The Surgical Release of Dupuytren's Contracture Using Multiple Transverse Incisions.

Dupuytren's contracture is a condition commonly encountered by hand surgeons, although it is rare in the Asian population. Various surgical procedures for Dupuytren's contracture have been reported, and the outcomes vary according to the treatment modalities. We report the treatment results of segmental fasciectomies with multiple transverse incisions for patients with Dupuytren's contracture. The cases of seven patients who underwent multiple segmental fasciectomies with multiple transverse incisions for Dupuytren's contracture from 2006 to 2011 were reviewed retrospectively. Multiple transverse incisions to the severe contracture sites were performed initially, and additional incisions to the metacarpophalangeal (MCP) joints, and the proximal interphalangeal (PIP) joints were performed if necessary. Segmental fasciectomies by removing the fibromatous nodules or cords between the incision lines were performed and the wound margins were approximated. The mean range of motion of the involved MCP joints and PIP joints was fully recovered. During the follow-up periods, there was no evidence of recurrence or progression of disease. Multiple transverse incisions for Dupuytren's contracture are technically challenging, and require a high skill level of hand surgeons. However, we achieved excellent correction of contractures with no associated complications. Therefore, segmental fasciectomies with multiple transverse incisions can be a good treatment option for Dupuytren's contracture

Modulation transfer function obtained from image structures

A new and relatively simple method for edge gradient analysis (EGA) has been developed to determine the modulation transfer function (MTF) of photogrammetrical systems. The MTF can be calculated as the ratio of the amplitude of those frequencies present in the original edge to the amplitude of the same frequency in the scanned edge image. Thus a differentiation of the edge scan - as usually implemented - is not necessary. In order to avoid a division by zero we multiplied the edge images by the so called Hanning function before performing the Fourier analysis. From the point of noise sensitivity the method using a Hanning window is advantageous in comparison to the edge differentiation method. The edge gradient analysis method and the grating pattern method are compared. Artificial edge, natural roof edge, and grating patterns were used to determine the quality of the photogrammetrical system. Good agreement of all MTF measurements was found. Furthermore, the resolution found from MTF curves agreed well with the resolution obtained from threebar targets. Generally, the MTF curves obtained from patterns in the flight direction were lower than the MTF's perpendicular to the flight direction due to airplane movement. The influence of linear image motion and its compensation was examined and is discussed. Furthermore, the longitudinal motion of the object as defect of focus is studied analytically and experimentally for a close range

Evaluation of the ECOSSE model for simulating soil organic carbon under Miscanthus and short rotation coppice-willow crops in Britain

In this paper, we focus on the impact on soil organic carbon (SOC) of two dedicated energy crops: perennial grass Miscanthus x Giganteus (Miscanthus) and short rotation coppice (SRC)-willow. The amount of SOC sequestered in the soil is a function of site-specific factors including soil texture, management practices, initial SOC levels and climate; for these reasons, both losses and gains in SOC were observed in previous Miscanthus and SRC-willow studies. The ECOSSE model was developed to simulate soil C dynamics and greenhouse gas emissions in mineral and organic soils. The performance of ECOSSE has already been tested at site level to simulate the impacts of land-use change to short rotation forestry (SRF) on SOC. However, it has not been extensively evaluated under other bioenergy plantations, such as Miscanthus and SRC-willow. Twenty-nine locations in the United Kingdom, comprising 19 paired transitions to SRC-willow and 20 paired transitions to Miscanthus, were selected to evaluate the performance of ECOSSE in predicting SOC and SOC change from conventional systems (arable and grassland) to these selected bioenergy crops. The results of the present work revealed a strong correlation between modelled and measured SOC and SOC change after transition to Miscanthus and SRC-willow plantations, at two soil depths (0–30 and 0–100 cm), as well as the absence of significant bias in the model. Moreover, model error was within (i.e. not significantly larger than) the measurement error. The high degrees of association and coincidence with measured SOC under Miscanthus and SRC-willow plantations in the United Kingdom, provide confidence in using this process-based model for quantitatively predicting the impacts of future land use on SOC, at site level as well as at national level

Evaluation of the ECOSSE model for simulating soilcarbon under short rotation forestry energy crops in Britain

Understanding and predicting the effects of land-use change to short rotation forestry (SRF) on soil carbon (C) is an important requirement for fully assessing the C mitigation potential of SRF as a bioenergy crop. There is little current knowledge of SRF in the UK and in particular a lack of consistent measured data sets on the direct impacts of land use change on soil C stocks. The ECOSSE model was developed to simulate soil C dynamics and greenhouse gas (GHG) emissions in mineral and organic soils. The ECOSSE model has already been applied spatially to simulate land-use change impacts on soil C and GHG emissions. However, it has not been extensively evaluated under SRF. Eleven sites comprising 29 transitions in Britain, representing land-use change from nonwoodland land uses to SRF, were selected to evaluate the performance of ECOSSE in predicting soil C and soil C change in SRF plantations. The modelled C under SRF showed a strong correlation with the soil C measurements at both 0–30 cm (R = 0.93) and 0–100 cm soil depth (R = 0.82). As for the SRF plots, the soil C at the reference sites have been accurately simulated by the model. The extremely high correlation for the reference fields (R ≥ 0.99) shows a good performance of the model spin-up. The statistical analysis of the model performance to simulate soil C and soil C changes after land-use change to SRF highlighted the absence of significant error between modelled and measured values as well as the absence of significant bias in the model. Overall, this evaluation reinforces previous studies on the ability of ECOSSE to simulate soil C and emphasize its accuracy to simulate soil C under SRF plantations

3D Growth of Cancer Cells Elicits Sensitivity to Kinase Inhibitors but Not Lipid Metabolism Modifiers

Tumor cells exhibit altered lipid metabolism compared with normal cells. Cell signaling kinases are important for regulating lipid synthesis and energy storage. How upstream kinases regulate lipid content, versus direct targeting of lipid-metabolizing enzymes, is currently unexplored. We evaluated intracellular lipid concentrations in prostate and breast tumor spheroids, treated with drugs directly inhibiting metabolic enzymes fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC), diacylglyceride acyltransferase (DGAT), and pyruvate dehydrogenase kinase (PDHK), or cell signaling kinase enzymes PI3K, AKT, and mTOR with lipidomic analysis. We assessed whether baseline lipid profiles corresponded to inhibitors' effectiveness in modulating lipid profiles in three-dimensional (3D) growth and their relationship to therapeutic activity. Inhibitors against PI3K, AKT, and mTOR significantly inhibited MDA-MB-468 and PC3 cell growth in two-dimensional (2D) and 3D spheroid growth, while moderately altering lipid content. Conversely, metabolism inhibitors against FASN and DGAT altered lipid content most effectively, while only moderately inhibiting growth compared with kinase inhibitors. The FASN and ACC inhibitors' effectiveness in MDA-MB-468, versus PC3, suggested the former depended more on synthesis, whereas the latter may salvage lipids. Although baseline lipid profiles did not predict growth effects, lipid changes on therapy matched the growth effects of FASN and DGAT inhibitors. Several phospholipids, including phosphatidylcholine, were also upregulated following treatment, possibly via the Kennedy pathway. As this promotes tumor growth, combination studies should include drugs targeting it. Two-dimensional drug screening may miss important metabolism inhibitors or underestimate their potency. Clinical studies should consider serial measurements of tumor lipids to prove target modulation. Pretherapy tumor classification by de novo lipid synthesis versus uptake may help demonstrate efficacy

Rifampicin and clarithromycin (extended release) versus rifampicin and streptomycin for limited Buruli ulcer lesions: a randomised, open-label, non-inferiority phase 3 trial.

BACKGROUND: Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans infection that damages the skin and subcutis. It is most prevalent in western and central Africa and Australia. Standard antimicrobial treatment with oral rifampicin 10 mg/kg plus intramuscular streptomycin 15 mg/kg once daily for 8 weeks (RS8) is highly effective, but streptomycin injections are painful and potentially harmful. We aimed to compare the efficacy and tolerability of fully oral rifampicin 10 mg/kg plus clarithromycin 15 mg/kg extended release once daily for 8 weeks (RC8) with that of RS8 for treatment of early Buruli ulcer lesions. METHODS: We did an open-label, non-inferiority, randomised (1:1 with blocks of six), multicentre, phase 3 clinical trial comparing fully oral RC8 with RS8 in patients with early, limited Buruli ulcer lesions. There were four trial sites in hospitals in Ghana (Agogo, Tepa, Nkawie, Dunkwa) and one in Benin (Pobè). Participants were included if they were aged 5 years or older and had typical Buruli ulcer with no more than one lesion (caterories I and II) no larger than 10 cm in diameter. The trial was open label, and neither the investigators who took measurements of the lesions nor the attending doctors were masked to treatment assignment. The primary clinical endpoint was lesion healing (ie, full epithelialisation or stable scar) without recurrence at 52 weeks after start of antimicrobial therapy. The primary endpoint and safety were assessed in the intention-to-treat population. A sample size of 332 participants was calculated to detect inferiority of RC8 by a margin of 12%. This study was registered with ClinicalTrials.gov, NCT01659437. FINDINGS: Between Jan 1, 2013, and Dec 31, 2017, participants were recruited to the trial. We stopped recruitment after 310 participants. Median age of participants was 14 years (IQR 10-29) and 153 (52%) were female. 297 patients had PCR-confirmed Buruli ulcer; 151 (51%) were assigned to RS8 treatment, and 146 (49%) received oral RC8 treatment. In the RS8 group, lesions healed in 144 (95%, 95% CI 91 to 98) of 151 patients, whereas lesions healed in 140 (96%, 91 to 99) of 146 patients in the RC8 group. The difference in proportion, -0·5% (-5·2 to 4·2), was not significantly greater than zero (p=0·59), showing that RC8 treatment is non-inferior to RS8 treatment for lesion healing at 52 weeks. Treatment-related adverse events were recorded in 20 (13%) patients receiving RS8 and in nine (7%) patients receiving RC8. Most adverse events were grade 1-2, but one (1%) patient receiving RS8 developed serious ototoxicity and ended treatment after 6 weeks. No patients needed surgical resection. Four patients (two in each study group) had skin grafts. INTERPRETATION: Fully oral RC8 regimen was non-inferior to RS8 for treatment of early, limited Buruli ulcer and was associated with fewer adverse events. Therefore, we propose that fully oral RC8 should be the preferred therapy for early, limited lesions of Buruli ulcer. FUNDING: WHO with additional support from MAP International, American Leprosy Missions, Fondation Raoul Follereau France, Buruli ulcer Groningen Foundation, Sanofi-Pasteur, and BuruliVac

Novel study design to assess the utility of the copd assessment test in a primary care setting

The quality of a consultation provided by a physician can have a profound impact on the quality of care and patient engagement in treatment decisions. When the COPD Assessment Test (CAT) was developed, one of its aims was to aid the communication between physician and patient about the impact of COPD. We developed a novel study design to assess this in a primary care consultation. Primary care physicians across five countries in Europe conducted videoed consultations with six standardised COPD patients (played by trained actors) which had patient-specific issues that the physician needed to identify through questioning. Half the physicians saw the patients with the completed CAT, and half without. Independent assessors scored the physicians on their ability to identify and address the patient-specific issues, review standard COPD aspects, their understanding of the case and their overall performance. This novel study design presented many challenges which needed to be addressed to achieve an acceptable level of robustness to assess the utility of the CAT. This paper discusses these challenges and the measures adopted to eliminate or minimise their impact on the study results

High resolution spatial modelling of greenhouse gas emissions from land use change to energy crops in the UK

We implemented a spatial application of a previously evaluated model of soil GHG emissions, ECOSSE, in the United Kingdom to examine the impacts to 2050 of land-use transitions from existing land use, rotational cropland, permanent grassland or woodland, to six bioenergy crops; three ‘first-generation’ energy crops: oilseed rape, wheat and sugar beet, and three ‘second-generation’ energy crops: Miscanthus, short rotation coppice willow (SRC) and short rotation forestry poplar (SRF). Conversion of rotational crops to Miscanthus, SRC and SRF and conversion of permanent grass to SRF show beneficial changes in soil GHG balance over a significant area. Conversion of permanent grass to Miscanthus, permanent grass to SRF and forest to SRF shows detrimental changes in soil GHG balance over a significant area. Conversion of permanent grass to wheat, oilseed rape, sugar beet and SRC and all conversions from forest show large detrimental changes in soil GHG balance over most of the United Kingdom, largely due to moving from uncultivated soil to regular cultivation. Differences in net GHG emissions between climate scenarios to 2050 were not significant. Overall, SRF offers the greatest beneficial impact on soil GHG balance. These results provide one criterion for selection of bioenergy crops and do not consider GHG emission increases/decreases resulting from displaced food production, bio-physical factors (e.g. the energy density of the crop) and socio-economic factors (e.g. expenditure on harvesting equipment). Given that the soil GHG balance is dominated by change in soil organic carbon (SOC) with the difference among Miscanthus, SRC and SRF largely determined by yield, a target for management of perennial energy crops is to achieve the best possible yield using the most appropriate energy crop and cultivar for the local situation

The stealth episome: suppression of gene expression on the excised genomic island PPHGI-1 from Pseudomonas syringae pv. phaseolicola

Pseudomonas syringae pv. phaseolicola is the causative agent of halo blight in the common bean, Phaseolus vulgaris. P. syringae pv. phaseolicola race 4 strain 1302A contains the avirulence gene avrPphB (syn. hopAR1), which resides on PPHGI-1, a 106 kb genomic island. Loss of PPHGI-1 from P. syringae pv. phaseolicola 1302A following exposure to the hypersensitive resistance response (HR) leads to the evolution of strains with altered virulence. Here we have used fluorescent protein reporter systems to gain insight into the mobility of PPHGI-1. Confocal imaging of dual-labelled P. syringae pv. phaseolicola 1302A strain, F532 (dsRFP in chromosome and eGFP in PPHGI-1), revealed loss of PPHGI-1::eGFP encoded fluorescence during plant infection and when grown in vitro on extracted leaf apoplastic fluids. Fluorescence-activated cell sorting (FACS) of fluorescent and non-fluorescent PPHGI-1::eGFP F532 populations showed that cells lost fluorescence not only when the GI was deleted, but also when it had excised and was present as a circular episome. In addition to reduced expression of eGFP, quantitative PCR on sub-populations separated by FACS showed that transcription of other genes on PPHGI-1 (avrPphB and xerC) was also greatly reduced in F532 cells harbouring the excised PPHGI-1::eGFP episome. Our results show how virulence determinants located on mobile pathogenicity islands may be hidden from detection by host surveillance systems through the suppression of gene expression in the episomal state