Cmr is a redox-responsive regulator of DosR that contributes to M. tuberculosis virulence.

Mycobacterium tuberculosis (MTb) is the causative agent of pulmonary tuberculosis (TB). MTb colonizes the human lung, often entering a non-replicating state before progressing to life-threatening active infections. Transcriptional reprogramming is essential for TB pathogenesis. In vitro, Cmr (a member of the CRP/FNR super-family of transcription regulators) bound at a single DNA site to act as a dual regulator of cmr transcription and an activator of the divergent rv1676 gene. Transcriptional profiling and DNA-binding assays suggested that Cmr directly represses dosR expression. The DosR regulon is thought to be involved in establishing latent tuberculosis infections in response to hypoxia and nitric oxide. Accordingly, DNA-binding by Cmr was severely impaired by nitrosation. A cmr mutant was better able to survive a nitrosative stress challenge but was attenuated in a mouse aerosol infection model. The complemented mutant exhibited a ∼2-fold increase in cmr expression, which led to increased sensitivity to nitrosative stress. This, and the inability to restore wild-type behaviour in the infection model, suggests that precise regulation of the cmr locus, which is associated with Region of Difference 150 in hypervirulent Beijing strains of Mtb, is important for TB pathogenesis.

Structure and Function of the PiuA and PirA Siderophore-Drug Receptors from Pseudomonas aeruginosa and Acinetobacter baumannii.

The outer membrane of Gram-negative bacteria presents an efficient barrier to the permeation of antimicrobial molecules. One strategy pursued to circumvent this obstacle is to hijack transport systems for essential nutrients, such as iron. BAL30072 and MC-1 are two monobactams conjugated to a dihydroxypyridone siderophore that are active against Pseudomonas aeruginosa and Acinetobacter baumannii Here, we investigated the mechanism of action of these molecules in A. baumannii We identified two novel TonB-dependent receptors, termed Ab-PiuA and Ab-PirA, that are required for the antimicrobial activity of both agents. Deletion of either piuA or pirA in A. baumannii resulted in 4- to 8-fold-decreased susceptibility, while their overexpression in the heterologous host P. aeruginosa increased susceptibility to the two siderophore-drug conjugates by 4- to 32-fold. The crystal structures of PiuA and PirA from A. baumannii and their orthologues from P. aeruginosa were determined. The structures revealed similar architectures; however, structural differences between PirA and PiuA point to potential differences between their cognate siderophore ligands. Spontaneous mutants, selected upon exposure to BAL30072, harbored frameshift mutations in either the ExbD3 or the TonB3 protein of A. baumannii, forming the cytoplasmic-membrane complex providing the energy for the siderophore translocation process. The results of this study provide insight for the rational design of novel siderophore-drug conjugates against problematic Gram-negative pathogens.

The relationship between therapist-rated function and patient-reported outcome measures.

STUDY DESIGN: Prospective cohort study. INTRODUCTION: Some third-party payers require hand therapists to rate patient's functional disability based on patient self-rating using patient-reported outcome measures (PROMs), objective measurements of impairment, and observation of functional tasks-hand therapist-rated function (HTRF). PURPOSE OF THE STUDY: To test the correlation between HTRF and PROMs (upper limb functional index [ULFI] and Patient-Reported Outcomes Measurement Information System upper extremity [PROMIS UE]) and its association with psychological factors. METHODS: In 2014, 100 new patients with upper extremity illness presenting to hand therapists were asked to participate in an observational cross-sectional study. Demographic-, condition-related, and psychological factors were obtained in addition to PROMs and HTRF. RESULTS: HTRF correlated moderately with PROMIS UE (r = -0.49, P < .001) and ULFI (r = -0.56, P < .001). Correlation between PROMIS UE and ULFI was strong (r = 0.78, P < .001). Psychological factors explained most of the variations in both HTRF and PROMs. CONCLUSIONS: Hand therapists' ratings of patient function correlate less strongly with PROMs than PROMs correlate with one other. The discrepancy between HTRF and PROMs may offer an opportunity to address stress, distress, or ineffective coping strategies that can interfere with recovery-an opportunity for therapists and patients to collaborate and develop goals and for future research to develop effective and feasible strategies for hand therapists. LEVEL OF EVIDENCE: Level II, diagnostic study.

Swarming motility is modulated by expression of the putative xenosiderophore transporter SppR-SppABCD in Pseudomonas aeruginosa PA14.

In the present study, we characterised the putative peptide ABC transporter SppABCD, which is co-transcribed with the TonB-dependent receptor SppR in Pseudomonas aeruginosa PA14. However, our data show that this transporter complex is not involved in the uptake of peptides. The fact that the TonB-dependent receptor SppR is regulated by an iron starvation ECF sigma factor suggested that this transporter is probably involved in the uptake of xenosiderophores. Therefore, we screened culture supernatants of 23 siderophore-producing bacteria for their ability to induce the expression of the SppR-regulating ECF sigma factor. However, none of them had an effect on the expression of this ECF sigma factor. Since the spp operon is not expressed under standard laboratory conditions, we overexpressed it from plasmids in PA14, which led to an impairment of its swarming motility on semisolid agar. Since we excluded the possibility that the uptake of a culture medium component was responsible for the observed phenotype, we hypothesize that the Spp transport system is involved in the uptake of a compound from the periplasmic space or a compound secreted by P. aeruginosa. Furthermore, we found that rhamnolipid synthesis was decreased while biofilm and exopolysaccharide synthesis was slightly increased upon overexpression of the spp operon. Moreover, we observed an impact of spp overexpression on regulation of genes involved in siderophore and phenazine biosynthesis.

Factors Associated With Reoperation After Fixation of Displaced Olecranon Fractures.

BACKGROUND: Surgery for fixation of olecranon fractures is associated with reoperation, mostly for implant removal. A study of a large cohort of patients treated by many different surgeons allows us to determine if specific techniques or implants are associated with a higher rate of reoperation. QUESTIONS/PURPOSES: After open reduction and internal fixation of isolated olecranon fractures, what factors are associated with (1) reoperation and (2) implant removal? METHODS: Three hundred ninety-two adult patients who had operative treatment of a displaced olecranon fracture not associated with other fractures, dislocation, or subluxation at two area hospitals between January 2002 and May 2014 were analyzed to determine factors associated with reoperation. One hundred thirty-eight (35%) patients had plate and screw fixation and 254 (65%) tension band wiring. Nearly 100% of patients with displaced olecranon fractures are currently treated operatively at our hospitals. All patients were followed for at least four months. Two hundred three of the 392 (52%) patients were followed for one year or more. Ninety-nine patients (25%) had a second operation, 92 (93%) at least in part for implant removal (12 for wire migration [3% of all fractures, 12% of reoperations]). We considered patient-related, fracture-related, and implant-related endpoints as possible factors associated with reoperation. With a total sample size of 99 reoperations, an α of 0.05, and an effect size of 0.3, we had 87% power. RESULTS: Reoperation was less common in men (36 [36%], women: 63 [64%]; adjusted odds ratio, 0.32; 95% confidence interval, 0.18-0.56; p < 0.001) and older patients (adjusted odds ratio, 0.75; 95% confidence interval, 0.65-0.87; p < 0.001). Similarly, request for implant removal was less in men (33 [36%], women: 59 [64%], adjusted odds ratio, 0.31; 95% confidence interval, 0.18-0.56; p < 0.001) and older patients (adjusted odds ratio, 0.75; 95% confidence interval, 0.65-0.87; p < 0.001). CONCLUSIONS: Patients who have operative fixation of a fracture of the olecranon can be counseled that most patients keep their implants, that only 3% experience implant migration, and that technical factors such as the type or configuration of an implant seem less important than personal factors in determining who requests a second surgery for implant removal. LEVEL OF EVIDENCE: Level III, prognostic study.

What Factors are Associated With a Surgical Site Infection After Operative Treatment of an Elbow Fracture?

BACKGROUND: Surgical site infections are one of the more common major complications of elbow fracture surgery and can contribute to other adverse outcomes, prolonged hospital stays, and increased healthcare costs. QUESTIONS/PURPOSES: We asked: (1) What are the factors associated with a surgical site infection after elbow fracture surgery? (2) When taking the subset of closed elbow fractures only, what are the factors associated with a surgical site infection? (3) What are the common organisms isolated from an elbow infection after open treatment? METHODS: One thousand three hundred twenty adult patients underwent surgery for an elbow fracture between January 2002 and July 2014 and were included in our study. Forty-eight of 1320 patients (4%) had a surgical site infection develop. Thirty-four of 1113 patients with a closed fracture (3%) had a surgical site infection develop. RESULTS: For all elbow fractures, use of plate and screw fixation (adjusted odds ratio [OR]= 2.2; 95% CI, 1.0-4.5; p = 0.041) and use of external fixation before surgery (adjusted OR = 4.7; 95% CI, 1.1-21; p = 0.035) were associated with higher infection rates. When subset analysis was performed for closed fractures, only smoking (adjusted OR = 2.2; 95% CI, 1.1-4.5; p = 0.023) was associated with higher infection rates. Staphylococcus aureus was the most common bacteria cultured (59%). CONCLUSIONS: The only modifiable risk factor for a surgical site infection after open reduction and internal fixation was cigarette smoking. Plate fixation and temporary external fixation are likely surrogates for more complex injuries, therefore no recommendations should be inferred from this association. Surgeons should counsel patients who smoke. LEVEL OF EVIDENCE: Level IV, prognostic study.

The Pseudomonas aeruginosa PA14 ABC Transporter NppA1A2BCD Is Required for Uptake of Peptidyl Nucleoside Antibiotics.

UNLABELLED: Analysis of the genome sequence of Pseudomonas aeruginosa PA14 revealed the presence of an operon encoding an ABC-type transporter (NppA1A2BCD) showing homology to the Yej transporter of Escherichia coli. The Yej transporter is involved in the uptake of the peptide-nucleotide antibiotic microcin C, a translation inhibitor that targets the enzyme aspartyl-tRNA synthetase. Furthermore, it was recently shown that the Opp transporter from P. aeruginosa PAO1, which is identical to Npp, is required for uptake of the uridyl peptide antibiotic pacidamycin, which targets the enzyme translocase I (MraY), which is involved in peptidoglycan synthesis. We used several approaches to further explore the substrate specificity of the Npp transporter. Assays of growth in defined minimal medium containing peptides of various lengths and amino acid compositions as sole nitrogen sources, as well as Biolog Phenotype MicroArrays, showed that the Npp transporter is not required for di-, tri-, and oligopeptide uptake. Overexpression of the npp operon increased susceptibility not just to pacidamycin but also to nickel chloride and the peptidyl nucleoside antibiotic blasticidin S. Furthermore, heterologous expression of the npp operon in a yej-deficient mutant of E. coli resulted in increased susceptibility to albomycin, a naturally occurring sideromycin with a peptidyl nucleoside antibiotic. Additionally, heterologous expression showed that microcin C is recognized by the P. aeruginosa Npp system. Overall, these results suggest that the NppA1A2BCD transporter is involved in the uptake of peptidyl nucleoside antibiotics by P. aeruginosa PA14. IMPORTANCE: One of the world's most serious health problems is the rise of antibiotic-resistant bacteria. There is a desperate need to find novel antibiotic therapeutics that either act on new biological targets or are able to bypass known resistance mechanisms. Bacterial ABC transporters play an important role in nutrient uptake from the environment. These uptake systems could also be exploited by a Trojan horse strategy to facilitate the transport of antibiotics into bacterial cells. Several natural antibiotics mimic substrates of peptide uptake routes. In this study, we analyzed an ABC transporter involved in the uptake of nucleoside peptidyl antibiotics. Our data might help to design drug conjugates that may hijack this uptake system to gain access to cells.

Quantification of Fluoroquinolone Uptake through the Outer Membrane Channel OmpF of Escherichia coli.

Decreased drug accumulation is a common cause of antibiotic resistance in microorganisms. However, there are few reliable general techniques capable of quantifying drug uptake through bacterial membranes. We present a semiquantitative optofluidic assay for studying the uptake of autofluorescent drug molecules in single liposomes. We studied the effect of the Escherichia coli outer membrane channel OmpF on the accumulation of the fluoroquinolone antibiotic, norfloxacin, in proteoliposomes. Measurements were performed at pH 5 and pH 7, corresponding to two different charge states of norfloxacin that bacteria are likely to encounter in the human gastrointestinal tract. At both pH values, the porins significantly enhance drug permeation across the proteoliposome membranes. At pH 5, where norfloxacin permeability across pure phospholipid membranes is low, the porins increase drug permeability by 50-fold on average. We estimate a flux of about 10 norfloxacin molecules per second per OmpF trimer in the presence of a 1 mM concentration gradient of norfloxacin. We also performed single channel electrophysiology measurements and found that the application of transmembrane voltages causes an electric field driven uptake in addition to concentration driven diffusion. We use our results to propose a physical mechanism for the pH mediated change in bacterial susceptibility to fluoroquinolone antibiotics.

Incidence of surgical site infection after spine surgery: what is the impact of the definition of infection?

BACKGROUND: Orthopaedic surgical site infections (SSIs) can delay recovery, add impairments, and decrease quality of life, particularly in patients undergoing spine surgery, in whom SSIs may also be more common. Efforts to prevent and treat SSIs of the spine rely on the identification and registration of these adverse events in large databases. The effective use of these databases to answer clinical questions depends on how the conditions in question, such as infection, are defined in the databases queried, but the degree to which different definitions of infection might cause different risk factors to be identified by those databases has not been evaluated. QUESTIONS/PURPOSES: The purpose of this study was to determine whether different definitions of SSI identify different risk factors for SSI. Specifically, we compared the International Classification of Diseases, 9th Revision (ICD-9) coding, Centers for Disease Control and Prevention (CDC) criteria for deep infection, and incision and débridement for infection to determine if each is associated with distinct risk factors for SSI. METHODS: In this single-center retrospective study, a sample of 5761 adult patients who had an orthopaedic spine surgery between January 2003 and August 2013 were identified from our institutional database. The mean age of the patients was 56 years (± 16 SD), and slightly more than half were men. We applied three different definitions of infection: ICD-9 code for SSI, the CDC criteria for deep infection, and incision and débridement for infection. Three hundred sixty-one (6%) of the 5761 surgeries received an ICD-9 code for SSI within 90 days of surgery. After review of the medical records of these 361 patients, 216 (4%) met the CDC criteria for deep SSI, and 189 (3%) were taken to the operating room for irrigation and débridement within 180 days of the day of surgery. RESULTS: We found the Charlson Comorbidity Index, the duration of the operation, obesity, and posterior surgical approach were independently associated with a higher risk of infection for each of the three definitions of SSI. The influence of malnutrition, smoking, specific procedures, and specific surgeons varied by definition of infection. These elements accounted for approximately 6% of the variability in the risk of developing an infection. CONCLUSIONS: The frequency of SSI after spine surgery varied according to the definition of an infection, but the most important risk factors did not. We conclude that large database studies may be better suited for identifying risk factors than for determining absolute numbers of infections. LEVEL OF EVIDENCE: Level III, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Are Allogeneic Blood Transfusions Associated With Decreased Survival After Surgery for Long-bone Metastatic Fractures?

BACKGROUND: Previous studies have shown that perioperative blood transfusion increases cancer recurrence and decreases patient survival after resection of primary malignancies. The question arises whether this association also exists in patients with already disseminated disease undergoing surgery for metastatic long-bone fractures. PURPOSES: We sought to determine whether perioperative allogeneic blood transfusion is associated with decreased survival after operative treatment of long-bone metastatic fractures after accounting for clinical, laboratory, and treatment factors. Secondarily, we aimed to identify potential factors that are associated with decreased survival. METHODS: We included 789 patients in our retrospective study who underwent surgery at two institutions for a pathologic or impending metastatic long-bone fracture. We used multivariable Cox proportional hazards regression model analysis to assess the relationship of perioperative allogeneic blood transfusion with survival, and accounted for patient age, sex, comorbidities, BMI, tumor type, fracture type and location, presence of other bone and visceral metastases, previous radiotherapy and systemic therapy, preoperative embolization, preoperative hemoglobin level, treatment type, anesthesia time, blood loss, duration of hospital admission, year of surgery, and hospital. RESULTS: Considering transfusion as an "exposure," and comparing patients who received transfusions with those who did not, we found that blood transfusion was not associated with decreased survival after accounting for all explanatory variables (hazard ratio [HR] 1.06; 95% CI, 0.87-1.30; p = 0.57). Evaluating transfusion in terms of dose-response, we found that patients who received more transfusions had lower survival compared with those who had fewer transfusions after accounting for all explanatory variables (HR per unit of blood transfused, 1.07; 95% CI, 1.02-1.12; p = 0.005). We found that age (HR, 1.02; 95% CI, 1.01-1.02; p < 0.001), comorbidity status (HR, 1.06; 95% CI, 1.01-1.10; p = 0.014), duration of hospital stay (HR, 1.02; 95% CI 1.00-1.03; p = 0.021), tumor type (HR, 1.71; 95% CI, 1.44-2.03; p < 0.001), and visceral metastases (HR, 1.59; 95% CI, 1.34-1.88; p < 0.001) were independently associated with survival. CONCLUSION: We found that exposure to perioperative allogeneic blood transfusion does not decrease survival, with the numbers available. However, our sample size might have been insufficient to reveal a small but potentially relevant effect. Our results do suggest a dose-response relationship; patients who received more transfusions had lower survival compared with those with fewer transfusions. Risk of death increased by 7% per unit of blood transfused. LEVEL OF EVIDENCE: Level III, prognostic study.

Plate and Screw Fixation of Bicolumnar Distal Humerus Fractures: Factors Associated With Loosening or Breakage of Implants or Nonunion.

PURPOSE: To identify factors associated with reoperation for early loosening or breakage of implants or nonunion after operative treatment of AO type C distal humerus fractures. METHODS: We retrospectively analyzed 129 adult patients who had operative treatment of an isolated AO type C distal humerus fracture at 1 of 5 hospitals to determine factors associated with reoperation for early loosening or breakage of implants or nonunion. RESULTS: Within 6 months of original fixation, 16 of 129 fractures (12%) required reoperation for loosening or breakage of implants (n = 8) or nonunion (n = 8). In bivariate analyses, the Charlson comorbidity index, smoking, a coded diagnosis of obesity, diabetes mellitus, and radiographic osteoarthritis were significantly associated with reoperation for early loosening or breakage of implants or nonunion. CONCLUSIONS: With the numbers available, patient factors rather than technical factors were associated with reoperation for loosening or breakage of implants and nonunion. Because of the relative infrequency of fixation problems and nonunion, a much larger study is needed to address technical deficiencies.

Lowest reported dose area product of 2.4 Gy∗cm2 for ultra-low-dose endovascular aortic aneurysm repair of a standard infrarenal aortic aneurysm.

This is a report of successful treatment of an abdominal aortic aneurysm via standard endovascular aortic repair with an ultra-low dose (ULD) of 2.4 Gy∗cm2 using the latest imaging software in a hybrid operating room. To the best of our knowledge, no case has yet been reported achieving a successful outcome with such ULD values to date. The key factors to achieving an ULD regarding the dose area product comprise the right technology, procedural standardization, and team education and training. This case highlights the potential for reducing the radiation dose routinely for patients and staff alike, especially for operating room staff with daily radiation exposure.

A dynamic time-to-event model for prediction of acute graft-versus-host disease in patients after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Acute graft-versus-host disease (aGvHD) is a major cause of death for patients following allogeneic hematopoietic stem cell transplantation (HSCT). Effective management of moderate to severe aGvHD remains challenging despite recent advances in HSCT, emphasizing the importance of prophylaxis and risk factor identification. METHODS: In this study, we analyzed data from 1479 adults who underwent HSCT between 2005 and 2017 to investigate the effects of aGvHD prophylaxis and time-dependent risk factors on the development of grades II-IV aGvHD within 100 days post-HSCT. RESULTS: Using a dynamic longitudinal time-to-event model, we observed a non-monotonic baseline hazard overtime with a low hazard during the first few days and a maximum hazard at day 17, described by Bateman function with a mean transit time of approximately 11 days. Multivariable analysis revealed significant time-dependent effects of white blood cell counts and cyclosporine A exposure as well as static effects of female donors for male recipients, patients with matched related donors, conditioning regimen consisting of fludarabine plus total body irradiation, and patient age in recipients of grafts from related donors on the risk to develop grades II-IV aGvHD. Additionally, we found that higher cumulative hazard on day 7 after allo-HSCT are associated with an increased incidence of grades II-IV aGvHD within 100 days indicating that an individual assessment of the cumulative hazard on day 7 could potentially serve as valuable predictor for later grades II-IV aGvHD development. Using the final model, stochastic simulations were performed to explore covariate effects on the cumulative incidence over time and to estimate risk ratios. CONCLUSION: Overall, the presented model showed good descriptive and predictive performance and provides valuable insights into the interplay of multiple static and time-dependent risk factors for the prediction of aGvHD.

Soil and human health: Understanding agricultural and socio-environmental risk and resilience in the age of climate change.

Prolonged monocropping of commodity crops, such as peanuts (Arachis hypogea L.) in West Africa, typically strips nutrients from soils and may exacerbate vulnerability to insects and diseases. In this paper, we focus on aflatoxins, toxic chemicals produced by certain molds growing on moist crops, as one risk of growing importance for its negative impacts on human health, crop yields, and agricultural livelihoods and ecosystems. We link the increased prevalence of this deadly fungus to the long history of peanut monoculture, exacerbated by market liberalization and China's increased investment and export demand for peanuts, climate change, food insecurity, as well as disregard for and displacement of traditional agricultural knowledge. We use a political ecology approach to place the public health threat from aflatoxin in the context of both historical pressures for cash-crop production of peanuts and contemporary soil degradation, food insecurity, climate change precarity and changes within social and economic systems of agriculture in Senegal.

Yeast profilin complements profilin deficiency in transgenic tomato fruits and allows development of hypoallergenic tomato fruits.

Gene silencing of Lyc e 1 leads to reduced allergenicity of tomato fruits but impaired growth of transgenic tomato plants. The aim of the study was to restore growth of Lyc e 1-deficient tomato plants while retaining reduced allergenicity by simultaneous complementation of profilin deficiency by expression of nonallergenic yeast profilin. Transgenic plants were generated and tested by RT-PCR and immunoblotting; allergenicity of yeast profilin and transgenic fruits was investigated by IgE binding, basophil activation, and skin-prick tests. Lyc e 1 content of transgenic tomato fruits was <5% of that of wild-type plants, causing significantly reduced IgE antibody binding. Simultaneous coexpression of yeast profilin restored growth and biomass production almost to wild-type levels. Yeast profilin, sharing 32.6% amino acid sequence identity with Lyc e 1, displayed low IgE-binding capacity and allergenic potency. Among 16 tomato-allergic patients preselected for sensitization to Lyc e 1, none showed significant reactivity to yeast profilin. Yeast profilin did not induce mediator release, and coexpression of yeast profilin did not enhance the allergenicity of Lyc e 1-reduced fruits. Simultanous coexpression of yeast profilin allows silencing of tomato profilin and generation of viable plants with Lyc e 1-deficient tomato fruits. Therefore, a novel approach to allergen avoidance, genetically modified foods with reduced allergen accumulation, can be generated even if the allergen fulfills an essential cellular function in the plant. In summary, our findings of efficiently complementing profilin-deficient tomato plants by coexpression of low allergenic yeast profilin demonstrate the feasibility of creating low-allergenic food even if the allergen fulfills essential cellular functions.

Challenges and Pitfalls for Implementing Digital Health Solutions in Clinical Studies in Europe.

The increasing number of digital solutions developed for use in clinical health care settings is accompanied by new challenges to develop and conduct clinical studies that include eHealth technologies. Clinical study implementation plans often disregard or underestimate the necessity of additional administrative and logistic tasks required at clinical sites as well as ethical aspects to test digital solutions. Experiences made in the run-up of an observational clinical feasibility study at three international clinical sites in the framework of the MyPal project (https://mypal-project.eu/) result in recommendations to avoid delays and barriers in the planning of such prospective studies in clinical and also palliative care for increased efficiency.

Ultrasound Evaluation for Incomplete Carpal Tunnel Release.

Background: Ultrasound can provide evaluation of the anatomy of the carpal tunnel in a convenient, noninvasive office setting. This study is intended to determine the accuracy and diagnostic performance of ultrasound, used by surgeons, for the evaluation of completeness of carpal tunnel release (CTR). Methods: Ten cadaver arms underwent randomized sectioning of 0%, 25%, 50%, 75%, or 100% of the transverse carpal ligament. Following a brief training session, a blinded observer used ultrasound to evaluate the percentage of the transverse carpal ligament release. The release amount was then confirmed with an open exposure of the transverse carpal ligament. Results: Cronbach α and Pearson correlation coefficients were 0.92 and 0.87, demonstrating excellent reliability and validity of the technique. Diagnostic performance including sensitivity, specificity, positive predictive value, and negative predictive value was 100%, 75%, 86%, and 100%, respectively, for the diagnosis of incomplete release of the transverse carpal ligament by a novice sonographer orthopedic surgeon. Conclusions: The ultrasound is a highly accurate tool for the diagnosis of incomplete transverse carpal ligament release and requires a minimal amount of training to use for this purpose. It provides a rapid means of diagnosing incomplete release of the transverse carpal ligament following CTR.

Coronatine Gene Expression In Vitro and In Planta, and Protein Accumulation During Temperature Downshift in Pseudomonas syringae.

The plant pathogenic bacterium Pseudomonas syringae PG4180 synthesizes high levels of the phytotoxin coronatine (COR) at the virulence-promoting temperature of 18 °C, but negligible amounts at 28 °C. Temperature-dependent COR gene expression is regulated by a modified two-component system, consisting of a response regulator, CorR, the histidine protein kinase CorS, and a third component, termed CorP. We analyzed at transcriptional and translational levels the expression of corS and the cma operon involved in COR biosynthesis after a temperature downshift from 28 to 18 °C. Expression of cma was induced within 20 min and increased steadily whereas corS expression was only slightly temperature-dependent. Accumulation of CmaB correlated with accumulation of cma mRNA. However, cma transcription was suppressed by inhibition of de novo protein biosynthesis. A transcriptional fusion of the cma promoter to a promoterless egfp gene was used to monitor the cma expression in vitro and in planta. A steady induction of cma::egfp by temperature downshift was observed in both environments. The results indicate that PG4180 responds to a temperature decrease with COR gene expression. However, COR gene expression and protein biosynthesis increased steadily, possibly reflecting adaptation to long-term rather than rapid temperature changes.

Social impacts of large dam projects: a comparison of international case studies and implications for best practice.

This paper applies the tool of social impact assessment (SIA) to understand the effects of large dam projects on human communities. We draw upon data from two recent SIA projects: the Lesotho Highlands Water Project in Southern Africa, and the Manwan Dam, located on the upper Mekong River in southwestern China. These two cases allow us to examine the social impacts of large dam projects through time and across various geographical scales. We focus on a range of social impacts common to many large-scale dam projects, including: the migration and resettlement of people near the dam sites; changes in the rural economy and employment structure; effects on infrastructure and housing; impacts on non-material or cultural aspects of life; and impacts on community health and gender relations. By identifying potential impacts in advance of a large dam project, agencies and policymakers can make better decisions about which interventions should be undertaken, and how. We conclude our analysis with an overview of lessons learned from the case studies and suggestions for best practice in assessing the social impacts of large dams. Conducting proper social impact assessments can help to promote development strategies that address the most important concerns for local populations, enhancing the long-term sustainability of dam projects.

Benchmarking Wilms' tumor in multisequence MRI data: why does current clinical practice fail? Which popular segmentation algorithms perform well?

Wilms' tumor is one of the most frequent malignant solid tumors in childhood. Accurate segmentation of tumor tissue is a key step during therapy and treatment planning. Since it is difficult to obtain a comprehensive set of tumor data of children, there is no benchmark so far allowing evaluation of the quality of human or computer-based segmentations. The contributions in our paper are threefold: (i) we present the first heterogeneous Wilms' tumor benchmark data set. It contains multisequence MRI data sets before and after chemotherapy, along with ground truth annotation, approximated based on the consensus of five human experts. (ii) We analyze human expert annotations and interrater variability, finding that the current clinical practice of determining tumor volume is inaccurate and that manual annotations after chemotherapy may differ substantially. (iii) We evaluate six computer-based segmentation methods, ranging from classical approaches to recent deep-learning techniques. We show that the best ones offer a quality comparable to human expert annotations.