. Suigetsu's 14C dataset is an integral component of the IntCal20 radiocarbon calibration model, in which the absolute age scale is established to the highest standard. Its exceptionally high-precision chronology, along with recent advances in cosmogenic isotope studies of ice cores, enables temporally coherent comparisons among Suigetsu, Greenland, and other key proxy records across regions. We show that the onsets of the Lateglacial cold reversal (equivalent to GS-1/Younger Dryas) and the Holocene were synchronous between East Asia and the North Atlantic, whereas the Lateglacial interstadial (equivalent to GI-1/Bølling-Allerød) started ca. two centuries earlier in East Asia than in the North Atlantic. Bimodal migration (or ‘jump’) of the westerly jet between north and south of the Tibetan plateau and Himalayas may have operated as a threshold system responsible for the abruptness of the change in East and South (and possibly also West) Asia. That threshold in Asia and another major threshold in the North Atlantic, associated with switching on/off of the Atlantic meridional overturning circulation (AMOC), were crossed at different times, producing a multi-centennial asynchrony of abrupt changes, as well as a disparity of climatic modes among regions during the transitional phases. Such disparity may have disturbed zonal circulation and generated unstable climate during transitions. The intervening periods with stable climate, on the other hand, coincided with the beginnings of sedentary life and agriculture, implying that these new lifestyles and technologies were not rational unless climate was stable and thus, to a certain extent, predictable

Efficacy and safety of valganciclovir in patients with symptomatic congenital cytomegalovirus disease Study Protocol Clinical Trial (SPIRIT Compliant)

Background: Congenital cytomegalovirus (CMV) disease, a common mother-to-child infection, can lead to neurological sequelae. Some clinical trials have shown that oral valganciclovir (VGCV) can improve hearing and neurodevelopmental impairment in infants with congenital CMV disease. However, VGCV has neither been approved in Japan nor other countries as a treatment for this disease by the government health insurance. Methods: This study is a non-randomized, prospective, open-label, multicenter, single-arm clinical trial and will include subjects meeting the following criteria: confirmation of positive CMV-DNA amplification in urine by an in vitro diagnostic test within 21 days of age; congenital CMV disease with one or more central nervous system disorders-microcephaly, hydrocephalus or ventricular enlargement, periventricular calcification, cortical hypoplasia or white matter injury, retinal choroiditis, and abnormal auditory brainstem response (ABR); and infants within 2 months of age with a gestational age >= 32 weeks at birth and weighing >= 1800 g at the time of registration. Subjects will be orally administered 16 mg/kg VGCV twice daily for 6 months. The target number of cases for enrollment between February 3, 2020 and July 31, 2021 is 25. Primary endpoint is the change in whole blood CMV loads before and after 6 months of treatment. The important secondary endpoint is the change in ABR (both best and total ear hearing assessments) before and after 6 months of treatment. The safety endpoints are adverse events and drug side effects. Discussion: To the best of our knowledge, this multicenter, open-label, single-arm study will be the first well-designed clinical trial to evaluate the efficacy of oral VGCV in infants with congenital CMV diseases. The findings will reveal the efficacy and safety of oral VGCV treatments and enable the approval of oral VGCV as a treatment for infants with congenital CMV disease by the government health insurance of Japan

Evaluation of bovine viral diarrhoea virus control strategies in dairy herds in Hokkaido, Japan, using stochastic modelling

Bovine viral diarrhoea virus (BVDV) infection in cattle can result in growth retardation, reduced milk production, reproductive disorders and death. Persistently infected animals are the primary source of infection. In Hokkaido, Japan, all cattle entering shared pastures in summer are vaccinated before movement for disease control. Additionally, these cattle may be tested for BVDV and culled if positive. However, the effectiveness of this control strategy aiming to reduce the number of BVDV-infected animals has not been assessed. The aim of this study was to evaluate the effectiveness of various test-and-cull and/or vaccination strategies on BVDV control in dairy farms in two districts of Hokkaido, Nemuro and Hiyama. A stochastic model was developed to compare the different control strategies over a 10-year period. The model was individual-based and simulated disease dynamics both within and between herds. Parameters included in the model were obtained from the literature, the Hokkaido government and the Japanese Ministry of Agriculture, Forestry and Fisheries. Nine different scenarios were compared as follows: no control, test-and-cull strategies based on antigen testing of either calves or only cattle entering common pastures, vaccination of all adult cattle or only cattle entering shared pastures and combinations thereof. The results indicate that current strategies for BVDV control in Hokkaido slightly reduced the number of BVDV-infected animals; however, alternative strategies such as testing all calves and culling any positives or vaccinating all susceptible adult animals dramatically reduced those. To our knowledge, this is the first report regarding the comparison of the effectiveness between the current strategies in Hokkaido and the alternative strategies for BVDV control measures

Oral Valganciclovir Therapy in Infants Aged ≤2 Months with Congenital Cytomegalovirus Disease: A Multicenter, Single-Arm, Open-Label Clinical Trial in Japan

Our aims were to determine the clinical impact of oral valganciclovir (VGCV) in infants aged ≤2 months with congenital cytomegalovirus (CMV) disease and evaluate the efficacy of VGCV when initiated beyond the neonatal period. The multicenter, single-arm, open-label clinical trial was conducted in Japan. Twenty-five infants aged ≤2 months with congenital CMV disease involving the central nervous system were enrolled and treated with VGCV for 6 months. The primary endpoint was the change in the whole blood CMV load before and after treatment. The secondary endpoint was the change in the auditory brainstem response (ABR) before and after treatment. Changes in ABR were assessed between the younger and older age groups (≤ and >30 days at treatment initiation). Of the 25 patients, one was excluded owing to epilepsy before VGCV administration. The median change in the CMV DNA level in whole blood was −246.0 IU/mL. The best ear and total ear assessments based on ABR were categorized as (improved + unchanged) after treatment for 100% and 93.8%, respectively. No differences in hearing efficacy were observed between the younger and older age groups. Oral VGCV is a potential therapeutic option for treating infants aged ≤2 months with congenital CMV disease

A case of autoimmune pulmonary alveolar proteinosis responding to oral statin therapy

There is no approved drug treatment for autoimmune pulmonary alveolar proteinosis (APAP), although traditionally requires complex treatments such as whole lung lavage (WLL). We herein report on a 67-year-old man diagnosed with APAP. Treatment with atorvastatin (5 mg daily) resulted in significant improvement in symptoms, lung function, and computed tomography findings, with enhanced oxygenation, although serum anti-GM-CSF antibody levels remained elevated. This case suggests that the remission observed in this case could potentially be attributed to a direct effect of atorvastatin within the pulmonary alveoli. Statins may be considered as one of the treatment options for APAP