Management of chemotherapy hypersensitivity reactions and desensitization: An SGO clinical practice statement.

OBJECTIVE: The goal of this practice statement is to help members and their multidisciplinary teams recognize infusion reactions and hypersensitivity reactions in the clinical setting. It will provide recommendations to help guide response to reactions and desensitization when appropriate, to promote safe use of chemotherapeutic agents among all providers in the delivery process. METHODS: A multi-disciplinary team of healthcare professionals from the Society of Gynecologic Oncology Education Committee collaborated to review peer reviewed literature and guidelines to develop a practice statement on the management of chemotherapy hypersensitivity reactions and desensitization regimens. RESULTS: There is always potential for a patient to have a reaction to any medication, with both infusion reactions and hypersensitivity reactions potentially occurring in the treatment of gynecologic cancers. Premedication to prevent reactions should be given at least prior to infusion for regimens that include the most common agents associated with reactions. At the time when reaction is occurring it might be difficult to distinguish between an infusion reaction versus true hypersensitivity given the similarities in signs and symptoms, therefore it is important that orders to manage reactions be included in every chemotherapy order set so the infusion nurse can provide immediate interventions while waiting for the provider to arrive to assess the patient. Desensitization is a potential option to allow the patient to continue to receive the offending agent. While a variety of desensitization regimens have been presented in the literature, the goal is to minimize steps and variability to decrease opportunity for errors during chemotherapy preparation or administration. CONCLUSION: Incorporating a review of the literature and clinical experience from the SGO Education Committee, this paper provides an overview of current approaches for prevention and management of reactions to commonly used chemotherapy agents for gynecologic cancers.

Effect of neuromuscular reversal with neostigmine/glycopyrrolate versus sugammadex on postoperative ileus following colorectal surgery.

BACKGROUND: Postoperative ileus (POI) is a common complication following colorectal surgery and is mediated in part by the cholinergic anti-inflammatory pathway (CAIP). Neostigmine (acetylcholinesterase inhibitor), co-administered with glycopyrrolate, is frequently given for neuromuscular reversal before tracheal extubation and modulates the CAIP. An alternative reversal agent, sugammadex (selective rocuronium or vecuronium binder), acts independently from the CAIP. The aim of our study was to assess the impact of neuromuscular reversal agents used during anaesthesia on gastrointestinal recovery. METHODS: Three hundred thirty-five patients undergoing elective colorectal surgery at the Royal Adelaide Hospital between January 2019 and December 2021 were retrospectively included. The primary outcome was GI-2, a validated composite measure of time to diet tolerance and passage of stool. Demographics, 30-day complications and length of stay were collected. Univariate and multivariate analyses were performed. RESULTS: Two hundred twenty-four (66.9%) patients (129 [57.6%] males and 95 [42.4%] females, median age 64 [19-90] years) received neostigmine/glycopyrrolate and 111 (33.1%) received sugammadex (62 [55.9%] males and 49 [44.1%] females, median age 67 [18-94] years). Sugammadex patients achieved GI-2 sooner after surgery (median 3 (0-10) vs. 3 (0-12) days, p = 0.036), and reduced time to first stool (median 2 (0-10) vs. 3 (0-12) days, p = 0.035). Rates of POI, complications and length of stay were similar. On univariate analysis, POI was associated with smoking history, previous abdominal surgery, colostomy formation, increased opioid use and postoperative hypokalaemia (p < 0.05). POI was associated with increased complications, including anastomotic leak and prolonged hospital stay (p < 0.001). On multivariate analysis, neostigmine, bowel anastomoses and increased postoperative opioid use (p < 0.05) remained predictive of time to GI-2. CONCLUSIONS: Patients who received sugammadex had a reduced time to achieving first stool and GI-2. Neostigmine use, bowel anastomoses and postoperative opioid use were associated with delayed time to achieving GI-2.

Group B Streptococcus (GBS) colonization is dynamic over time, whilst GBS capsular polysaccharides-specific antibody remains stable.

Group B Streptococcus (GBS) is a leading cause of adverse pregnancy outcomes due to invasive infection. This study investigated longitudinal variation in GBS rectovaginal colonization, serum and vaginal GBS capsular polysaccharide (CPS)-specific antibody levels. Non-pregnant women were recruited in the UK and were sampled every 2 weeks over a 12-week period. GBS isolates were taken from recto-vaginal swabs and serotyped by polymerase chain reaction. Serum and vaginal immunoglobulin G (IgG) and nasal immunoglobulin A (IgA) specific to CPS were measured by Luminex, and total IgG/A by ELISA. Seventy women were enrolled, of median age 26. Out of the 66 participants who completed at least three visits: 14/47 (29.8%) women that were GBS negative at screening became positive in follow-up visits and 16/19 (84.2%) women who were GBS positive at screening became negative. There was 50% probability of becoming negative 36 days after the first positive swab. The rate of detectable GBS carriage fluctuated over time, although serum, vaginal, and nasal CPS-specific antibody levels remained constant. Levels of CPS-specific antibodies were higher in the serum of individuals colonized with GBS than in non-colonized, but similar in the vaginal and nasal mucosa. We found correlations between antibody levels in serum and the vaginal and nasal mucosa. Our study demonstrates the feasibility of elution methods to retrieve vaginal and nasal antibodies, and the optimization of immunoassays to measure GBS-CPS-specific antibodies. The difference between the dynamics of colonization and antibody response is interesting and further investigation is required for vaccine development.

Computed tomographic and clinical features of pulmonary veno-occlusive disease: raising the radiologist's awareness.

Pulmonary veno-occlusive disease (PVOD) is a rare subtype of pulmonary arterial hypertension (PAH) characterised by preferential remodelling of the pulmonary venules. Differentiation from other subtypes of PAH is essential as the management can differ significantly; for example, initiation of vasodilator therapy may cause fatal pulmonary oedema in a patient with PVOD misdiagnosed with idiopathic PAH. PVOD also carries a substantially worse prognosis. Lung biopsy is required for definitive diagnosis, but this is hazardous, and ideally, should be avoided in pulmonary hypertension. Computed tomography (CT) may suggest the diagnosis, directing the patient towards specialist review. Potential distinguishing CT features between PVOD and other subtypes of PAH include interlobular septal thickening, mediastinal lymphadenopathy, and centrilobular ground-glass opacities. No evidence-based medical therapy exists for PVOD at present and lung transplantation remains the definitive treatment for eligible patients. Therefore, early radiological identification of this challenging diagnosis facilitates timely referral for transplant.

[Erythroderma revealing IPEX syndrome]. / Érythrodermie révélatrice d'un syndrome IPEX.

BACKGROUND: Primary immunodeficiencies are rare and frequently life-threatening conditions in the first year of life. They may present with isolated skin manifestations and the absence of other clinical signs may delay diagnosis and management of the disease. Herein we describe a case of IPEX syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked syndrome) that illustrates this situation. PATIENTS AND METHODS: A 2.5-month-old boy was seen with a psoriasiform eruption. Despite applications of topical steroids, skin lesions progressed to severe exfoliative ichtyosiform erythroderma. A skin biopsy showed keratinocyte necrosis with a dense, epidermotropic, lymphocytic CD8+ infiltrate. The infant presented increased serum IgE and eosinophilia. He developed an enteropathy with severe and profuse diarrhea, septicemia and hypovolemic shock that led to sudden cardiac arrest. DNA analysis revealed a mutation in the FOXP3 gene, confirming IPEX syndrome. A favorable outcome was achieved following allogeneic bone marrow transplant. DISCUSSION: IPEX syndrome is characterized by early secretory enteropathy with profuse diarrhea, dermatitis and diabetes mellitus. Onset usually occurs within the first weeks or months of life, and the natural course of the disease is often lethal. Cutaneous manifestations appear to be mostly eczematiform, psoriasiform or ichthyosiform. These may be the first sign of the disease and a common inflammatory skin disorder may be wrongly diagnosed. The severity of the lesions and their limited response to topical steroids should alert the clinician. CONCLUSION: The early onset of severe cutaneous manifestations with persistent lesions and poor response to topical steroids should lead to an early skin biopsy. If histopathological changes show a cytotoxic lymphocytic infiltrate with keratinocyte necrosis, a diagnosis of primary immunodeficiency must be considered enabling rapid intitation of specific management.

Understanding the Factors that Influence Perceptions of Post-Wildfire Landscape Recovery Across 25 Wildfires in the Northwestern United States.

Disturbances such as wildfire are important features of forested landscapes. The trajectory of changes following wildfires (often referred to as landscape recovery) continues to be an important research topic among ecologists and wildfire scientists. However, the landscape recovery process also has important social dimensions that may or may not correspond to ecological or biophysical perspectives. Perceptions of landscape recovery may affect people's attitudes and behaviors related to forest and wildfire management. We explored the variables that influence people's perceptions of landscape recovery across 25 fires that occurred in 2011 or 2012 in the United States of Washington, Oregon, Idaho, and Montana and that represented a range of fire behavior characteristics and landscape impacts. Residents near each of the 25 fires were randomly selected to receive questionnaires about their experiences with the nearby fire, including perceived impacts and how the landscape had recovered since the fire. People generally perceived landscapes as recovering, even though only one to two years had passed. Regression analysis suggested that perceptions of landscape recovery were positively related to stronger beliefs about the ecological role of fire and negatively related to loss of landscape attachment, concern about erosion, increasing distance from the fire perimeter, and longer lasting fires. Hierarchical linear modeling (HLM) analysis indicated that the above relationships were largely consistent across fires. These findings highlight that perceptions of post-fire landscape recovery are influenced by more than vegetation changes and include emotional and cognitive factors. We discuss the management implications of these findings.

Comparative genomic identification and validation of ß-defensin genes in the Ovis aries genome.

BACKGROUND: ß-defensins are small, cationic, antimicrobial peptides found in species across the plant and animal kingdoms. In addition to microbiocidal activity, roles in immunity as well as reproduction have more recently been documented. ß-defensin genes in Ovis aries (domestic sheep) have been poorly annotated, having been identified only by automatic gene prediction algorithms. The objective of this study was to use a comparative genomics approach to identify and characterise the ß-defensin gene repertoire in sheep using the bovine genome as the primary reference. RESULTS: All 57 currently predicted bovine ß-defensin genes were used to find orthologous sequences in the most recent version of the sheep genome (OAR v4.0). Forty three genes were found to have close genomic matches (>70% similarity) between sheep and cattle. The orthologous genes were located in four clusters across the genome, with 4 genes on chromosome 2, 19 genes on chromosome 13, 5 genes on chromosome 20 and 15 genes on chromosome 26. Conserved gene order for the ß-defensin genes was apparent in the two smaller clusters, although gene order was reversed on chromosome 2, suggesting an inversion between sheep and cattle. Complete conservation of gene order was also observed for chromosome 13 ß-defensin orthologs. More structural differences were apparent between chromosome 26 genes and the orthologous region in the bovine reference genome, which is known to be copy-number variable. In this cluster, the Defensin-beta 1 (DEFB1) gene matched to eleven Bovine Neutrophil beta-Defensin (BNBD) genes on chromosome 27 with almost uniform similarity, as well as to tracheal, enteric and lingual anti-microbial peptides (TAP, EAP and LAP), suggesting that annotation of the bovine reference sequence is still incomplete. qPCR was used to profile the expression of 34 ß-defensin genes, representing each of the four clusters, in the ram reproductive tract. Distinct site-specific and differential expression profiles were detected across the reproductive tract of mature rams with preferential ß-defensin gene expression in the epididymis, recapitulating observations for orthologous genes in other species. CONCLUSIONS: This is the first comprehensive analysis of ß-defensin genes encoded by the ovine reference sequence, and the first report of an expanded repertoire of ß-defensin genes in this species. The preferential expression of these genes in the epididymis suggests a role in fertility, possibly providing immunoprotection for sperm within the female reproductive tract.

A Phase 1 study of ARQ 087, an oral pan-FGFR inhibitor in patients with advanced solid tumours.

BACKGROUND: ARQ 087 is an orally administered pan-FGFR inhibitor with multi-kinase activity. This Phase 1 study evaluated safety, pharmacokinetics, and pharmacodynamics of ARQ 087 and defined the recommended Phase 2 dose (RP2D). METHODS: Patients with advanced solid tumours received ARQ 087 administered initially at 25 mg every other day and dose-escalated from 25 to 425 mg daily (QD) continuous dosing. FGF19, 21, 23, and serum phosphate were assessed as potential biomarkers of target engagement. RESULTS: 80 patients were enrolled, 61 in dose-escalation/food-effect cohorts and 19 with pre-defined tumour types in the expansion cohort. The most common ARQ 087-related adverse events were fatigue (49%), nausea (46%), aspartate aminotransferase (AST) increase (30%), and diarrhoea (23%). Four patients (5%) experienced grade 1 treatment-related hyperphosphataemia. Dose-limiting toxicity was reversible grade 3 AST increase. The RP2D was 300 mg QD. Pharmacokinetics were linear and dose-proportional from 25 to 325 mg QD, and were unaffected by food. Statistically significant changes (P-value<0.05) suggest phosphate and FGF19 levels as markers of target engagement. In 18 evaluable patients with FGFR genetic alterations, 3 confirmed partial responses (two intrahepatic cholangiocarcinomas (iCCA) with FGFR2 fusions and one urothelial cancer with FGFR2 and FGF19 amplification) and two durable stable disease at ⩾16 weeks with tumour reduction (FGFR2 fusion-positive iCCA and adrenocortical carcinoma with FGFR1 amplification) were observed. CONCLUSIONS: ARQ 087 had manageable toxicity at the RP2D of 300 mg QD, showed pharmacodynamics effects, and achieved objective responses, notably in patients with FGFR2 genetic alterations.

Patient, treatment and discharge factors associated with hospital readmission within 30days after surgery for vulvar cancer.

OBJECTIVES: The majority of hospital readmissions are unexpected and considered adverse events. The goal of this study was to examine the factors associated with unplanned readmission after surgery for vulvar cancer. METHODS: Patient demographic, treatment, and discharge factors were collected on 363 patients with squamous cell carcinoma in situ or invasive cancer who underwent vulvectomy at our institution between January 2001 and June 2014. Clinical variables were correlated using χ2 test and Student's t-test as appropriate for univariate analysis. Multivariate analysis was then performed. RESULTS: Of 363 eligible patients, 35.6% had in situ disease and 64.5% had invasive disease. Radical vulvectomy was performed in 39.1% and 23.4% underwent lymph node assessment. Seventeen patients (4.7%) were readmitted within 30days, with length of stay ranging 2 to 37days and 35% of these patients required a re-operation. On univariate analyses comorbidities, radical vulvectomy, nodal assessment, initial length of stay, and discharge to a post acute care facility (PACF) were associated with hospital readmission. On multivariate analysis, only discharge to a PACF was significantly associated with readmission (OR 6.30, CI 1.12-35.53, P=0.04). Of those who were readmitted within 30days, 29.4% had been at a PACF whereas only 6.6% of the no readmission group had been discharged to PACF (P=0.003). CONCLUSIONS: Readmission affected 4.7% of our population, and was associated with lengthy hospitalization and reoperation. After controlling for patient comorbidities and surgical radicality, multivariate analysis suggested that discharge to a PACF was significantly associated with risk of readmission.

Pharmacokinetic parameters for single- and multi-dose regimens for subcutaneous administration of a high-dose ceftiofur crystalline-free acid to neonatal foals.

The objective of this study was to determine the pharmacokinetics of single- and multi-dose ceftiofur crystalline-free acid (CCFA) administered subcutaneously at a dose of 13.2 mg/kg to 12 neonatal foals 1-3 days of age. Six foals received a single subcutaneous dose, while 6 additional foals received 4 doses of CCFA at 48-h intervals. Blood samples were collected at pre-determined times following drug administration, and plasma concentrations of ceftiofur free acid equivalents (CFAE) were measured using high-performance liquid chromatography. Following single-dose administration of CCFA, the mean ± standard deviation maximum observed plasma concentration was 3.1 ± 0.6 µg/mL and observed time to maximal plasma concentration was 14.0 ± 4.9 h. Following multi-dose administration of CCFA, the mean ±standard deviation times above CFAE concentrations of ≥0.5 µg/mL and ≥2.0 µg/mL were 192.95 ± 15.86 h and 78.80 ± 15.31 h, respectively. The mean ± standard deviation area under the concentration vs time curve (AUC0→∝ ) was 246.2 ± 30.7 h × µg/mL and 172.7 ± 27.14 h × µg/mL following single- and multi-dose CCFA administrations, respectively. Subcutaneous administration of CCFA at 13.2 mg/kg in neonatal foals was clinically well- tolerated and resulted in plasma concentrations sufficient for the treatment of most bacterial pathogens associated with neonatal foal septicemia. Multi-dose administration of four doses at dosing interval of 48 h between treatments maintains appropriate therapeutic concentrations in neonatal foals.

The effect of chemotherapy on health-related quality of life in mesothelioma: results from the SWAMP trial.

BACKGROUND: The effect of chemotherapy on health-related quality of life (HRQoL) in malignant pleural mesothelioma (MPM) is poorly understood. Patient-individualised prognostication and prediction of treatment response from chemotherapy is useful but little evidence exists to guide practice. METHOD: Consecutive patients with MPM who were fit for first-line chemotherapy with pemetrexed and cisplatin\carboplatin were recruited and followed up for a minimum of 12 months. This study focussed on the HRQoL outcomes of these patients using the EQ-5D, EORTC QLQ-C30 and LC13. RESULTS: Seventy-three patients were recruited of which 58 received chemotherapy and 15 opted for best supportive care (BSC). Compliance with HRQoL questionnaires was 98% at baseline. The chemotherapy group maintained HRQoL compared with the BSC group whose overall HRQoL fell (P=0.006) with worsening dyspnoea and pain. The impact of chemotherapy was irrespective of histological subtype although those with non-epithelioid disease had worse HRQoL at later time points (P=0.012). Additionally, those with a falling mesothelin or improvement on modified-RECIST CT at early follow-up had a better HRQoL at 16 weeks. CONCLUSIONS: HRQoL was maintained following chemotherapy compared with a self-selected BSC group. Once chemotherapy is initiated, a falling mesothelin or improved RECIST CT findings infer a quality-of-life advantage.

The South West Area Mesothelioma and Pemetrexed trial: a multicentre prospective observational study evaluating novel markers of chemotherapy response and prognostication.

BACKGROUND: Robust markers that predict prognosis and detect early treatment response in malignant pleural mesothelioma (MPM) would enhance patient care. METHODS: Consecutive patients with MPM who were considered fit for first-line chemotherapy were prospectively recruited. Patients of similar performance status opting for best supportive care were included as a comparator group. Baseline and interval CT, PET-CT and serum markers (mesothelin, fibulin-3 and neutrophil-lymphocyte ratio (NLR)) were obtained, and patients followed up for a minimum 12 months. FINDINGS: Seventy-three patients were recruited (58 chemotherapy/15 comparator arm). Baseline TGV (total glycolytic volume on PET-CT) was an independent predictor of worse overall survival (OS) (P=0.001). Change in interval TGV(baseline/after two cycles of chemotherapy) did not predict OS or chemotherapy response on CT. Baseline NLR<4 was an independent predictor of better OS (median survival 453 (IQR 272-576) days vs NLR⩾4, 257 (IQR 147-490), P=0.002). Although baseline serum mesothelin did not predict OS, a falling level at 8 weeks significantly predicted longer time to progression (TTP) (P<0.001). INTERPRETATION: Neutrophil-lymphocyte ratio and baseline TGV predict prognosis in malignant pleural mesothelioma (MPM), but PET-CT is unhelpful in monitoring chemotherapy response. Serum mesothelin is a useful early treatment response marker when measured serially during chemotherapy and may have a role in evaluating patients' treatment response.

Changes in shear wave speed pre- and post-induction of labor: a feasibility study.

OBJECTIVE: To explore the feasibility of using shear wave speed (SWS) estimates to detect differences in cervical softening pre- and post-ripening in women undergoing induction of labor. METHODS: Subjects at 37-41 weeks' gestation undergoing cervical ripening before induction of labor were recruited (n = 20). Examinations, performed prior to administration of misoprostol and 4 h later included Bishop score, transvaginal ultrasound measurement of cervical length, and 10 replicate SWS measurements using an ultrasound system equipped with a prototype transducer (128 element, 3 mm diameter, 14 mm aperture) attached to the clinician's hand. Subjects were divided into two groups, 'not-in-labor' and 'marked-progression', based on cervical evaluation at the second examination. Measurements were compared via individual paired hypotheses tests and using a linear mixed model, with the latter also used to compare groups. Spearman's rank correlation coefficient was used to compare SWS with Bishop score. The linear mixed model can take into account clustered data and accommodate multiple predictors simultaneously. RESULTS: The Wilcoxon signed-rank paired test established a significant difference in pre- and post-ripening SWS, with mean SWS estimates of 2.53 ± 0.75 and 1.54 ± 0.31 m/s, respectively (P < 0.001) in the not-in-labor group (decrease in stiffness) and 1.58 ± 0.33 and 2.35 ± 0.65 m/s for the marked-progression group (increase in stiffness). The linear mixed model corroborated significant differences in pre- and post-ripening measurements in individual subjects (P < 0.001) as well as between groups (P < 0.0001). SWS estimates were significantly correlated with digitally-assessed cervical softness and marginally correlated with Bishop score as assessed by Spearman's rank correlation coefficient. CONCLUSIONS: In-vivo SWS estimates detected stiffness differences before and after misoprostol-induced softening in term pregnancies. This ultrasonic shear elasticity imaging technique shows promise for assessing cervical softness.

Reconstruction of the history of anthropogenic CO(2) concentrations in the ocean.

The release of fossil fuel CO(2) to the atmosphere by human activity has been implicated as the predominant cause of recent global climate change. The ocean plays a crucial role in mitigating the effects of this perturbation to the climate system, sequestering 20 to 35 per cent of anthropogenic CO(2) emissions. Although much progress has been made in recent years in understanding and quantifying this sink, considerable uncertainties remain as to the distribution of anthropogenic CO(2) in the ocean, its rate of uptake over the industrial era, and the relative roles of the ocean and terrestrial biosphere in anthropogenic CO(2) sequestration. Here we address these questions by presenting an observationally based reconstruction of the spatially resolved, time-dependent history of anthropogenic carbon in the ocean over the industrial era. Our approach is based on the recognition that the transport of tracers in the ocean can be described by a Green's function, which we estimate from tracer data using a maximum entropy deconvolution technique. Our results indicate that ocean uptake of anthropogenic CO(2) has increased sharply since the 1950s, with a small decline in the rate of increase in the last few decades. We estimate the inventory and uptake rate of anthropogenic CO(2) in 2008 at 140 +/- 25 Pg C and 2.3 +/- 0.6 Pg C yr(-1), respectively. We find that the Southern Ocean is the primary conduit by which this CO(2) enters the ocean (contributing over 40 per cent of the anthropogenic CO(2) inventory in the ocean in 2008). Our results also suggest that the terrestrial biosphere was a source of CO(2) until the 1940s, subsequently turning into a sink. Taken over the entire industrial period, and accounting for uncertainties, we estimate that the terrestrial biosphere has been anywhere from neutral to a net source of CO(2), contributing up to half as much CO(2) as has been taken up by the ocean over the same period.

Imaging protocol for suspected ureteric calculi in patients presenting to the emergency department.

AIM: To ensure diagnostic yields were adequate in patients with suspected ureteric calculi with and without haematuria, and to assess whether there was a significant difference between these two groups in men and women. MATERIALS AND METHODS: A retrospective analysis was undertaken of 513 patient records who attended the Emergency Department with suspected ureteric colic over 8 months. RESULTS: 513 patient records were evaluated. The overall positive rate for calculi was 45.4%, with an alternative diagnosis in 14.4%. Of the patients scanned with haematuria 49.36% were positive. The positive scan rate in males was significantly higher than in females (56% v. 31%, p < 0.0001). 32.79% of patients scanned without haematuria had a proven calculus. The positive rate in males without haematuria was 40.39% versus 27.14% in females. CONCLUSION: The overall diagnostic yield of 45.4% is acceptable according to national guidelines. A large number of patients scanned without haematuria were found to have a calculus. This review suggests that in males a negative urine dipstick should not preclude CT investigation for renal colic in the presence of a "classical" history. However, the number of female patients with negative scans suggests that further randomized studies are needed to identify the ideal investigation pathway in women.

Effects of two different knee tape procedures on lower-limb kinematics and kinetics in recreational runners.

The purpose of this study was to compare the effects of Mulligan's tape (MT) and kinesio tape (KT) with no tape (NT) on hip and knee kinematics and kinetics during running. Twenty-nine female recreational runners performed a series of 'run-throughs' along a 10-m runway under the three taping conditions. Two force plates and a 14-camera Vicon motion analysis system (Oxford Metrics, Inc., Oxford, UK) captured kinematic and kinetic data for each dependent variable from ground contact to toe off. Comparisons of each dependent variable under three taping conditions were assessed through Statistical Package for the Social Sciences (SPSS; SPSS, Inc., Chicago, Illinois, USA; P-value < 0.01) using repeated measure analyses of variance. For each dependent variable with a P-value < 0.01, repeated measures with pairwise comparisons and Bonferroni adjustment were conducted to compare the three taping conditions. MT induced a significant reduction in anterior and posterior hip forces, knee flexion angular velocity, knee extensor moments, and hip flexion and extension moments compared with NT and KT (P = 0.001). There was no difference in hip or knee, kinematics or kinetics, between KT and NT (P = 1.000). MT appears to influence hip and knee biomechanics during running in an asymptomatic sample, whereas KT appeared to be biomechanically not different from NT.

Estimation of shear wave speed in the human uterine cervix.

OBJECTIVES: To explore spatial variability within the cervix and the sensitivity of shear wave speed (SWS) to assess softness/stiffness differences in ripened (softened) vs unripened tissue. METHODS: We obtained SWS estimates from hysterectomy specimens (n = 22), a subset of which were ripened (n = 13). Multiple measurements were made longitudinally along the cervical canal on both the anterior and posterior sides of the cervix. Statistical tests of differences in the proximal vs distal, anterior vs posterior and ripened vs unripened cervix were performed with individual two-sample t-tests and a linear mixed model. RESULTS: Estimates of SWS increase monotonically from distal to proximal longitudinally along the cervix, they vary in the anterior compared to the posterior cervix and they are significantly different in ripened vs unripened cervical tissue. Specifically, the mid position SWS estimates for the unripened group were 3.45 ± 0.95 m/s (anterior; mean ± SD) and 3.56 ± 0.92 m/s (posterior), and 2.11 ± 0.45 m/s (anterior) and 2.68 ± 0.57 m/s (posterior) for the ripened group (P < 0.001). CONCLUSIONS: We propose that SWS estimation may be a valuable research and, ultimately, diagnostic tool for objective quantification of cervical stiffness/softness.

Tumor-infiltrating CD14-positive myeloid cells and CD8-positive T-cells prolong survival in patients with cervical carcinoma.

One of the hallmarks of cancer is the influx of myeloid cells. In our study, we investigated the constitution of tumor-infiltrating myeloid cells and their relationship to other tumor-infiltrating immune cells, tumor characteristics and the disease-specific survival of patients with cervical cancer (CxCa). Triple-color immunofluorescence confocal microscopy was used to locate, identify and quantify macrophages (CD14), their maturation status (CD33) and their polarization (CD163) in a cohort of 86 patients with cervical carcinoma. Quantification of the numbers of myeloid cells revealed that a strong intraepithelial infiltration of CD14+ cells, and more specifically the population of CD14+CD33-CD163- matured M1 macrophages, is associated with a large influx of intraepithelial T lymphocytes (p = 0.008), improved disease-specific survival (p = 0.007) and forms an independent prognostic factor for survival (p = 0.033). The intraepithelial CD8+ T-cell and regulatory T-cell (Treg) ratio also forms an independent prognostic factor (p = 0.010) and combination of these two factors reveals a further increased benefit in survival for patients whose tumor displays a dense infiltration with intraepithelial matured M1 macrophages and a high CD8 T-cell/Treg ratio, indicating that both populations of immune cells simultaneously improve survival. Subsequently, we made a heatmap including all known immune parameters for these patients, whereby we were able to identify different immune signatures in CxCa. These results indicate that reinforcement and activation of the intratumoral M1 macrophages may form an attractive immunotherapeutic option in CxCa.

Getting the balance right: qualitative evaluation of a holistic weight management intervention to address childhood obesity.

BACKGROUND: Childhood obesity is linked to a range of health and social problems. Solutions include the delivery of appropriate weight management interventions for those aged 16 and under. The 'Balance It! Getting the Balance Right' programme appears to be effective for those who complete the intervention, but the non-completion rate remains high. A qualitative evaluation was undertaken to explore the views of key stakeholders in the programme and identify possible reasons for non-completion. METHODS: Semi-structured interviews were conducted with a purposive sample of 16 NHS and local authority staff, and with 20 children (aged 4-16 years) and their families. A mosaic methodology was used, involving visual and verbal techniques employed to enable children of all ages to take an active role in expressing their opinions. RESULTS: Key themes included the challenges of approaching overweight children; positive outcomes for some families; and issues relating to communication and coordination. Participants spoke positively about the multi-disciplinary approach of 'Balance It!', but felt it could better meet the needs of its target population. CONCLUSIONS: Structured interventions help to ensure consistency and coherence in terms of approaches to childhood overweight and obesity. Whole family approaches may be most effective in enhancing the user experience.

Identification and typing of Francisella tularensis with a highly automated genotyping assay.

A PCR assay was developed to genotypically characterize Francisella tularensis and F. novicida. An integrated and partially redundant set of markers was selected to provide positive identification of these species, identify subspecies of F. tularensis and genotype 14 variable number tandem repeat (VNTR) markers. Assay performance was evaluated with 117 Francisella samples. Sample DNA was amplified, and the masses of the PCR products were determined with electrospray ionization/time of flight mass spectrometry (ESI-MS). The base compositions of the PCR amplicons were derived from these high-accuracy mass measurements and contrasted with databased information associated with each of the 25 assay markers. Species and subspecies determinations for all samples were fully concordant with results from established typing methods, and VNTR markers provided additional discrimination among samples. Sequence variants were observed with a number of assay markers, but these did not interfere with sample characterization, and served to increase the genetic diversity detected by the assay.