Objective and methodsDysferlin encoded by DYSF deficiency leads to two main phenotypes, limb girdle muscular dystrophy (LGMD) 2B and Miyoshi myopathy. To reveal in detail the mutational and clinical features of LGMD2B in Japan, we observed 40 Japanese patients in 36 families with LGMD2B in whom dysferlin mutations were confirmed.Results and conclusionsThree mutations (c.1566C>G, c.2997G>T and c.4497delT) were relatively more prevalent. The c.2997G>T mutation was associated with late onset, proximal dominant forms of dysferlinopathy, a high probability that muscle weakness started in an upper limb and lower serum creatine kinase (CK) levels. The clinical features of LGMD2B are as follows: (1) onset in the late teens or early adulthood, except patients homozygous for the c.2997G>T mutation; (2) lower limb weakness at onset; (3) distal change of lower limbs on muscle CT at an early stage; (4) impairment of lumbar erector spinal muscles on muscle CT at an early stage; (5) predominant involvement of proximal upper limbs; (6) preservation of function of the hands at late stage; (7) preservation of strength in neck muscles at late stage; (8) lack of facial weakness or dysphagia; (9) avoidance of scoliosis; (10) hyper-Ckaemia; (11) preservation of cardiac function; and (12) a tendency for respiratory function to decline with disease duration. It is important that the late onset phenotype is found with prevalent mutations.

The Japanese surveillance committee conducted the first nationwide surveillance of antimicrobial susceptibility patterns of uropathogens responsible for female acute uncomplicated cystitis at 43 hospitals throughout Japan from April 2009 to November 2010. In this study, the causative bacteria (Escherichia coli and Staphylococcus saprophyticus) and their susceptibility to various antimicrobial agents were investigated by isolation and culturing of bacteria from urine samples. In total, 387 strains were isolated from 461 patients, including E. coli (n = 301, 77.8 %), S. saprophyticus (n = 20, 5.2 %), Klebsiella pneumoniae (n = 13, 3.4 %), and Enterococcus faecalis (n = 11, 2.8 %). S. saprophyticus was significantly more common in premenopausal women (P = 0.00095). The minimum inhibitory concentrations of 19 antibacterial agents used for these strains were determined according to the Clinical and Laboratory Standards Institute manual. At least 87 % of E. coli isolates showed susceptibility to fluoroquinolones and cephalosporins, and 100 % of S. saprophyticus isolates showed susceptibility to fluoroquinolones and aminoglycosides. The proportions of fluoroquinolone-resistant E. coli strains and extended-spectrum β-lactamase (ESBL)-producing E. coli strains were 13.3 % and 4.7 %, respectively. It is important to confirm the susceptibility of causative bacteria for optimal antimicrobial therapy, and empiric antimicrobial agents should be selected by considering patient characteristics and other factors. However, the number of isolates of fluoroquinolone-resistant or ESBL-producing strains in gram-negative bacilli may be increasing in patients with urinary tract infections (UTIs) in Japan. Therefore, these data present important information for the proper treatment of UTIs and will serve as a useful reference for future surveillance studies.

<p><strong>Abstract.</strong> Changes in aerosols cause a change in net top-of-the-atmosphere (ToA) short-wave and long-wave radiative fluxes, rapid adjustments in clouds, water vapour and temperature, and cause an effective radiative forcing (ERF) of the planetary energy budget. The diverse sources of model uncertainty and the computational cost of running climate models make it difficult to isolate the main causes of aerosol ERF uncertainty and to understand how observations can be used to constrain it. We explore the aerosol ERF uncertainty by using fast model emulators to generate a very large set of aerosol-climate model variants that span the model uncertainty due to twenty-seven parameters related to atmospheric and aerosol processes. Sensitivity analyses shows that the uncertainty in the ToA flux is dominated (around 80 %) by uncertainties in the physical atmosphere model, particularly parameters that affect cloud reflectivity. However, uncertainty in the change in ToA flux caused by aerosol emissions over the industrial period (the aerosol ERF) is controlled by a combination of uncertainties in aerosol (around 60 %) and physical atmosphere (around 40 %) parameters. Four of the atmospheric and aerosol parameters that cause uncertainty in short-wave ToA flux (mostly parameters that directly scale cloud reflectivity, cloud water content or cloud droplet concentrations) also account for around 60% of the aerosol ERF uncertainty. The common causes of uncertainty mean that constraining the modelled planetary brightness to tightly match satellite observations changes the lower 95 % credible aerosol ERF value from −2.65 Wm<sup>−2</sup> to −2.37 Wm<sup>−2</sup>. This suggests the strongest forcings (below around −2.4 Wm<sup>−2</sup>) are inconsistent with observations. These results show that, regardless of the fact that the ToA flux is an order of magnitude larger than the aerosol ERF, the observed flux can constrain the uncertainty in ERF because their values are connected by constrainable process parameters. The key to reducing the aerosol ERF uncertainty further will be to identify observations that can additionally constrain individual parameter ranges and/or combined parameter effects, which can be achieved through sensitivity analysis of perturbed parameter ensembles.</p>

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We examined the immunopathology and the expression of human immunodeficiency virus type 1 (HIV-1) in lumbosacral dorsal root ganglia (DRGs) from 16 patients with acquired immunodeficiency syndrome (AIDS) and 10 HIV-1-seronegative controls. Using in situ hybridization, we detected HIV-1 RNA in a few perivascular cells in DRGs from five of 16 AIDS patients (31%). In addition, using polymerase chain reaction, we detected HIV-1 DNA more frequently in DRGs from four of five AIDS patients (80%) examined. We detected interleukin-6 (IL-6) immunoreactivity in endothelial cells in DRGs from seven of 16 AIDS patients (44%) but from none of 10 HIV-1-seronegative controls (0%). We found more nodules of Nageotte, CD8+ T lymphocytes, and intercellular adhesion molecule-1 (ICAM-1)-positive endothelial cells and mononuclear cells in DRGs from AIDS patients than in DRGs from controls. Increased numbers of nodules of Nageotte in DRGs of AIDS patients were associated with detection of HIV-1 RNA by in situ hybridization and detection of IL-6 by immunohistochemistry. We conclude that low levels of replication of HIV-1, through cytotoxic T lymphocytes or expression of cytokines, may play a role in the subclinical degeneration of sensory neurons frequently observed in DRGs of AIDS patients.