A randomized, controlled trial comparing ganciclovir to ganciclovir plus foscarnet (each at half dose) for preemptive therapy of cytomegalovirus infection in transplant recipients

Forty-eight patients who provided 2 consecutive blood samples that tested positive for cytomegalovirus DNA by polymerase chain reaction (PCR) were randomized to receive either full-dose ganciclovir ( 5 mg/kg intravenously [iv] twice daily) or half-dose ganciclovir (5 mg/kg iv once daily) plus half-dose foscarnet (90 mg/kg iv once daily) for 14 days. In the ganciclovir arm, 17 (71%) of 24 patients reached the primary end point of being CMV negative by PCR within 14 days of initiation of therapy, compared with 12 (50%) of 24 patients in the ganciclovir-plus-foscarnet arm (P = .12). Toxicity was greater in the combination-therapy arm. In patients who failed to reach the primary end point, baseline virus load was 0.77 log(10) higher, the replication rate before therapy was faster (1.5 vs. 2.7 days), and the viral decay rate was slower (2.9 vs. 1.1 days) after therapy. Bivariable logistic regression models identified baseline virus load, bone-marrow transplantation, and doubling time and half-life of decay as the major factors affecting response to therapy within 14 days. This study did not support a synergistic effect of ganciclovir plus foscarnet in vivo

Problems Associated with Making Mechanical Measurements on Water–Ice at Quasistatic and Dynamic Strain Rates

Space penetrators are a potential method of inserting instrumentation onto ice-covered bodies in the solar system. Part of a study to see whether this is feasible involves numerically simulating impact of the penetrator into ice at impact velocities of a few 100 m/s. In order to do this accurately, it is necessary to have a constitutive model for water ice that is valid at the strain rates and temperatures relevant to impact in the Outer Solar System. This paper reports certain issues and difficulties that arose during a study to obtain this data.We also thank QinetiQ plc for funding through the IRAD programme

Temperature dependence on the mass susceptibility and mass magnetization of superparamagnetic Mn–Zn–ferrite nanoparticles as contrast agents for magnetic imaging of oil and gas reservoirs

The mass susceptibility (χmass) and mass magnetization (Mmass) were determined for a series of ternary manganese and zinc ferrite nanoparticles (Mn–Zn ferrite NPs, MnxZn1−xFe2O4) with different Mn:Zn ratios (0.08 ≤ x ≤ 4.67), prepared by the thermal decomposition reaction of the appropriate metal acetylacetonate complexes, and for the binary homologs (MxFe3−xO4, where M = Mn or Zn). Alteration of the Mn:Zn ratio in Mn–Zn ferrite NPs does not significantly affect the particle size. At room temperature and low applied field strength the mass susceptibility increases sharply as the Mn:Zn ratio increases, but above a ratio of 0.4 further increase in the amount of manganese results in the mass susceptibility decreasing slightly, reaching a plateau above Mn:Zn ≈ 2. The compositional dependence of the mass magnetization shows less of a variation at room temperature and high applied fields. The temperature dependence of the mass magnetization of Mn–Zn ferrite NPs is significantly less for Mn-rich compositions making them more suitable for downhole imaging at higher temperatures (>100 °C). For non-shale reservoirs, replacement of nMag by Mn-rich Mn–Zn ferrites will allow for significant signal-to-noise enhancement of 6.5× over NP magnetite

Structural and biochemical characterization of the exopolysaccharide deacetylase Agd3 required for Aspergillus fumigatus biofilm formation

The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Deletion of a gene encoding a putative deacetylase, Agd3, leads to defects in GAG deacetylation, biofilm formation, and virulence. Here, we show that Agd3 deacetylates GAG in a metal-dependent manner, and is the founding member of carbohydrate esterase family CE18. The active site is formed by four catalytic motifs that are essential for activity. The structure of Agd3 includes an elongated substrate-binding cleft formed by a carbohydrate binding module (CBM) that is the founding member of CBM family 87. Agd3 homologues are encoded in previously unidentified putative bacterial exopolysaccharide biosynthetic operons and in other fungal genomes. The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Here, the authors study an A. fumigatus enzyme that deacetylates GAG in a metal-dependent manner and constitutes a founding member of a new carbohydrate esterase family.Bio-organic Synthesi

Lunar exploration: opening a window into the history and evolution of the inner Solar System

The lunar geological record contains a rich archive of the history of the inner Solar System, including information relevant to understanding the origin and evolution of the Earth-Moon system, the geological evolution of rocky planets, and our local cosmic environment. This paper provides a brief review of lunar exploration to-date, and describes how future exploration initiatives will further advance our understanding of the origin and evolution of the Moon, the Earth-Moon system, and of the Solar System more generally. It is concluded that further advances will require the placing of new scientific instruments on, and the return of additional samples from, the lunar surface. Some of these scientific objectives can be achieved robotically, for example by in situ geochemical and geophysical measurements and through carefully targeted sample return missions. However, in the longer term, we argue that lunar science would greatly benefit from renewed human operations on the surface of the Moon, such as would be facilitated by implementing the recently proposed Global Exploration Roadmap

Postnatal quality of life in women after normal vaginal delivery and caesarean section

<p>Abstract</p> <p>Background</p> <p>Caesarean section might increase the incidence of surgical interventions and problems resulting from hospitalization and thus affecting quality of life in women after delivery. This study aimed to compare quality of life in women after normal delivery and caesarean section.</p> <p>Methods</p> <p>This was a prospective study. A sample of women with normal delivery and caesarean section from 5 health care centers in Isfahan, Iran were entered into the study. Quality of life was measured using the SF-36 at two points in time (time 1: 6 to 8 weeks after delivery; time 2: 12 to 14 weeks after delivery). Data were analyzed to compare quality of life in the two study groups.</p> <p>Results</p> <p>In all 100 women were interviewed (50 with normal delivery and 50 with caesarean section). Postnatal quality of life in both groups was improved from time1 to time 2. However, comparing the mean scores between the normal and caesarean delivery groups the results showed that in general the normal vaginal delivery group had a better quality of life for almost all subscales in both assessment times. The differences were significant for vitality (mean score 62.9 vs. 54.4 P = 0.03) and mental health (mean score 75.1 vs. 66.7, P = 0.03) at first assessment and for physical functioning (mean score 88.4 vs. 81.5, P = 0.03) at second evaluation. However, comparing the findings within each group the analysis showed that the normal vaginal delivery group improved more on physical health related quality of life while the caesarean section group improved more on mental health related quality of life.</p> <p>Conclusion</p> <p>Although the study did not show a clear cut benefit in favor of either methods of delivery that are normal vaginal delivery or caesarean section, the findings suggest that normal vaginal delivery might lead to a better quality of life especially resulting in a superior physical health. Indeed in the absence of medical indications normal vaginal delivery might be better to be considered as the first priority in term pregnancy.</p

Physiotherapy and occupational therapy vs no therapy in mild to moderate Parkinson disease: a randomized clinical trial

IMPORTANCE It is unclear whether physiotherapy and occupational therapy are clinically effective and cost-effective in Parkinson disease (PD). OBJECTIVE To perform a large pragmatic randomized clinical trial to evaluate the clinical effectiveness of individualized physiotherapy and occupational therapy in PD. DESIGN, SETTING, AND PARTICIPANTS The PD REHAB Trial was a multicenter, open-label, parallel group, controlled efficacy trial. A total of 762 patients with mild to moderate PD were recruited from 38 sites across the United Kingdom. Recruitment took place between October 2009 and June 2012, with 15 months of follow-up. INTERVENTIONS Participants with limitations in activities of daily living (ADL) were randomized to physiotherapy and occupational therapy or no therapy. MAIN OUTCOMES AND MEASURES The primary outcome was the Nottingham Extended Activities of Daily Living (NEADL) Scale score at 3 months after randomization. Secondary outcomes were health-related quality of life (assessed by Parkinson Disease Questionnaire–39 and EuroQol-5D); adverse events; and caregiver quality of life. Outcomes were assessed before trial entry and then 3, 9, and 15 months after randomization. RESULTS Of the 762 patients included in the study (mean [SD] age, 70 [9.1] years), 381 received physiotherapy and occupational therapy and 381 received no therapy. At 3 months, there was no difference between groups in NEADL total score (difference, 0.5 points; 95%CI, −0.7 to 1.7; P = .41) or Parkinson Disease Questionnaire–39 summary index (0.007 points; 95%CI, −1.5 to 1.5; P = .99). The EuroQol-5D quotient was of borderline significance in favor of therapy (−0.03; 95%CI, −0.07 to −0.002; P = .04). The median therapist contact time was 4 visits of 58 minutes over 8 weeks. Repeated-measures analysis showed no difference in NEADL total score, but Parkinson Disease Questionnaire–39 summary index (diverging 1.6 points per annum; 95%CI, 0.47 to 2.62; P = .005) and EuroQol-5D score (0.02; 95%CI, 0.00007 to 0.03; P = .04) showed small differences in favor of therapy. There was no difference in adverse events. CONCLUSIONS AND RELEVANCE Physiotherapy and occupational therapy were not associated with immediate or medium-term clinically meaningful improvements in ADL or quality of life in mild to moderate PD. This evidence does not support the use of low-dose, patient-centered, goal-directed physiotherapy and occupational therapy in patients in the early stages of PD. Future research should explore the development and testing of more structured and intensive physical and occupational therapy programs in patients with all stages of PD

One-stop diagnostic breast clinics: how often are breast cancers missed?

The aim of this study was to estimate the number of patients discharged from a symptomatic breast clinic who subsequently develop breast cancer and to determine how many of these cancers had been ‘missed' at initial assessment. Over a 3-year period, 7004 patients were discharged with a nonmalignant diagnosis. Twenty-nine patients were subsequently diagnosed with breast cancer over the next 36 months. This equates to a symptomatic ‘interval' cancer rate of 4.1 per 1000 women in the 36 months after initial assessment (0.9 per 1000 women within 12 months, 2.6 per 1000 women within 24 months). The lowest sensitivity of initial assessment was seen in patients of 40–49 years of age, and these patients present the greatest imaging and diagnostic challenge. Following multidisciplinary review, a consensus was reached on whether a cancer had been missed or not. No delay occurred in 10 patients (35%) and probably no delay in 7 patients (24%). Possible delay occurred in three patients (10%) and definite delay in diagnosis (i.e., a ‘missed' cancer) occurred in only nine patients (31%). The overall diagnostic accuracy of ‘triple' assessment is 99.6% and the ‘missed' cancer rate is 1.7 per 1000 women discharged

Why it takes an 'ontological shock' to prompt increases in small firm resilience : sensemaking, emotions and flood risk

This article uses a sensemaking approach to understand small firms’ responses to the threat of external shocks. By analysing semi-structured interviews with owners of flooded small firms, we investigate how owners process flood experiences and explore why such experiences do not consistently lead to the resilient adaptation of premises. We, conclude that some of the explanation for low levels of adaptation relates to a desire to defend existing sensemaking structures and associated identities. Sensemaking structures are only revised if these structures are not critical to business identity, or if a flood constitutes an ‘ontological shock’ and renders untenable existing assumptions regarding long-term business continuity. This article has implications for adaptation to the growing risk of flooding, climate change and external shocks. Future research analysing external shocks would benefit from using a sensemaking approach and survey studies should include measurements of ‘ontological’ impact as well as material and financial damage. In addition, those designing information campaigns should take account of small firms’ resistance to information that threatens their existing sensemaking structures and social identities