Strong Evidence for

The boundaries of the chart of nuclides contain exotic isotopes that possess extreme proton-to-neutron asymmetries. Here we report on strong evidence of ^{9}N, one of the most exotic proton-rich isotopes where more than one half of its constitute nucleons are unbound. With seven protons and two neutrons, this extremely proton-rich system would represent the first-known example of a ground-state five-proton emitter. The invariant-mass spectrum of its decay products can be fit with two peaks whose energies are consistent with the theoretical predictions of an open-quantum-system approach; however, we cannot rule out the possibility that only a single resonancelike peak is present in the spectrum.

Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial.

BACKGROUND: STAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naïve prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients. METHODS: We randomly allocated patients in 2 : 1 ratio to standard-of-care (SOC; control group) or SOC + docetaxel. Metastatic disease burden was categorised using retrospectively-collected baseline staging scans where available. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional. RESULTS: Between 05 October 2005 and 31 March 2013, 1086 M1 patients were randomised to receive SOC (n = 724) or SOC + docetaxel (n = 362). Metastatic burden was assessable for 830/1086 (76%) patients; 362 (44%) had low and 468 (56%) high metastatic burden. Median follow-up was 78.2 months. There were 494 deaths on SOC (41% more than the previous report). There was good evidence of benefit of docetaxel over SOC on OS (HR = 0.81, 95% CI 0.69-0.95, P = 0.009) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P = 0.827). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR = 0.66, 95% CI 0.57-0.76, P < 0.001) and progression-free survival (HR = 0.69, 95% CI 0.59-0.81, P < 0.001) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P > 0.5 in each case). There was no evidence that docetaxel resulted in late toxicity compared with SOC: after 1 year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1 year without prior progression). CONCLUSIONS: The clinically significant benefit in survival for upfront docetaxel persists at longer follow-up, with no evidence that benefit differed by metastatic burden. We advocate that upfront docetaxel is considered for metastatic hormone naïve prostate cancer patients regardless of metastatic burden.

Front and pulse solutions for a system of reaction-diffusion equations with degenerate source terms.

Motivated by several biological models such as the SIS model from epidemiology and the Tuckwell-Miura model describing cortical spreading depression, we investigate the types of wave solutions that can exist for reaction-diffusion systems of two equations in which the reaction terms are degenerate in the sense that they are linearly dependent. In particular, we show that there are surprising differences between the types of waves that occur in a single reaction-diffusion equation and the types of waves that occur in a degenerate system of two equations. Importantly, and in contrast to previously published results, we demonstrate that nonstationary pulse solutions can exist for a degenerate system of two equations but cannot exist for a single reaction-diffusion equation. We show that this has important consequences for the minimal model that can generate the types of waves observed in cortical spreading depression. On the other hand, stationary fronts can exist for both single reaction-diffusion equations and degenerate systems. However, for degenerate systems, such solutions cannot be accessed when perturbing a uniform rest state with a localized perturbation unless the diffusion coefficients of the two species are equal. We also give an explicit condition on the source term in a degenerate reaction-diffusion system that guarantees the existence of nonstationary and stationary pulse and front solutions. We use this approach to provide several examples of reaction terms that have analytical pulse and front solutions. We also show that the case in which one species cannot diffuse is singular in the sense that the degenerate reaction-diffusion system can admit infinite families of stationary piecewise constant solutions. We further show how such solutions can be accessed by perturbing a constant rest state with a localized continuous disturbance.

A national survey of current practices of preparation and management of radical prostate radiotherapy patients during treatment.

AIMS: Radiotherapy is an important radical treatment for prostate cancer patients with services continually evolving. This survey aims to gain an insight in to the variation of radiotherapy practices in the UK, focussing on pre-treatment preparations, on-treatment review and management of radical prostate cancer patients undergoing radiotherapy. To our knowledge this is the first survey reported focussing on prostate radiotherapy practices with responses from a mix of health professionals. MATERIALS AND METHODS: A national survey was designed based on current known practices in supportive care and management of prostate cancer patients. The survey was distributed to lead radiotherapy personnel in radiotherapy services across the UK with a 77% response rate (n = 54). RESULTS: Pre-treatment protocols were mandated in the majority of departments. Use of bladder filling (98%) and bowel emptying (66%) were frequently deployed. Bowel preparation varied between use of laxatives (13%) or enemas (41%) to achieve consistency. On-treatment reviews were carried out by a mix of health professionals; most commonly shared between oncologists and radiographers (20%). Radiographers reviewing patients were independent prescribers in 22% of departments. Toxicity grading tools were not used by almost half of departments (47%) either at baseline and/or on-treatment reviews. Written information about follow-up was given to patients towards the end of their radiotherapy; however, fewer departments included the length of hormone duration (13%). CONCLUSION: This survey has demonstrated variations in practice exist across the UK. These variations suggest that important questions about the best methods for treatment accuracy and patient management need to be established through further research.

Comparison of measurements of the glenopolar angle in 3D CT reconstructions of the scapula and 2D plain radiographic views.

AIMS: The aim of this study was to analyse the effect of altered viewing perspectives on the measurement of the glenopolar angle (GPA) and the differences between these measurements made on 3D CT reconstructions and anteroposterior (AP) scapular view radiographs. MATERIALS AND METHODS: The influence of the viewing perspective on the GPA was assessed, as were the differences in the measurements of the GPA between 3D CT reconstructions and AP scapular view radiographs in 68 cadaveric scapulae. RESULTS: The median GPA in 3D reconstructions and AP scapular views were 42.7° (95% confidence intervals (CI), 42.0° to 43.5°) and 41.3° (95% CI 40.4° to 42.0°) respectively (p < 0.001). All but five of 20 malpositions demonstrated a significant difference in GPA compared with the respective AP scapular view (p ≤ 0.005). The GPA was most susceptible to malposition in retroversion/anteversion. Inter- and intra-observer reliability for all measurements of the GPA was excellent for 3D CT reconstructions (intraclass correlation (ICC) 0.93 (95% CI 0.87 to 0.96) and 0.94 (95% CI 0.89 to 0.97), respectively) and higher than on AP scapular radiographs (p < 0.001). The intra- and inter-observer reliability was excellent in AP scapular views and malpositions in extension/flexion (ICC ≥ 0.84) but tended to decrease with increasing viewing angle in retroversion/anteversion. CONCLUSION: These data suggest that 3D reconstructions are more reproducible than AP scapular radiographs in the assessment of the GPA and should be used to compare data in different studies, to predict outcome, define malunion, and act as an indication for surgery in patients with a scapular fracture. Cite this article: Bone Joint J 2016;98-B:1510-16.

Decline in Decreased Cephalosporin Susceptibility and Increase in Azithromycin Resistance in Neisseria gonorrhoeae, Canada.

Antimicrobial resistance profiles were determined for Neisseria gonorrhoeae strains isolated in Canada during 2010-2014. The proportion of isolates with decreased susceptibility to cephalosporins declined significantly between 2011 and 2014, whereas azithromycin resistance increased significantly during that period. Continued surveillance of antimicrobial drug susceptibilities is imperative to inform treatment guidelines.

Impact of a social media campaign targeting men who have sex with men during an outbreak of syphilis in Winnipeg, Canada.

BACKGROUND: The city of Winnipeg has experienced a surge of infectious syphilis cases since the fall of 2012, concentrated among men who have sex with men (MSM) and who use social media technologies-including phone applications-to meet sexual contacts. OBJECTIVE: To evaluate the acceptability, cost and effectiveness of a campaign promoting syphilis testing on popular websites and applications used by MSM in the Winnipeg Health Region (WHR). METHODS: The Winnipeg Regional Health Authority developed a campaign in March 2014 highlighting the syphilis outbreak and the importance of seeking testing. Over one month, advertisements appeared on four web-platforms: Grindr, Facebook, Squirt and the Gay Ad Network. When clicked, ads would direct the user to an information website. Acceptability was assessed using the number of 'clicks' elicited by advertisements on each platform. The cost of each platform's run of advertisements was compared to the number clicks elicited to produce a cost-per-click ratio for each platform. Effectiveness was assessed by comparing the number of syphilis tests ordered for male residents of the Winnipeg Health Region in the seven-week period before and after the campaign, as well as to the same time periods in 2012 and 2013. RESULTS: Out of 800,000 appearances purchased, the advertisements elicited 2,166 clicks, suggesting good acceptability. Grindr and Squirt advertisements had a better cost-per-click ratio than Facebook or the Gay Ad Network. There was no significant difference in testing before (2,049 tests) versus after (2,025 tests) the campaign and these findings were similar to testing trends in 2012 and 2013. CONCLUSION: Although this web-based campaign showed good acceptability and low cost, it did not appear to increase syphilis testing. This may be due to a poor campaign design; it also suggests that an education campaign alone may be insufficient to change behaviour.

Molecular Assay for Detection of Ciprofloxacin Resistance in Neisseria gonorrhoeae Isolates from Cultures and Clinical Nucleic Acid Amplification Test Specimens.

We developed a real-time PCR assay to detect single nucleotide polymorphisms associated with ciprofloxacin resistance in specimens submitted for nucleic acid amplification testing (NAAT). All three single nucleotide polymorphism (SNP) targets produced high sensitivity and specificity values. The presence of ≥2 SNPs was sufficient to predict ciprofloxacin resistance in an organism.

Molecular Assay for Detection of Genetic Markers Associated with Decreased Susceptibility to Cephalosporins in Neisseria gonorrhoeae.

The incidence of antimicrobial-resistant Neisseria gonorrhoeae continues to rise in Canada; however, antimicrobial resistance data are lacking for approximately 70% of gonorrhea infections that are diagnosed directly from clinical specimens by nucleic acid amplification tests (NAATs). We developed a molecular assay for surveillance use to detect mutations in genes associated with decreased susceptibility to cephalosporins that can be applied to both culture isolates and clinical samples. Real-time PCR assays were developed to detect single nucleotide polymorphisms (SNPs) in ponA, mtrR, penA, porB, and one N. gonorrhoeae-specific marker (porA). We tested the real-time PCR assay with 252 gonococcal isolates, 50 nongonococcal isolates, 24 N. gonorrhoeae-negative NAAT specimens, and 34 N. gonorrhoeae-positive NAAT specimens. Twenty-four of the N. gonorrhoeae-positive NAAT specimens had matched culture isolates. Assay results were confirmed by comparison with whole-genome sequencing data. For 252 N. gonorrhoeae strains, the agreement between the DNA sequence and real-time PCR was 100% for porA, ponA, and penA, 99.6% for mtrR, and 95.2% for porB. The presence of ≥2 SNPs correlated with decreased susceptibility to ceftriaxone (sensitivities of >98%) and cefixime (sensitivities of >96%). Of 24 NAAT specimens with matched cultures, the agreement between the DNA sequence and real-time PCR was 100% for porB, 95.8% for ponA and mtrR, and 91.7% for penA. We demonstrated the utility of a real-time PCR assay for sensitive detection of known markers for the decreased susceptibility to cephalosporins in N. gonorrhoeae. Preliminary results with clinical NAAT specimens were also promising, as they correlated well with bacterial culture results.

Patient-reported outcomes and health-related quality of life in prostate cancer treated with a single fraction of high dose rate brachytherapy combined with hypofractionated external beam radiotherapy.

AIMS: High dose rate (HDR) brachytherapy offers a highly conformal approach to radiotherapy delivery, enabling dose escalation. We report our experience using a combined HDR boost and external beam radiotherapy (EBRT) approach and its associated toxicity and effect on quality of life. MATERIALS AND METHODS: Patients with intermediate- or high-risk prostate cancer were treated with a single fraction HDR boost and EBRT between July 2008 and March 2010. Patient-reported toxicity data were collected at baseline and regular intervals after radiotherapy using International Prostate Symptom Score and Late Effects in Normal Tissues-Subjective, Objective, Management and Analytic scales (LENT-SOMA) questionnaires; health-related quality of life data were captured by the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. RESULTS: Ninety-five patients received an HDR boost of 12.5 Gy followed by EBRT delivered as 37.5 Gy in 15 fractions over 3 weeks. The International Prostate Symptom Score peaked 6 weeks after radiotherapy (median value: 9). The LENT-SOMA bladder/urethra mean baseline score was 0.35 and peaked 6 weeks after radiotherapy (mean = 0.59). Difficulties with urinary flow and frequency were the most common reported symptoms. LENT-SOMA rectum/bowel mean scores at baseline were 0.24 and peaked after 6 months (mean = 0.37). Bowel urgency was the most common reported toxicity. EPIC urinary scores returned to baseline values at 6 months and bowel median scores recovered after 24 months. There were no statistically significant associations between patient or dosimetric parameters and patient-reported outcomes. CONCLUSION: A combined HDR boost and hypofractionated EBRT regimen offers a well-tolerated method of dose escalation with acceptable levels of patient-reported toxicity.

Effect of the CT table strap on radiation exposure and image quality during cervical spine CT.

BACKGROUND AND PURPOSE: The CT table strap may impair shoulder lowering during cervical spine CT. The purpose of this investigation was to evaluate the effect of the CT table strap on radiation exposure and image quality during CT of the cervical spine. MATERIALS AND METHODS: Patients undergoing cervical spine CT were prospectively randomized to having the CT table strap placed around the torso and arms (control group) or around the torso only (intervention group). Radiation exposure, shoulder position, and image quality were evaluated. Potential confounders, including neck diameter and scan length, were also assessed. RESULTS: Fifty-eight patients were enrolled and randomized, and 51 subjects were included in the final study population. There was a 21% decrease in radiation exposure in the intervention group compared with the control group (mean dose-length product, 540 ± 152 versus 686 ± 200 mGy × cm, P = .005). Subjects in the intervention group achieved shoulder lowering of an average of >1 vertebral body lower than the control group (mean shoulder level, 7.7 ± 1.3 versus 6.5 ± 1.3, P = .001). Subjective image quality, determined by the lowest level of spinal cord visibility, was also better in the intervention group (mean cord visibility level, 6.9 ± 1.3 versus 5.9 ± 1.3, P = .006). No differences in neck diameter (P = .28) or scan length (P = .55) were observed between groups. CONCLUSIONS: The CT table strap inhibits shoulder lowering during CT of the cervical spine. Placement of the patient's arms outside the CT table strap results in decreased radiation exposure and increased image quality compared with patients whose arms are placed inside the strap.

Differential susceptibility of invasive Haemophilus influenzae serotype a and serotype b to ampicillin and other commonly prescribed antibiotics.

UNLABELLED: Haemophilus influenzae serotype a (Hia) has become an important pathogen in the post-H. influenzae serotype b (Hib) vaccine era. Antibiotic resistance in H. influenzae is a global phenomenon, but few studies have looked at antibiotic resistance profiles with regard to serotype. Invasive Hia (n = 157), noninvasive Hia (n = 2) and invasive Hib (n = 42) collected over the last two decades from three Canadian Provinces were examined for resistance to several commonly prescribed antibiotics, and sequence types (STs) were determined by MLST. Only 1·9% of Hia showed antibiotic resistance, while 31% of Hib were resistant to one or more antibiotic. Resistance to ampicillin, sulfamethoxazole-trimethoprim, chloramphenicol and tetracycline was observed, with ß-lactamase-mediated ampicillin resistance being the most common. Nine STs were identified for Hia with 7 STs belonging to the same clonal complex. Ten STs were observed in Hib strains, and all of them belonged to a single clonal complex. A possible correlation between sequence type and ampicillin resistance was observed for Hib, while no correlations were observed for Hia. SIGNIFICANCE AND IMPACT OF THE STUDY: Despite H. influenzae serotype b (Hib) vaccine programs, invasive disease due to Hib still exists in Canada and is either second or third most common behind nontypeable and/or serotype a (Hia). Many previous studies on antibiotic resistance have focussed on respiratory isolates, and few have looked at resistance with regard to serotype. This study analysed antibiotic resistance in invasive Hia and Hib collected over 20 years from three provinces, and results found that significantly more Hib showed resistance compared to Hia. This provides a small snapshot of H. influenzae disease in Canada and highlights the importance to continually monitor antibiotic resistance profiles.

Evaluation of a new chromogenic agar medium for detection of Shiga toxin-producing Escherichia coli (STEC) and relative prevalences of O157 and non-O157 STEC in Manitoba, Canada.

This study assesses the detection performance of CHROMagar STEC medium relative to a reference cytotoxin assay and describes the current relative prevalence of O157 and non-O157 Shiga toxin-producing Escherichia coli (STEC) serotypes within the province of Manitoba, Canada. Over a 10-month period, 205 nonfrozen routine stool submissions to Cadham Provincial Laboratory (CPL) were used to assess the performance of CHROMagar STEC. Of the 205 stools, 14 were identified as true positives by a cytotoxin assay, with resultant CHROMagar STEC sensitivity, specificity, and positive predictive and negative predictive values of 85.7%, 95.8%, 60.0%, and 98.9%, respectively. Using a separate panel of 111 STEC strains, CHROMagar STEC was shown to support the growth of 96 (86.5%) isolates. To assess relative prevalence, attempts were made to isolate by any means all STEC strains identified at CPL over a 17-month period. Of 49 isolates (representing 86.0% of all STEC infections detected), only 28.6% were O157 STEC strains. Of the 35 non-O157 STEC strains, 29 were subjected to further molecular analysis. In contrast to earlier results from our area, carriage of stx(2) appears to have increased. Overall, although CHROMagar STEC is not recommended as a primary screen, our results indicate that it is an effective supplemental medium for the isolation of probable STEC strains. Increased isolation of these serotypes is warranted to better understand their prevalence, clinical characteristics, and epidemiology and aid in the development or enhancement of food safety control programs targeting all STEC serotypes.

Perianal actinomycosis: a case study of this rare infection associated with nicorandil usage.

Perianal actinomycosis infection is a very rare occurrence and is challenging to diagnose. Nicorandil is a potassium channel agonist, which is used in the treatment of ischaemic heart disease. Its usage is associated with perianal ulceration and delayed surgical wound healing. We report a case of actinomycosis complicating a chronic perianal ulcer, which was associated with long-term nicorandil usage. It raised the suspicion of malignancy and required over six months of antimicrobial treatment to achieve satisfactory healing. Perianal actinomycosis results in chronic infection which spreads across tissue planes and can resemble an ulcerated malignancy. Nicorandil usage can result in perianal ulceration and produces conditions which are conducive to actinomycosis infection. In such cases, nicorandil therapy should be discontinued, if possible, and long-term systemic antibiotics form the mainstay of treatment.

Proximal humeral fractures with a severe varus deformity treated by fixation with a locking plate.

We treated 47 patients with a mean age of 57 years (22 to 88) who had a proximal humeral fracture in which there was a severe varus deformity, using a standard operative protocol of anatomical reduction, fixation with a locking plate and supplementation by structural allografts in unstable fractures. The functional and radiological outcomes were reviewed. At two years after operation the median Constant score was 86 points and the median Disabilities of the Arm, Shoulder and Hand score 17 points. Seven of the patients underwent further surgery, two for failure of fixation, three for dysfunction of the rotator cuff, and two for shoulder stiffness. The two cases of failure of fixation were attributable to violation of the operative protocol. In the 46 patients who retained their humeral head, all the fractures healed within the first year, with no sign of collapse or narrowing of the joint space. Longer follow-up will be required to confirm whether these initially satisfactory results are maintained.

10mM glucosamine prevents activation of proADAMTS5 (aggrecanase-2) in transfected cells by interference with post-translational modification of furin.

OBJECTIVE: Glucosamine has been previously shown to suppress cartilage aggrecan catabolism in explant cultures. We determined the effect of glucosamine on ADAMTS5 (a disintegrin-like and metalloprotease domain (reprolysin type) with thrombospondin type-1 motifs 5), a major aggrecanase in osteoarthritis, and investigated a potential mechanism underlying the observed effects. DESIGN: HEK293F and CHO-K1 cells transiently transfected with ADAMTS5 cDNA were treated with glucosamine or the related hexosamine mannosamine. Glucosamine effects on FURIN transcription were determined by quantitative RT-PCR. Effects on furin-mediated processing of ADAMTS5 zymogen, and aggrecan processing by glucosamine-treated cells, were determined by western blotting. Post-translational modification of furin and N-glycan deficient furin mutants generated by site-directed mutagenesis was analyzed by western blotting, and the mutants were evaluated for their ADAMTS5 processing ability in furin-deficient CHO-RPE.40 cells. RESULTS: Ten mM glucosamine and 5-10mM mannosamine reduced excision of the ADAMTS5 propeptide, indicating interference with the propeptide excision mechanism, although mannosamine compromised cell viability at these doses. Although glucosamine had no effect on furin mRNA levels, western blot of furin from glucosamine-treated cells suggested altered post-translational modification. Glucosamine treatment led to decreased glycosylation of cellular furin, with reduced furin autoactivation as the consequence. Recombinant furin treated with peptide N-glycanase F had reduced activity against a synthetic peptide substrate. Indeed, site-directed mutagenesis of two furin N-glycosylation sites, Asn(387) and Asn(440), abrogated furin activation and this mutant was unable to rescue ADAMTS5 processing in furin-deficient cells. CONCLUSIONS: Ten mM glucosamine reduces excision of the ADAMTS5 propeptide via interference with post-translational modification of furin and leads to reduced aggrecanase activity of ADAMTS5.

Contribution of a real depth distance stereoacuity test to clinical management.

Measurement of Stereopsis forms an important part of the clinical assessment of patients with disorders of ocular motility. The introduction of a real depth distance stereoacuity test (FD2) was evaluated in clinical practice and to what extent the introduction affected clinical management. Seventy-three patients under evaluation before and following the introduction of the test were included. Combined thresholds were measured at near using the Frisby and TNO test and at distance using the FD2. Fifty healthy controls were included. Forty-five patients demonstrated Stereopsis using the FD2 and 23 of these had a change in their management based in part on their responses using the FD2. Patients with evidence of Stereopsis using the FD2 were significantly more likely to have change in their management than expected from the whole sample (P = .02). The introduction of a real depth distance stereoacuity test into clinical practice contributed to a change in management when used in conjunction with other tests. The usefulness of the FD2 is limited by its range at 6 m. Use at closer distances necessitates the calculation of binocular threshold from the combined and monocular threshold.

Treatment of saline, acidic, metal-contaminated groundwater from the Western Australian Wheatbelt.

Managing acidic, metal-containing saline ground and drainage waters in the Wheatbelt of Western Australia is an environmental and economic challenge. Sulfate-reducing fluidised bed bioreactors are shown to be technically capable of treating high salt, low pH, metal containing waters from the town of Narembeen in the Wheatbelt so as to reduce acidity and to remove most of the undesirable metal contaminants. The hydraulic residence time (HRT) limit for a stable process with groundwater from the region of Narembeen was >16 hours. The maximal rate of sulfate reduction in the laboratory system treating Narembeen groundwater was similar to rates observed in comparable applications of the process at other sites, ca. 3 g sulfate (L-reactor)(-1) day(-1). Salts that are relatively free of metal contaminants can be produced from water that has been treated by the sulfate-reducing fluidised bed bioreactor. It is unlikely that metal precipitates, captured from Wheatbelt waters by the process, would be of economic value. If sulfate-reducing fluidised bed reactors were considered technologically appropriate at larger scale, the decision to use them would be based on the necessity to take action, the comparative effectiveness of competing technologies, and the relative costs of competing technologies.