Chemical weathering and provenance evolution of Holocene–Recent sediments from the Western Indus Shelf, Northern Arabian Sea inferred from physical and mineralogical properties

We present a multi-proxy mineral record based on X-ray diffraction and diffuse reflectance spectrophotometry analysis for two cores from the western Indus Shelf in order to reconstruct changing weathering intensities, sediment transport, and provenance variations since 13 ka. Core Indus-10 is located northwest of the Indus Canyon and exhibits fluctuations in smectite/(illite + chlorite) ratios that correlate with monsoon intensity. Higher smectite/(illite + chlorite) and lower illite crystallinity, normally associated with stronger weathering, peaked during the Early–Mid Holocene, the period of maximum summer monsoon. Hematite/goethite and magnetic susceptibility do not show clear co-variation, although they both increase at Indus-10 after 10 ka, as the monsoon weakened. At Indus-23, located on a clinoform just west of the canyon, hematite/goethite increased during a period of monsoon strengthening from 10 to 8 ka, consistent with increased seasonality and/or reworking of sediment deposited prior to or during the glacial maximum. After 2 ka terrigenous sediment accumulation rates in both cores increased together with redness and hematite/goethite, which we attribute to widespread cultivation of the floodplain triggering reworking, especially after 200 years ago. Over Holocene timescales sediment composition and mineralogy in two localities on the high-energy shelf were controlled by varying degrees of reworking, as well as climatically modulated chemical weathering

Resting state connectivity and cognitive performance in adults with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Cognitive impairment is an inevitable feature of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), affecting executive function, attention and processing speed from an early stage. Impairment is associated with structural markers such as lacunes, but associations with functional connectivity have not yet been reported. Twenty-two adults with genetically-confirmed CADASIL (11 male; aged 49.8 ± 11.2 years) underwent functional magnetic resonance imaging at rest. Intrinsic attentional/executive networks were identified using group independent components analysis. A linear regression model tested voxel-wise associations between cognitive measures and component spatial maps, and Pearson correlations were performed with mean intra-component connectivity z-scores. Two frontoparietal components were associated with cognitive performance. Voxel-wise analyses showed an association between one component cluster and processing speed (left middle temporal gyrus; peak −48, −18, −14; ZE = 5.65, pFWEcorr = 0.001). Mean connectivity in both components correlated with processing speed (r = 0.45, p = 0.043; r = 0.56, p = 0.008). Mean connectivity in one component correlated with faster Trailmaking B minus A time (r = −0.77, p < 0.001) and better executive performance (r = 0.56, p = 0.011). This preliminary study provides evidence for associations between cognitive performance and attentional network connectivity in CADASIL. Functional connectivity may be a useful biomarker of cognitive performance in this population

United States Pharmacopeia-National Formulary

The paper explains the workings of the USP-NF as they impact pharmaceutical excipients. The USP-NF is published by the Unites States Pharmacopeia Convention, Inc. which is unusual for a national pharmacopeia in that it is not part of government, but is an independent non-governmental organization (NGO) operating as a not-for-profit corporation. The USP-NF is a member of the Pharmacopoeial Discussion Group (PDG) along with the European Pharmacopoeia (Ph.Eur) and Japanese Pharmacopoeia (JP)

An alternative approach to adjustment of the level of incorporation of boundary lubricants to accommodate changes in granule or blend characteristics

A method is proposed whereby the determination of the level of incorporation of a boundary lubricant is based on the surface area of the blend or granulation and the shape of the lubricant particles. This is a more logical approach to the lubrication of blends and granulations for the manufacture of solid oral dosage forms than the percentage by weight approach that has traditionally been used. Equations are provided to allow the adjustment of the level of incorporation of the boundary lubricant based on the variation in the surface area of the granulation or blend. This method has a potential application in the manufacture of solid oral dosage forms by both batch and continuous processing. The concept of lubricant coverage is relevant to the development of solid oral dosage forms using Quality by Design principles, since certain changes in the granulation or blend characteristics on scale-up would be compensated for, and the use of grade bracketing strategies would be facilitated

Complete genome sequence of Salmonella enterica serovar Typhimurium U288

Salmonella enterica serovar Typhimurium U288 has firmly established itself within the United Kingdom pig production industry. The prevalence of this highly pathogenic multidrug-resistant serovar at such a critical point in the food chain is therefore of great concern. To enhance our understanding of this microorganism, whole-genome and plasmid sequencing was performed

The complete plasmid sequences of Salmonella enterica serovar Typhimurium U288.

Salmonella enterica Serovar Typhimurium U288 is an emerging pathogen of pigs. The strain contains three plasmids of diverse origin that encode traits that are of concern for food security and safety, these include antibiotic resistant determinants, an array of functions that can modify cell physiology and permit genetic mobility. At 148,711 bp, pSTU288-1 appears to be a hybrid plasmid containing a conglomerate of genes found in pSLT of S. Typhimurium LT2, coupled with a mosaic of horizontally-acquired elements. Class I integron containing gene cassettes conferring resistance against clinically important antibiotics and compounds are present in pSTU288-1. A curious feature of the plasmid involves the deletion of two genes encoded in the Salmonella plasmid virulence operon (spvR and spvA) following the insertion of a tnpA IS26-like element coupled to a blaTEM gene. The spv operon is considered to be a major plasmid-encoded Salmonella virulence factor that is essential for the intracellular lifecycle. The loss of the positive regulator SpvR may impact on the pathogenesis of S. Typhimurium U288. A second 11,067 bp plasmid designated pSTU288-2 contains further antibiotic resistance determinants, as well as replication and mobilization genes. Finally, a small 4675 bp plasmid pSTU288-3 was identified containing mobilization genes and a pleD-like G-G-D/E-E-F conserved domain protein that modulate intracellular levels of cyclic di-GMP, and are associated with motile to sessile transitions in growth

Coagulation and fibrinolytic activity of tenecteplase and alteplase in acute ischemic stroke

Background and Purpose—We compared the fibrinolytic activity of tenecteplase and alteplase in patients with acute ischemic stroke, and explored the association between hypofibrinogenaemia and intracerebral hemorrhage. Methods—Venous blood samples from a subgroup of participants in the Alteplase–Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST) study were obtained at pretreatment, 3 to 12 hours, and 24±3 hours post-intravenous thrombolysis for analyses of plasminogen, plasminogen activator inhibitor-1, D-dimer, factor V, fibrinogen, and fibrin(ogen) degradation products, in addition to routine coagulation assays. Related sample Wilcoxon signed-rank tests were used to test the within-group changes, and independent Mann–Whitney tests for between-group differences. Results—Thirty patients were included (alteplase=14 and tenecteplase=16) with similar baseline demographics. Compared with baseline, alteplase caused significant hypofibrinogenaemia (P=0.002), prolonged prothrombin time (P=0.011), hypoplasminogenaemia (P=0.001), and lower factor V (P=0.002) at 3 to 12 hours after administration with persistent hypofibrinogenaemia at 24 hours (P=0.011), whereas only minor hypoplasminogenaemia (P=0.029) was seen in the tenecteplase group. Tenecteplase consumed less plasminogen (P<0.001) and fibrinogen (P=0.002) compared with alteplase. Conclusions—In patients with acute ischemic stroke, alteplase 0.9 mg/kg caused significant disruption of the fibrinolytic system, whereas tenecteplase 0.25 mg/kg did not, consistent with the trend toward lower intracerebral hemorrhage incidence with tenecteplase in the ATTEST study

North Atlantic ecosystem sensitivity to Holocene shifts in Meridional Overturning Circulation

Rapid changes in North Atlantic climate over the last millennia were driven by coupled sea surface/atmospheric processes and rates of deep-water formation. Holocene climate changes, however, remain poorly documented due to a lack of high-resolution paleoclimate records, and their impacts on marine ecosystems remain unknown. We present a 4500 years absolute-dated sea surface radiocarbon record from northeast Atlantic cold-water corals. In contrast to the current view that surface ocean changes occurred on millennial-scale cycles, our record shows more abrupt changes in surface circulation. Changes were centered at 3.4, 2.7, 1.7 and 1.2 ky BP, and associated with atmospheric re-organization. Solar irradiance may have influenced these anomalies, but changes in North Atlantic deep-water convection are likely to have amplified these signals. Critically, we provide the first evidence that these perturbations in Atlantic Meridional Overturning Circulation led to the decline of cold-water coral ecosystems from 1.2 to ~ 0.1 ky BP

Evaluation of a group acceptance commitment therapy intervention for people with knee or hip osteoarthritis: a pilot randomized controlled trial

Objectives: The aim was to evaluate an Acceptance Commitment Therapy (ACT) intervention for people with knee or hip osteoarthritis; a related aim was to compare treatment effects from Rasch-transformed and standard scales. Methods: Participants were recruited from a research database and outpatient rheumatology and orthopaedic clinics at two hospitals. Eligible participants were randomly allocated to either intervention or usual care. Intervention comprised six-sessions of group ACT. Outcomes were assessed two and four months after randomisation. Rasch-transformed and standard self-report measures were compared. Qualitative interviews also explored the acceptability of the intervention. Results: Of 8 people assessed for eligibility, 31 (36%) were randomised. The main reason for non-randomisation was that participants received surgery. Of the 16 participants randomised to intervention, 64% completed ≥50% of the scheduled group sessions. Follow-up data was complete for 84% participants at two months and 68% at four months. Outcome analysis demonstrated important differences between the Rasch-transformed and standard scales. There were significant differences between the groups in pain. Qualitative interviews with 7 participants suggested the intervention was acceptable. Conclusions: ACT for osteoarthritis is likely to be an acceptable treatment option for people with osteoarthritis. Progress to a definitive trial is warranted. Rasch-transformed outcome scales are preferable in clinical trials where possible