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Although surgical techniques for rhinoplasty and nasal reconstruction are well established, prospective research on postoperative morbidity remains limited. The aim of this pilot study was to assess costal and auricular cartilage donor site pain and morbidity in patients undergoing rhinoplasty and nasal reconstruction. In this prospective cohort study, we enrolled 55 patients undergoing nasal surgery that required costal or auricular cartilage harvest from February 2015 through May 2016. Each patient was given a symptom-specific patient survey that assessed general pain, nasal pain, graft donor site pain, graft donor site itching, color variation, skin stiffness and thickness, and graft donor site appearance at 1, 4, and 12 weeks after surgery. Our patient group was 55% female ( n = 30); the mean age was 47 years. Rib cartilage graft patients had significantly greater nasal pain than cartilage donor site pain. There was no significant difference in rib versus ear cartilage donor site pain. Nearly all patients reported that they were not at all concerned about their scar appearance or ear shape and appearance. No prior studies compare cartilage donor site morbidity in patients undergoing nasal surgery. Our findings challenge the conventional wisdom that utilizing auricular and costal cartilage results in high levels of donor site pain. Surgeons should have a low threshold to harvest rib or ear cartilage when it can improve surgical outcome.

The benefit of adding docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy to chemoradiotherapy (CRT) in head and neck squamous cell carcinoma (HNSCC) remains uncertain. We aimed to investigate whether ICT is well tolerated when given with prophylactic treatment against predicted adverse effects and which patients benefit most. A single-centre audit identified 132 HNSCC patients with stage IVa/b neck node-positive disease, prescribed TPF followed by CRT. TPF involved three cycles of docetaxel (75 mg/m2 IV) and cisplatin (75 mg/m2 IV) on day 1 plus 5-FU (750 mg/m2 IV) on days 2–5. Planned CRT was 66 Gy in 30 fractions of intensity-modulated radiotherapy with concurrent cisplatin (100 mg/m2 IV) at the beginning of week 1 and 4 (days 1 and 22). All patients received prophylactic antibiotics and granulocyte colony-stimulating factor. Median follow-up was 39.5 months. 92.4% of patients completed three cycles of TPF; 95.5% of patients started chemoradiotherapy. Grade 3/4 adverse events were low (febrile neutropenia 3.0%), with no toxicity-related deaths. 3-year overall survival was 67.2%; disease-specific survival was 78.7%; locoregional control was 78.3%. Distant metastases rate was 9.8% (3.0% in those without locoregional recurrence). Good performance status (p = 0.002) and poor tumour differentiation (p = 0.018) were associated with improved overall survival on multivariate analysis. With prophylactic antibiotics and granulocyte colony-stimulating factor TPF was well tolerated with good survival outcomes. TPF should remain a treatment option for stage IV neck node-positive patients with a good performance status. The use of tumour grade to aid patient selection for TPF warrants investigation.

Aims Treatment for head and neck cancers using definitive radiotherapy, with or without chemotherapy, is associated with significant acute toxicity. Our aim was to assess 90 day mortality after radical radiotherapy. A further aim was to identify patient, tumour or treatment factors associated with early death after treatment and whether these could be used to predict outcomes. Materials and methods In total, 1116 patients with squamous cell pharyngeal and larynx cancer between January 2011 and December 2015 were included. Patients with T1 larynx cancer were excluded. Patients were treated using radical radiotherapy, with or without chemotherapy. Ninety day mortality was calculated using survival of less than 135 days from the planned start date for radical radiotherapy, to include early deaths during and up to 90 days after treatment. Results Overall, 90 day mortality was 4.7%. Among the subgroup of patients treated with concurrent platinum chemotherapy, the 90 day mortality rate was 0.4%. Overall survival at 1, 3 and 5 years was 84%, 62% and 53%, respectively. Factors associated with a higher risk of early death included performance status > 1, haemoglobin 80 years and presence of multiple comorbidities. Conclusion We report excellent crude overall survival rates among our radically treated cohort of head and neck cancer patients. Several factors were associated with an increased risk of death within 90 days of completion of radical head and neck radiotherapy. Given the potential severe acute effects and the impact on patient quality of life associated with radical head and neck radiotherapy, this information is helpful to inform treatment-related discussions with patients.

Given the high prevalence of work-related musculoskeletal symptoms, increased appreciation for workplace ergonomics is critical. The purpose of this study is to assess work-related musculoskeletal symptoms and injury among otolaryngologists across subspecialties, as well as to quantify the understanding and application of ergonomic principles in the operating room.Cross-sectional study.An online REDCap survey was distributed electronically to University of Kansas faculty, alumni, and residents; members of the American Academy of Facial Plastic and Reconstructive Surgery; and residency program coordinators for distribution to residents and faculty between August 2016 and March 2017. The survey assessed caseload, ergonomic practices, and associated musculoskeletal symptoms by type of procedure and impact of symptoms on surgeon practice.The survey was distributed to 3,006 individuals. We received 377 responses (12.5%), with 63.9% reporting symptoms. The majority of respondents began to experience symptoms in residency or fellowship. Neck and shoulder were the most affected body areas across all types of surgeries. One-third of surgeons were formally taught or actively sought information on ergonomics principles. Among those who applied ergonomics in practice, 69.6% observed improvement in their symptoms.Although musculoskeletal issues are prevalent among otolaryngologists, awareness of surgical ergonomics principles among otolaryngologists remains limited. Early instruction in ergonomic principles is important because work-related musculoskeletal symptoms commonly present in residency. Most respondents reporting the application of ergonomic principles also acknowledge symptom improvement.NA. Laryngoscope, 128:632-640, 2018.

International audience; The Cherenkov Telescope Array (CTA) consortium aims to build the next-generation ground-based very-high-energy gamma-ray observatory. The array will feature different sizes of telescopes allowing it to cover a wide gamma-ray energy band from about 20 GeV to above 100 TeV. The highest energies, above 5 TeV, will be covered by a large number of Small-Sized Telescopes (SSTs) with a field-of-view of around 9°. The Gamma-ray Cherenkov Telescope (GCT), based on Schwarzschild–Couder dual-mirror optics, is one of the three proposed SST designs. The GCT is described in this contribution and the first images of Cherenkov showers obtained using the telescope and its camera are presented. These were obtained in November 2015 in Meudon, 2 http://www.cta-observatory.org France.

We investigated the potential of combining the hypoglycemic drug metformin (MET) and the antiepileptic drug valproic acid (VPA), which act via different biochemical pathways, to provide enhanced antitumor responses in prostate cancer. Prostate cancer cell lines (LNCaP and PC-3), normal prostate epithelial cells (PrEC), and patient-derived prostate tumor explants were treated with MET and/or VPA. Proliferation and apoptosis were assessed. The role of p53 in response to MET + VPA was assessed in cell lines using RNAi in LNCaP (p53+) and ectopic expression of p53 in PC-3 (p53−). The role of the androgen receptor (AR) was investigated using the AR antagonist enzalutamide. The combination of MET and VPA synergistically inhibited proliferation in LNCaP and PC-3, with no significant effect in PrEC. LNCaP, but not PC-3, demonstrated synergistic intrinsic apoptosis in response to MET + VPA. Knockdown of p53 in LNCaP (p53+, AR+) reduced the synergistic apoptotic response as did inhibition of AR. Ectopic expression of p53 in PC-3 (p53−, AR−) increased apoptosis in response to MET + VPA. In patient-derived prostate tumor explants, MET + VPA also induced a significant decrease in proliferation and an increase in apoptosis in tumor cells. In conclusion, we demonstrate that MET + VPA can synergistically kill more prostate cancer cells than either drug alone. The response is dependent on the presence of p53 and AR signaling, which have critical roles in prostate carcinogenesis. Further in vivo/ex vivo preclinical studies are required to determine the relative efficacy of MET + VPA as a potential treatment for prostate cancer. Mol Cancer Ther; 16(12); 2689–700. ©2017 AACR.

Objectives: To analyze the area under the curve (AUC) from 24-hour pharyngeal pH probes and evaluate this parameter as a predictor of disease severity for laryngopharyngeal reflux. Methods: Eighty patients met inclusion criteria of a completed 24-hour pharyngeal pH probe and Reflux Symptom Index (RSI) questionnaire. The AUC was calculated below a pH threshold of 5.5 using the trapezoidal rule. The RSI and RYAN scores were correlated with AUC values, and nonparametric tests were used for comparisons. Results: The median AUC value was 18 007 pH-seconds with an interquartile range (IQR) of 63 156, the median RSI score was 21 (IQR = 16), and the median RYAN score was 15.3 (IQR = 78). There was a Spearman’s correlation of .36 between the RSI scores and AUC values ( P = .001) and a moderate correlation between AUC values and RYAN scores (0.58, P < .001). An insignificant correlation of .19 between RYAN scores and RSI scores was observed ( P = .09). Conclusions: The AUC may be a useful objective value in establishing the diagnosis of laryngopharyngeal reflux. Prospective studies with larger patient populations are necessary to validate these findings and determine standardized thresholds for symptomatic patients.

Radiotherapy is widely used in cancer treatment, however the benefits can be limited by radiation-induced damage to neighboring normal tissues. Parthenolide (PTL) exhibits anti-inflammatory and anti-tumor properties and selectively induces radiosensitivity in prostate cancer cell lines, while protecting primary prostate epithelial cell lines from radiation-induced damage. Low doses of radiation have also been shown to protect from subsequent high-dose-radiation-induced apoptosis as well as DNA damage. These properties of PTL and low-dose radiation could be used to improve radiotherapy by killing more tumor cells and less normal cells. Sixteen-week-old male Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) and C57BL/6J mice were treated with PTL (40 mg/kg), dimethylaminoparthenolide (DMAPT, a PTL analogue with increased bioavailability) (100 mg/kg), or vehicle control three times over one week prior to combinations of low (10 mGy) and high (6 Gy) doses of whole-body X-irradiation. Tissues were analyzed for apoptosis at a range of time points up to 72 h postirradiation. Both PTL and DMAPT protected normal tissues, but not prostate tumor tissues, from a significant proportion of high-dose-radiation-induced apoptosis. DMAPT provided superior protection compared to PTL in normal dorsolateral prostate (71.7% reduction, P = 0.026), spleen (48.2% reduction, P = 0.0001) and colorectal tissue (38.0% reduction, P = 0.0002), and doubled radiation-induced apoptosis in TRAMP prostate tumor tissue (101.3% increase, P = 0.039). Both drugs induced the greatest radiosensitivity in TRAMP prostate tissue in areas with higher grade prostatic intraepithelial neoplasia (PIN) lesions. A 10 mGy dose delivered 3 h prior to a 6 Gy dose induced a radioadaptive apoptosis response in normal C57Bl/6J prostate (28.4% reduction, P = 0.045) and normal TRAMP spleen (13.6% reduction, P = 0.047), however the low-dose-adaptive radioprotection did not significantly add to the PTL/DMAPT-induced protection in normal tissues, nor did it affect tumor kill. These results support the use of the more bioavailable DMAPT and low-dose radiation, alone or in combination as useful radioprotectors of normal tissues to alleviate radiotherapy-induced side-effects in patients. The enhanced radiosensitisation in prostate tissues displaying high-grade PIN suggests that DMAPT also holds promise for targeted therapy of advanced prostate cancer, which may go on to become metastatic. The redox mechanisms involved in the differential radioprotection observed here suggest that increased radiotherapy efficacy by DMAPT is more broadly applicable to a range of cancer types. Refereed/Peer-reviewed

Aberrant activity of cyclin-dependent kinase (CDK) 8 is implicated in various cancers. While CDK8-targeting anticancer drugs are highly sought-after, no CDK8 inhibitor has yet reached clinical trials. Herein a large library of drug-like molecules was computationally screened using-two complementary cascades to identify potential CDK8 inhibitors. Thirty-three hits were identified to inhibit CDK8 and seven of them were active against colorectal cancer cell lines. Finally, the primary target was confirmed using three promising hits. Refereed/Peer-reviewed

The Soft X-ray focusing Telescope (SXT), India’s first X-ray telescope based on the principle of grazing incidence, was launched aboard the AstroSat and made operational on October 26, 2015. X-rays in the energy band of 0.3–8.0 keV are focussed on to a cooled charge coupled device thus providing medium resolution X-ray spectroscopy of cosmic X-ray sources of various types. It is the most sensitive X-ray instrument aboard the AstroSat. In its first year of operation, SXT has been used to observe objects ranging from active stars, compact binaries, supernova remnants, active galactic nuclei and clusters of galaxies in order to study its performance and quantify its characteriztics. Here, we present an overview of its design, mechanical hardware, electronics, data modes, observational constraints, pipeline processing and its in-orbit performance based on preliminary results from its characterization during the performance verification phase.

This study describes the clinical course of adult patients with type 2 diabetes taking a sulfonylurea and presenting to the hospital with severe hypoglycemia.This was a retrospective chart review of all patients15 years of age with type 2 diabetes and taking a sulfonylurea who presented to the emergency services of Auckland City Hospital over a 6-year period with severe hypoglycemia.One hundred eighty-five patients met the inclusion criteria. Their mean ± SD age was 71 ± 11 years, and known duration of diabetes was 14.7 ± 10 years. Of the patients, 167 had micro- and/or macrovascular complications of diabetes, and one-third had had a previous admission with hypoglycemia. Only 61 patients (33%) had a glomerular filtration rate of60 mL/min. The length of stay was not correlated with admission creatinine level (highest tertile of creatinine, 71 ± 93 h; lowest tertile, 51 ± 79 h). Recurrent in-hospital hypoglycemia occurred in over one-third of patients, and 28 (15%) were re-admitted to the hospital within 28 days of discharge for various reasons, including further hypoglycemia in 13 patients. Two patients died during their admission.Patients with type 2 diabetes presenting to the hospital with sulfonylurea-associated hypoglycemia have a high burden of comorbidity, require a long hospital stay, and are at risk of subsequent re-admission to hospital. Careful evaluation of their best future treatment strategies must be undertaken taking account of their comorbidities, including their renal function.

Background There is a need to improve the systemic treatment of advanced adenoid cystic carcinoma (ACC). Response rates to chemotherapy are poor and preliminary investigations of molecularly targeted agents have been disappointing. In this study, we evaluate sorafenib, an oral multikinase inhibitor, which has an attractive targeting profile for this disease. Methods In a single-arm phase II trial, patients with unresectable locally recurrent and/or metastatic ACC were treated with sorafenib 400 mg bid. Results Twenty-three patients, median age 51 years, were recruited from 2009 to 2011. Median progression-free survival (PFS) and overall survival (OS) were 11.3 and 19.6 months, respectively. PFS at 6 and 12 months were 69.3% and 46.2%, respectively. Sorafenib was only reasonably well tolerated, and 13 patients (57%) experienced grade 3 toxicity. Conclusion Sorafenib showed modest activity in ACC with a 12-month PFS of 46.2%. Sorafenib 400 mg bid was associated with significant toxicity and, taken together with limited effectiveness, cannot be enthusiastically recommended for further evaluation. © 2014 Wiley Periodicals, Inc. Head Neck 37: 182-187, 2015

Phosphorylation of eIF4E by human mitogen-activated protein kinase (MAPK)-interacting kinases (Mnks) is crucial for human tumourigenesis and development. Targeting Mnks may provide a novel anticancer therapeutic strategy. However, the lack of selective Mnk inhibitors has so far hampered pharmacological target validation and clinical drug development. Herein, we report, for the first time, the discovery of a series of 5-(2-(phenylamino)pyrimidin-4-yl)thiazole-2(3H)-one derivatives as Mnk inhibitors. Several derivatives demonstrate very potent Mnk2 inhibitory activity. The most active and selective compounds were tested against a panel of cancer cell lines, and the results confirm the cell-type-specific effect of these Mnk inhibitors. Detailed cellular mechanistic studies reveal that Mnk inhibitors are capable of reducing the expression level of anti-apoptotic protein Mcl-1, and of promoting apoptosis in MV4-11 acute myeloid leukaemia cells. Refereed/Peer-reviewed

To determine the incidence of vocal cord (VC) paralysis and dysphagia after aortic arch reconstruction, including the Norwood procedure.Tertiary children's hospital.Retrospective cohort.Database/chart review of neonates requiring Norwood or arch surgery between January 2005 and December 2012. Demographics, postoperative VC function, dysphagia, need for gastrostomy tube and/or tracheotomy, and long-term follow-up were reviewed.One hundred fifty-one consecutive subjects (96 Norwood, 55 aortic arch) were reviewed. Median age at repair was 9 days (interquartile range [IQR], 7-13) for Norwood and 24 days (IQR, 12-49) for arch reconstruction (P.001). Documentation of VC motion abnormality was found in 60 of 104 (57.6%) subjects and unavailable in 47 (16 without documentation and 31 who died prior to extubation). There were no significant differences in proportions of documented VC motion (P = .337), dysphagia (P = .987), and VC paralysis (P = .706) between the arch and Norwood groups. Dysphagia was found in 73.5% of Norwood and 69.2% of arch subjects who had documented VC paralysis. Even without unilateral VC paralysis (UVCP), dysphagia was present (56% Norwood, 61% arch). Overall, 120 of 151 (79.5%) required feeding evaluation and a modified feeding regimen. Gastrostomy was required in 31% of Norwood and 23.6% of arch reconstruction overall. To date, mortality in this series is 55 of 151 (36.4%) patients. Of those with VC paralysis, only 23 (22%) had any otolaryngology follow-up after discharge from surgery. More than 75% with VC paralysis with follow-up after hospital discharge had persistent VC paralysis 11.5 months after diagnosis.There is high incidence of UVCP and dysphagia after Norwood and arch reconstruction. Dysphagia was highly prevalent in both groups even without UVCP. Preoperative discussion on vocal cord function and dysphagia should be considered.

It is suggested that replication projects may be valuable in teaching research methods, and also address the current need in psychology for more independent verification of published studies. Their use in an undergraduate methods course is described, involving student teams who performed direct replications of four well–known experiments, yielding results which were subsequently published online. Illustrative data are given for the one successful replication and three failures obtained, and practical suggestions are given for incorporating replication projects intoa methods course as an alternative to the usual term project. It is also noted that the published success rates of replication attempts appear to be higher for those studies that were performed as class projects.

An objective evidence-based review of the metrics used to evaluate applicants entering our field ultimately found these figures to have upward trends without any major correlation to performance in residency. The rise of these metrics coincides with a yearly drop in senior applicants, and in 2017, nearly 10% of programs did not match their contingent. The causes of unmatched spots must be examined to ensure that the field of otolaryngology can continue to grow and attract medical students who will excel in our field. Considerations into revising the applicant selection process, early introduction and mentorship within the otolaryngology field, and changes to the current otolaryngology interview process are discussed.

Importance Inefficiency in the operating room (OR) is detrimental to the patient, the hospital, and the surgeon. Head and neck procedures requiring microvascular reconstruction are complex, lengthy operations in which prolonged operative time is associated with higher complication rates and increased costs. Objective To use Lean methodology to identify potential OR efficiency improvement opportunities for head and neck surgical cases involving free tissue transfer, to implement an intervention, the free flap plan of the day, and to evaluate OR times after implementation. Design, Setting, and Participants Phase 1: In 2015, with the assistance of the Lean Promotion Office at our institution, a tertiary academic medical center, we identified efficiency-improvement opportunities for 10 patients undergoing free flap reconstruction. Phase 2: A single intervention, the free flap plan of the day, was implemented on February 1, 2016. A retrospective medical record review of head and neck free flap reconstructions beginning 2 years before the implementation of the intervention and ending 2 years after the intervention was performed from February 1, 2014 until February 1, 2018 to analyze OR times, cost, and complications. Mean OR times were compared using thettest. Main Outcomes and Measures In-room-to-incision time and total OR time. Results Phase 1: The surgical procedures of 10 patients undergoing free flap reconstruction were observed by Lean specialists, and a time study with a process map was completed. Using this framework, major opportunities for decreasing intraoperative time waste were identified. Multiple communication breakdowns were seen to drive intraoperative time waste; therefore, a free flap plan of the day was created to improve communication between team members. Phase 2: 200 patients were included in the study and were categorized into 2 groups, no plan group (n = 104) and plan group (n = 96), based on whether the plan of the day was used or not. The age and sex distributions of the study participants were not collected. Mean in-room-to-incision time was 54.3 minutes for the no plan group and 47.2 minutes for the plan group (difference, 7.1 minutes; 95% CI, 3.8-10.4 minutes). Mean total OR time was 524.1 minutes for the no plan group and 467.4 minutes for the plan group (difference, 56.7 minutes; 95% CI, 23.6-89.6 minutes). Conclusions and Relevance Lean methodology was used to identify efficiency-improvement opportunities for head and neck free flap reconstruction procedures and to design a focused intervention. A free flap plan of the day was used in this study to improve communication between the OR team and was found to improve efficiency and be associated with reduced OR times.

While radiotherapy is widely used in cancer treatment, the benefits can be limited by radiation-induced damage to neighboring healthy tissues. We previously demonstrated in mice that the anti-inflammatory compound dimethylaminoparthenolide (DMAPT) selectively induces radiosensitivity in prostate tumor tissue from transgenic adenocarcinoma of mouse prostate (TRAMP) mice, while simultaneously protecting healthy tissues from 6 Gy whole-body radiation-induced apoptosis. Here, we examined the radioprotective effect of DMAPT on fibrosis in normal tissues after a partial-body fractionated radiation protocol that more closely mimics the image-guided fractionated radiotherapy protocols used clinically. Male C57BL/6J mice, 16 weeks old, received 20 Gy fractionated doses of X rays (2 Gy daily fractions, five days/week for two weeks) or sham irradiation to the lower abdomen, with or without a prior 20 mGy dose to mimic an image dose. In addition, mice received thrice weekly DMAPT (100 mg/kg by oral gavage) or vehicle control from 15 weeks of age until time of analysis at 6 weeks postirradiation. In the absence of exposure to radiation, there were no significant differences observed in the tissues of DMAPT and vehicle-treated mice (P > 0.05). DMAPT treatment significantly reduced radiation-induced testis weight loss by 60.9% (P < 0.0001), protected against a decrease in the seminiferous tubule diameter by 42.1% (P < 0.0001) and largely preserved testis morphology. Inclusion of the image dose had no significant effect on testis mass, seminiferous tubule diameter or testis morphology. DMAPT reduced radiation-induced fibrosis in the corpus cavernous region of the penis (98.1% reduction, P = 0.009) and in the muscle layer around the bladder (80.1% reduction, P = 0.0001). There was also a trend towards reduced collagen infiltration into the submucosal and muscle layers in the rectum. These results suggest that DMAPT could be useful in providing protection from the radiation-induced side effects of impotence and infertility, urinary incontinence and fecal urgency resulting from prostate cancer radiotherapy. DMAPT is a very well-tolerated drug and can conveniently be delivered orally without strict time windows relative to radiation exposure. Protection of normal tissues by DMAPT could potentially be useful in radiotherapy of other cancer types as well.

A long-term study of annual survival, longevity, and site fidelity in the eastern coastal population of the Painted Bunting (Passerina ciris) during the breeding season was conducted from 1999 through 2018 in the outer coastal plain of the Atlantic coast of the United States. Painted Buntings were uniquely color-banded from 1999 through 2003 at 40 study sites paired at 20 locations from southeastern NC south to northeastern FL. Survival analysis used capture histories through 2005 for 994 birds banded as hatch-year and 2,420 birds banded as post-hatch-year (adults). Annual estimates of apparent survival (1999-2004) averaged 0.71 and 0.66 for adult males and females, respectively, and 0.33 for hatch-year birds. We did not find evidence that survival differed in relation to latitude or extent of human development near study sites, although estimates for adult females were higher for birds banded on sheltered islands compared to the mainland. Expected time in the population, based on estimated survival, was 3.9 and 3.4 years for adult males and females, respectively. The oldest observed birds were a 14-year-old male observed in June 2016 at Harris Neck National Wildlife Refuge, GA, the site at which he had been banded in July 2003 as a second-year bird, and a 13-year-old male seen at Ft. George Island, FL, in June 2016, 2 km across a tidal estuary from the site where the bird was banded in August 2003 as hatch-year. The males were sighted at these 2 sites in 9 and 11 different years, respectively. Overall, 78% (males) and 81% (females) of resightings and recaptures of birds banded as adults occurred at the same study site where individuals were banded, compared to 59% (males) and 60% (females) of birds banded as hatch-year. Known mortalities of banded buntings included 9 birds trapped for the caged-bird trade. This study shows the potential for high survival and longevity in the eastern coastal population of the Painted Bunting, and given evidence of high site fidelity in the breeding range, the vulnerability of the population to human development along the southeastern US coast as well as to illegal trapping.

Objectives/Hypothesis Chronic rhinosinusitis(CRS) results in significant morbidity and health care expenditure. Safety and efficacy of nasal irrigation use in the treatment of pediatric CRS have been demonstrated, but long-term outcomes are unknown. We reviewed characteristics and treatment outcomes after 6 weeks of once daily nasal irrigation in pediatric CRS based on computed tomography (CT) scans, and summarized parental reports of subsequent use of nasal irrigation for recurring symptoms Study Design Retrospective cohort study and cross-sectional survey. Methods Review and survey of 144 pediatric CRS patients diagnosed between July 2003 and January 2012. Results One hundred four patients were reviewed. Mean age was 8.0 years, and 65.4% were male. Presenting symptoms included congestion (95.2%), cough (79.8%), rhinorrhea (60.6%), headache (48.1%), and fatigue (40.4%). Comorbidities included positive allergy test (50%), asthma (57.3%), and gastroesophageal reflux disease (28.2%). After 6 weeks, 57.7% of patients reported complete resolution of symptoms. Reductions in Lund–Mackay CT scores were 4.14 and 4.38 on the left and right sides, respectively (P

Cancer of the prostate is a highly prevalent disease with a heterogeneous aetiology and prognosis. Current understanding of the biological mechanisms underlying the responses of prostate tissue to ionizing radiation exposure, including cancer induction, is surprisingly limited for both high- and low-dose exposures. As population exposure to radiation increases, largely through medical imaging, a better understanding of the response of the prostate to radiation exposure is required. Low-dose radiation-induced adaptive responses for increased cancer latency and decreased cancer frequency have been demonstrated in mouse models, largely for hematological cancers. This study examines the effects of high- and low-dose whole-body radiation exposure on prostate cancer development using an autochthonous mouse model of prostate cancer: TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP). TRAMP mice were exposed to single acute high (2 Gy), low (50 mGy) and repeated low (5 × 50 mGy) doses of X rays to evaluate both the potential prostate cancer promoting effects of high-dose radiation and low-dose adaptive response phenomena in this prostate cancer model. Prostate weights and histopathology were examined to evaluate gross changes in cancer development and, in mice exposed to a single 2 Gy dose, time to palpable tumor was examined. Proliferation (Ki-67), apoptosis, DNA damage (γ-H2AX) and transgene expression (large T-antigen) were examined within TRAMP prostate sections. Neither high- nor low-dose radiation-induced effects on prostate cancer progression were observed for any of the endpoints studied. Lack of observable effects of high- or low-dose radiation exposure suggests that modulation of tumorigenesis in the TRAMP model is largely resistant to such exposures. However, further study is required to better assess the effects of radiation exposure using alternative prostate cancer models that incorporate normal prostate and in those that are not driven by SV40 large T antigen.

The TRAMP (Transgenic Adenocarcinoma of the Mouse Prostate) and LADY (Probasin-large T antigen transgenic mouse) mice are widely used autochthonous models of prostate cancer. Both models utilise probasin promoters to direct androgen-regulated expression of oncogenic SV40 specifically to epithelial cells of the mouse prostate. The oncogenic processes and phenotypes which result mimic many features of human prostate cancer, making these transgenic mouse models useful experimental systems. The terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP in situ nick end labelling (TUNEL) assay is a commonly used method for the detection of cells undergoing apoptosis. In this study, we demonstrate false-positive TUNEL staining in frozen prostate tissue from TRAMP and LADY mice, which was not observed in non-transgenic control animals and is not due to non-specific binding of labelled-dUTP substrate. The false-positive signal co-localised with large SV40 T-antigen expression. False-positive signal was apparent using multiple commercial TUNEL kits with different detection systems. These results caution against the use of the TUNEL assay for detection of apoptosis in frozen prostate tissue of large T-antigen based autochthonous transgenic models of prostate cancer.

Objectives: We performed a retrospective study of cases from 2005 to 2010 at an academic tertiary care center to analyze the factors that influence morbidity in surgical management of thyroid malignancy. Methods: The rates of recurrent laryngeal nerve (RLN) injury and hypoparathyroidism (HPT) were analyzed in the entire cohort. The comparison groups were 1) primary surgery versus revision; 2) total thyroidectomy versus total thyroidectomy combined with neck node dissection; and 3) two groups defined by surgical technique according to the RLN approach: Group 1, in which the RLN was identified inferiorly in the tracheoesophageal groove, and group 2, in which the RLN was identified near the cricothyroid joint point of entry. Results: We reviewed 308 patients who underwent surgery for thyroid cancer. Thirty-six (11.7%) had temporary HPT, and 8 (2.6%) had permanent HPT. Of a total of 586 RLNs at risk, 16 (2.7%) had temporary damage and 2 (0.3%) had permanent damage. The incidences of temporary RLN injury significantly differed between the primary-surgery and revision-surgery groups (2.5% versus 15.6%; p = 0.001), and also between the groups with total thyroidectomy and thyroidectomy with neck dissection (1.2% versus 7.8%; p = 0.027). The incidences of temporary HPT were significantly different between the groups with primary surgery and revision surgery (6.6% versus 31.3%; p = 0.001), between the groups with total thyroidectomy and total thyroidectomy with neck dissection (4.7% versus 15.6%; p = 0.009), and between group 1 and group 2 (surgical technique in terms of RLN approach; 8.2% versus 17.9%; p = 0.011). Permanent HPT and permanent RLN injury both occurred rarely in this cohort, with no significant differences among comparison groups. Conclusions: Our study shows a higher incidence of temporary RLN injury and temporary HPT in revision surgery cases and in total thyroidectomy with neck dissection. Temporary HPT was significantly more common when the RLN was identified near the cricothyroid joint.

Background Acute cervical lymphadenitis is a common condition often times requiring antibiotic therapy and possible surgical drainage. The objective of this study was to describe the clinical characteristics, diagnostic and therapeutic management of children requiring surgical drainage for acute cervical lymphadenitis. Methods A retrospective, descriptive study was performed at a Midwestern US tertiary-care children's hospital on all immunocompetent children who underwent an incision and drainage procedure of cervical lymphadenitis from January 1999 to July 2009. Results A total of 277 patients were identified. Males represented 51% and the median age was 28 months (IQR: 13–59). Lymphadenitis was unilateral in 243 (87.7%) cases and bilateral in 19 (6.9%). Median length of hospital stay was 4 days (IQR: 3–5). Aerobic, anaerobic, acid fast bacillus (AFB), and fungal cultures were obtained intraoperatively in 99%, 98%, 82%, and 78% of cases, respectively. However no fungal cultures were positive and only 1% of anaerobic and 2% of AFB cultures were positive. The most common bacterial etiology was Staphylococcus aureus (35.7%) and Streptococcus pyogenes (18.8%). Of all cultures, 32% were negative. Overall, 22% were positive for methicillin susceptible S. aureus (MSSA) and 13.7% for methicillin resistant S. aureus (MRSA), with 96% MSSA and 100% MRSA susceptible to clindamycin. Median duration of discharge antibiotics prescribed was 10 days (IQR: 7–11). Only 12 (4.5%) patients required a repeat incision and drainage within 3 months. Conclusions A single antibiotic that treats S. pyogenes and S. aureus should be the empiric antibiotic for cervical lymphadenitis requiring incision and drain. We recommend sending only aerobic cultures intraoperatively as a routine practice as other pathogens are rare.

Aims Nasopharyngeal cancer (NPC) is relatively uncommon, especially in the Western world. We report our single institution experience of 20 years of data in 128 patients with NPC, including responses to different treatment modalities and outcomes by histological subtype. Materials and methods NPC patients presenting from 1992 to 2005 were located on the cancer registry database. Demographic data included age, gender, length of presenting symptoms and stage. World Health Organization classification (2005) was used for histological subtyping. The date of recurrence and survival outcomes were analysed using Kaplan–Meier curves. Results Presentation data were analysed from 128 patients; the survival analysis included 123 patients. The median age at presentation was 57.7 years. Stage III and IV presentation rates were 34 and 38%, respectively. The most common presenting symptom was a palpable neck lump (55%) and the median duration of symptoms was 16 weeks. Forty-eight patients received radiotherapy alone and 75 received chemoradiotherapy. The median overall survival in chemoradiotherapy patients was 80.3 months versus 28.5 months with radiotherapy alone ( P = 0.003). A significant difference was also seen with recurrence-free survival (RFS) ( P = 0.017). Type 1 keratinising carcinoma had a significantly worse overall survival ( P = 0.04) and a similar but non-statistically significant trend was seen for RFS ( P = 0.051). The multivariate analysis for overall survival showed that histological subtype (hazard ratio 2.7, 95% confidence interval 1.3–5.5, P = 0.034), age (hazard ratio 2.3, 95% confidence interval 1.1–4.9, P = 0.018) and N stage (hazard ratio 3.7, 95% confidence interval 1.4–9.4, P = 0.024) were prognostic factors. Conclusions We present the first large-scale, single-centre retrospective review of NPC in a UK-based population. Demographic data were similar to that in other Western populations, with a significantly worse survival outcome in the keratinising group. Further prospective study of outcome in Western populations accounting for newer radiotherapy techniques such as intensity-modulated radiotherapy and dose escalation, particularly in the keratinising population who were more likely to present with an isolated local recurrence, is recommended.

The D/H isotope ratio is used to attribute boundary layer humidity changes to the set of contributing fluxes for a case following a snowstorm in which a snow pack of about 10 cm vanished. Profiles of H2O and CO2 mixing ratio, D/H isotope ratio, and several thermodynamic properties were measured from the surface to 300 m every 15 min during four winter days near Boulder, Colorado. Coeval analysis of the D/H ratios and CO2 concentrations find these two variables to be complementary with the former being sensitive to daytime surface fluxes and the latter particularly indicative of nocturnal surface sources. Together they capture evidence for strong vertical mixing during the day, weaker mixing by turbulent bursts and low level jets within the nocturnal stable boundary layer during the night, and frost formation in the morning. The profiles are generally not well described with a gradient mixing line analysis because D/H ratios of the end members (i.e., surface fluxes and the free troposphere) evolve throughout the day which leads to large uncertainties in the estimate of the D/H ratio of surface water flux. A mass balance model is constructed for the snow pack, and constrained with observations to provide an optimal estimate of the partitioning of the surface water flux into contributions from sublimation, evaporation of melt water in the snow and evaporation from ponds. Results show that while vapor measurements are important in constraining surface fluxes, measurements of the source reservoirs (soil water, snow pack and standing liquid) offer stronger constraint on the surface water balance. Measurements of surface water are therefore essential in developing observational programs that seek to use isotopic data for flux attribution.

Background Electrochemotherapy (ECT) is an effective local treatment for cutaneous metastasis. Treatment involves the administration of chemotherapeutic drugs followed by delivery of electrical pulses to the tumour. The aim of this study was to investigate the effectiveness of ECT in cutaneous metastases of melanoma and to identify factors which affect (beneficially or adversely) the outcome. Methods 13 cancer centres in the International Network for Sharing Practices on Electrochemotherapy (INSPECT) consecutively and prospectively uploaded data to a common database. ECT consisted of intratumoural or intravenous injection of bleomycin, followed by application of electric pulses under local or general anaesthesia. Results 151 patients with metastatic melanoma were identified from the database, 114 of which had follow-up data of 60 days or more. 80 of these patients (73%) experienced an overall response (complete response + partial response = OR). 394 lesions were treated, of which 306 (77%) revealed an OR, 229 a complete response (58%). In multivariate analysis, factors positively associated with overall response were coverage of deep margins, absence of visceral metastases, presence of lymphoedema, treatment of non-irradiated areas were factors significantly influencing treatment efficacy. Factors significant associated to a complete response to ECT treatment were: coverage of deep margins, previous irradiation of treated area, and tumour size (

International audience; The toxicity of tritium is a public health concern given its presence and mobility in the environment. For risk predictions using radiological protection models, it is essential to allocate an appropriate radiation weighting factor (WR). This in turn should be consistent with the observed relative biological effectiveness (RBE) of tritium beta radiation. Although the International Commission on Radiological Protection (ICRP) currently recommends a WR of 1 for the calculation of committed effective dose for X rays, gamma rays and electrons of all energies, including tritium energies, there are concerns that tritium health risks are underestimated and that current regulatory tritium drinking water standards need revision. In this study, we investigated potential cytotoxic and genotoxic effects in mouse spleen after one month and eight months of chronic exposure to low-dose tritiated water (HTO). The dose regimes studied were designed to mimic human chronic consumption of HTO at levels of 10 kBq/l, 1 MBq/l and 20 MBq/l. The total doses from these radiation exposures ranged from 0.01 to 180 mGy. We also compared the biological effects of exposure to HTO with equivalent exposure to external whole-body 60Co gamma rays. Changes in spleen weight and somatic intrachromosomal recombination (DNA inversions) in spleen tissue of pKZ1Tg/+ mice were monitored. Our results showed no overall changes in either spleen organ weights and no increase mouse splenic intrachromosomal recombination frequencies, indicating that current drinking water standards for tritium exposure in the form of HTO are likely to be adequately protective against cytotoxic and genotoxic damage in spleen. These results demonstrate no evidence for cytotoxicity or genotoxicity in mouse spleen following chronic exposures to HTO activities (or equivalent gamma doses) up to 20 MBq/L. © 2016 by Radiation Research Society.

A systematic review and meta-analyses were conducted to evaluate the effects of interventions to reduce sugar-sweetened beverages (SSB) or increase water intakes and to examine the impact of behaviour change techniques (BCTs) in consumption patterns. Randomized and nonrandomized controlled trials published after January 1990 and until December 2016 reporting daily changes in intakes of SSB or water in volumetric measurements (mL d

Reversible addition-fragmentation chain transfer (RAFT) copolymerization of styrene (St) and 4-(diphenylphosphino)styrene (DPPS) is explored to establish the statistical distribution of the phosphine-functional monomer within the copolymer. RAFT copolymerization of St and DPPS at a variety of feed ratios provides phosphine-functional copolymers of low dispersity at moderate monomer conversion (Ð 60%). In all cases, the fraction of DPPS in the resulting polymers is greater than that in the monomer feed. Estimation of copolymerization reactivity ratios indicates DPPS has a strong tendency to homopolymerize while St preferentially copolymerizes with DPPS (rDPPS = 4.4; rSt = 0.31). The utility of the copolymers as macro-RAFT agents in block copolymer synthesis is demonstrated via chain extension with hydrophilic acrylamide (N,N-dimethylacrylamide (DMAm)) and acrylate (poly(ethylene glycol) methyl ether acrylate (mPEGA), and di(ethylene glycol) ethyl ether acrylate (EDEGA)) monomers. Finally, access to polymers containing phosphine oxide and phosphonium salt functionalities is shown through postpolymerization modification of the phosphine-containing copolymers.

Objective The aim was to review a pathway of care for diabetic patients found to have retinal artery emboli detected by retinal screening. Design This was a retrospective review of a pathway agreed in 2001 by a multidisciplinary team. Materials and methods The prospectively collected Gloucestershire Diabetic Retinal Screening Programme database was reviewed; patients sent for carotid duplex imaging underwent review of their scan results and their casenotes. Results The prevalence of retinal emboli was 214 out of 25,299 diabetic patients who had retinal screening (0.85%). Some 200 diabetic patients underwent carotid duplex imaging; 23 had ipsilateral and 2 had contralateral carotid stenosis >70%. Of these, ten patients underwent carotid endarterectomy without any major morbidity. Conculsions A pathway was established for the small number of patients with retinal emboli, and could be tested in other populations.

The performance of the PAW instrumentation on the 60kg Beagle 2 lander for ESA’s 2003 Mars Express mission will be described. Beagle 2 will search for organic material on and below the surface of Mars in addition to a study of the inorganic chemistry and mineralogy of the landing site. The lander will utilize acquisition and preparation tools to obtain samples from below the surface, and both under and inside rocks. In situ analysis will include examination of samples with an optical microscope, Mossbauer and fluorescent X-ray spectrometers. Extracted samples will be returned to the lander for analysis, in particular a search for organics and a measurement of their isotopic composition. The PAW experiment performance data will be described along with the status of the project.

The Low Resolution Spectrometer of the MIRI, which forms part of the imager module, will provide R~100 long-slit and slitless spectroscopy from 5 to 12 micron. The design is optimised for observations of compact sources, such as exoplanet host stars. We provide here an overview of the design of the LRS, and its performance as measured during extensive test campaigns, examining in particular the delivered image quality, dispersion, and resolving power, as well as spectrophotometric performance, flatfield accuracy and the effects of fringing. We describe the operational concept of the slitless mode, which is optimally suited to transit spectroscopy of exoplanet atmospheres. The LRS mode of the MIRI was found to perform consistently with its requirements and goals., Comment: published in PASP, vol. 127, issue 953, pp.623-632, 2015

1. The metabolism of the anti-inflammatory diterpenoid polyandric acid A (PAA), a constituent of the Australian Aboriginal medicinal plant Dodonaea polyandra, and its de-esterified alcohol metabolite, hydrolysed polyandric acid A (PAAH) was studied in vitro using human liver microsomes (HLM) and recombinant UDP-glucuronosyltransferase (UGT) and cytochrome P450 (CYP) enzymes.2. Hydrolysis of PAA to yield PAAH occurred upon incubation with HLM. Further incubations of PAAH with HLM in the presence of UGT and CYP cofactors resulted in significant depletion, with UGT-mediated depletion as the major pathway.3. Reaction phenotyping utilising selective enzyme inhibitors and recombinant human UGT and CYP enzymes revealed UGT2B7 and UGT1A1, and CYP2C9 and CYP3A4 as the major enzymes involved in the metabolism of PAAH.4. Analysis of incubations of PAAH with UDP-glucuronic acid-supplemented HLM and recombinant enzymes by UPLC/MS/MS identified three glucuronide metabolites. The metabolites were further characterised by β-glucuronidase and mild alkaline hydrolysis. The acyl glucuronide of PAAH was shown to be the major metabolite.5. This study demonstrates the in vitro metabolism of PAA and PAAH and represents the first systematic study of the metabolism of an active constituent of an Australian Aboriginal medicinal plant. Refereed/Peer-reviewed

The Solar wind Magnetosphere Ionosphere Link Explorer (SMILE) is a collaborative science mission between ESA and the Chinese Academy of Sciences (CAS). SMILE is a novel self-standing mission to observe the coupling of the solar wind and Earth's magnetosphere via X-Ray imaging of the solar wind -- magnetosphere interaction zones, UV imaging of global auroral distributions and simultaneous in-situ solar wind, magnetosheath plasma and magnetic field measurements. The SMILE mission proposal was submitted by a consortium of European, Chinese and Canadian scientists following a joint call for mission by ESA and CAS. It was formally selected by ESA's Science Programme Committee (SPC) as an element of the ESA Science Program in November 2015, with the goal of a launch at the end of 2021. In order to achieve its scientific objectives, the SMILE payload will comprise four instruments: the Soft X-ray Imager (SXI), which will spectrally map the Earth's magnetopause, magnetosheath and magnetospheric cusps; the UltraViolet Imager (UVI), dedicated to imaging the auroral regions; the Light Ion Analyser (LIA) and the MAGnetometer (MAG), which will establish the solar wind properties simultaneously with the imaging instruments. We report on the status of the mission and payload developments and the findings of a design study carried out in parallel at the concurrent design facilities (CDF) of ESA and CAS in October/November 2015.

Monetary contingency contracts (MCCs), in which deposited money is returned contingent on weight loss, could promote weight/adiposity reduction. This study piloted individual- and pair-based MCCs (when refunds are contingent on two individuals losing weight) and assessed effects on weight/body composition.Seventy-seven participants with BMI greater than 25 kg/mSeventy-seven participants (P-PBR n = 16; P-IR n = 20; I-IR n = 22; comparison n = 19) were recruited. Deposit amount was significantly positively associated with reductions in weight/BMI. At 8 weeks, the P-PBR condition reduced fat mass more than all other conditions (P 0.05) and reduced weight/BMI more than the I-IR condition (P 0.05).The large effect of P-PBR on fat mass suggests it would be valuable to conduct a fully powered, randomized controlled trial of pair-based MCCs.

The in vivo mouse transgenic pKZ1 chromosomal inversion assay is a sensitive assay that responds to very low doses of DNA-damaging agents. pKZ1 inversions are measured as the frequency of cells expressing E. coli bgalactosidase protein, which can only be produced from an inverted pKZ1 transgene. In previous studies we reported that a single whole-body low dose of 0.01 mGy X rays alone caused an increase in pKZ1 chromosomal inversions in spleen when analyzed 3 days postirradiation, and yet this same dose could protect from high-dose-induced inversions when delivered as a conditioning dose 4 h before or after a 1 Gy challenge dose. In an attempt to explain these results, we performed temporal studies over a wide radiation dose range to determine if the inversion response was temporally different at different doses. pKZ1 mice were irradiated with a single whole-body X-ray dose of 0.01 mGy, 1 mGy or 1 Gy, and spleen sections were then analyzed for pKZ1 inversions at 7 h, 1 day or 7 days after exposure. No change in inversion frequency was observed at the 7 h time point at any dose. At day 1, an increase in inversions was observed in response to the 0.01 mGy dose, whereas a decrease in inversions below sham-treated frequency was observed for the 1 mGy dose. Inversion frequency for both doses returned to sham-treated inversion frequency by day 7. To our knowledge, this is the first reported study to examine the temporal nature of a radiation response spanning a wide dose range, including doses relevant to occupational exposure, and the results are dynamic and dose specific. The results suggest that inversions induced after low-dose irradiation are removed by homeostatic mechanisms within a short time frame, and underscore the importance of studying responses over a period of time when interpreting radiation effects. Refereed/Peer-reviewed

Near-perfect adherence to antiretroviral therapy (ART) is required to achieve the best possible prevention and treatment outcomes. Yet, there have been particular concerns about the challenges of adherence among patients living in resource-limited settings in sub-Saharan Africa. The primary objective of this study was to explore adherence in a low-resourced, rural community of high HIV prevalence in South Africa and to identify specific individual and structural factors that can either challenge or support adherence in this context. We applied digital stories as a qualitative research tool to gain insights into personal contexts of HIV and ART adherence. Through an inductive thematic analysis of twenty story texts, soundtracks and drawings, we explored experiences, understandings, and contexts of the participants and identified potential barriers and facilitators for those on lifelong treatment. We found that many of the stories reflected a growing confidence in the effectiveness of ART, which should be viewed as a key facilitator to successful adherence since this attitude can promote disclosure and boost access to social support. Nevertheless, stories also highlighted the complexity of the issues that individuals and households face as they deal with HIV and ART in this setting and it is clear that an overburdened local healthcare system has often struggled to meet the demands of a rapidly expanding epidemic and to provide the necessary medical and emotional support. Our analysis suggests several opportunities for further research and the design of novel health interventions to support optimal adherence. Firstly, future health promotion campaigns should encourage individuals to test together, or at least accompany each other for testing, to encourage social support from the outset. Additionally, home-based testing and ART club interventions might be recommended to make it easier for individuals to adhere to their treatment regimens and to provide a sense of support and solidarity.

The GCT (Gamma-ray Cherenkov Telescope) is a dual-mirror prototype of Small-Sized-Telescopes proposed for the Cherenkov Telescope Array (CTA) and made by an Australian-Dutch-French-German-Indian-Japanese-UK-US consortium. The integration of this end-to-end telescope was achieved in 2015. On-site tests and measurements of the first Cherenkov images on the night sky began on November 2015. This contribution describes the telescope and plans for the pre-production and a large scale production within CTA.

Changes in the volume and extent of land ice of the Svalbard archipelago have been the subject of considerable research since their sensitivity to changes in climate was first noted. However, the measurement of these changes is often necessarily based on point or profile measurements which may not be representative if extrapolated to a whole catchment or region. Combining high-resolution elevation data from contemporary laser-altimetry surveys and archived aerial photography makes it possible to measure historical changes across a glacier's surface without the need for extrapolation. Here we present a high spatial resolution time-series for six Arctic glaciers in the Svalbard archipelago spanning 1961 to 2005. We find high variability in thinning rates between sites with prevalent elevation changes at all sites averaging −0.59 ± 0.04 m a−1 between 1961–2005. Prior to 1990, ice surface elevation was changing at an average rate of −0.52 ± 0.09 m a−1 which decreased to −0.76 ± 0.10 m a−1 after 1990. Setting the elevation changes against the glaciers' altitude distribution reveals that significant increases in thinning rates are occurring most notably in the glaciers' upper reaches. We find that these changes are coincident with a decrease in winter precipitation at the Longyearbyen meteorological station and could reflect a decrease in albedo or dynamic response to lower accumulation. Further work is required to understand fully the causes of this increase in thinning rates in the glaciers' upper reaches. If on-going and occurring elsewhere in the archipelago, these changes will have a significant effect on the region's future mass balance. Our results highlight the importance of understanding the climatological context of geodetic mass balance measurements and demonstrate the difficulty of using index glaciers to represent regional changes in areas of strong climatological gradients.

Summary Background: Ibuprofen is widely available as an over-the-counter treatment for pain and fever. New formulations are now available, with varying pharmacokinetic profiles. However, few studies have been specifically designed to examine the relationship between ibuprofen plasma levels and onset of analgesia. This study aimed to determine a value, or range of values, for the blood plasma level of ibuprofen at which onset of analgesia could be expected. Methods: Placebo-controlled clinical trials, investigating the efficacy and pharmacokinetics of ibuprofen 200 mg and 400 mg, were identified. A retrospective posthoc analysis was performed on data from trials that incorporated time to perceived pain relief as an endpoint and the incidence of confirmed/unconfirmed perceptible pain relief was assessed. Mean ibuprofen blood plasma levels were computed at various time points using data from pharmacokinetic trials. Results: Two trials were identified with sufficient data to analyse time to onset of analgesia (Current Controlled Trials ISRCTN73768226, ISRCTN86009231). For 400 mg ibuprofen, the incidence of confirmed perceptible pain relief was significantly greater vs. placebo at 20 min post dosing (both studies). For 200 mg ibuprofen, significance was reached at 20 min (one study). In the 17 trials, with data on plasma concentrations for patients receiving 400 mg ibuprofen, the weighted mean value at 20 min post dosing was 8.4 μg/ml (95% confidence interval, 6.8–10.1). Conclusions: Results of this study provide useful information for the development of new ibuprofen formulations. Further prospective studies and studies using other endpoints to define efficacy and onset would be of interest.

The objective of this study was to review our pediatric emergency department's (ED's) utilization of computed tomography (CT) in the diagnosis of peritonsillar abscess (PTA) and treatment outcomes.This study used case series with chart review.From January 2007 to January 2009, 148 patients were seen in our ED for possible PTA. Mean age at presentation was 11.8 years (range, 10 months to 18 years); 81 (54.7%) of 148 were females. Computed tomography was ordered in 96 (64.9%) of 148 patients, of which 73 (49.3%) 148 were confirmed to have PTA. Mean age of patients who underwent CT was younger when compared with those who did not have CT performed (mean, 11 vs 13 years; P = 0.02). Unilateral PTA was found in 65 (43.9%) of 148, bilateral in 8 (5.4%) of 148, and intratonsillar in 25 patients (16.9%). Concomitant CT findings of parapharyngeal space involvement were found in 19 (12.8%), and retropharyngeal space involvement in 11 (7.4%). Admission was necessary for 104 (71.2%) of 148 patients, whereas 42 were discharged from the ED. Transoral needle aspiration and/or incision and drainage were performed in the ED in 41 patients, with purulence identified in 33 (80.5%) of 41. Rapid strep testing was positive in 40 (32%) of 124 patients tested. Operative treatment was necessary in 44 patients (29.7%), 34 underwent incision and drainage, and 10 underwent quinsy tonsillectomy.Computed tomography is commonly utilized in the ED for the evaluation of PTA and is ordered more often in younger children.

The growth, survival and tag retention of double-tagged [external FT4 lock-on (FT4) and internal passive integrated transponder (PIT)-tagged] Atlantic halibut Hippoglossus hippoglossus were compared to internal PIT-tagged controls in a randomized trial. The objective was to assess the suitability of these tags for monitoring the performance of individual fish in longitudinal trials under commercial cage-culture conditions in the lower Bay of Fundy, New Brunswick, Canada. The FT4 tags were chosen due to their similarity to tags used by investigators to track H. hippoglossus in the wild. A subset of the population randomly received an external FT4 tag inserted through the operculum and were monitored over a 1105 day period. The specific growth rate of FT4-tagged fish was significantly reduced in the first sea summer with no significant difference observed for the remainder of the trial. The differential growth in the first sea summer created a relative size advantage, permitting controls to increase in size significantly faster than FT4 fish in all subsequent periods. The FT4 tags did not significantly influence survival under normal commercial cage-culture conditions. Results, however, suggest that the survival of FT4-tagged H. hippoglossus may be compromised during stressful handling events. Tag retention of FT4 tags was acceptable with 76% of tags remaining at the end of the 1105 day trial. FT4 tags proved to be an effective method to identify individual H. hippoglossus, with the caveat that they seriously bias productivity measures in commercial research trials.

Our aim was to investigate the effect of active manuka honey on radiation-induced mucositis. A total of 131 patients diagnosed with head and neck cancer who were having radiotherapy to the oral cavity or oropharyngeal area were recruited into the study, and were randomly allocated to take either manuka honey or placebo (golden syrup) 20 ml 4 times daily for 6 weeks. Mucositis was assessed according to the Radiation Therapy Oncology Group (RTOG) scale at baseline, weekly during radiotherapy, and twice weekly thereafter until the mucositis resolved. The patient's weight was recorded at the same time as the mucositis was assessed. Throat swabs to identify bacterial or fungal infections were taken at baseline, and during and after radiotherapy. There was no significant difference between honey and golden syrup in their effects on mucositis. Active manuka honey did not improve mucositis, but both the honey and the syrup seemed to be associated with a reduction in bacterial infections. Compliance was a problem after the onset of mucositis, which may have affected the findings.

To evaluate the safety of tonsillectomy in a short-term medical mission setting.Retrospective chart review.Catholic mission hospital in Guatemala.During 7 consecutive annual mission trips from 2004 to 2010, patients received tonsillectomy and adenotonsillectomy. Established safety protocol requires candidates for tonsillectomy to agree to stay within 1 hour of the hospital for 10 days following the operation. This study includes all tonsillectomy patients regardless of age or indication for tonsillectomy. The primary outcome measures include posttonsillectomy hemorrhage, nasopharyngeal reflux, readmission for dehydration, and mortality. This is a novel study as the work performed by most short-term medical missions is unregulated and unevaluated.Medical charts were available for 197 (96.6%) of the 204 patients receiving tonsillectomy in the 7-year period; this was the only inclusion criterion. Ninety-nine (50.3%) patients had tonsillectomy concomitantly with adenoidectomy. Patients ranged in age from 3 to 66 years. The mean (SD) age was 17.2 (14.0) years. The study team found documentation of postoperative complications in 3 (1.5%) patients; 2 experienced postoperative hemorrhage, 1 within the first postoperative hour and 1 at 96 hours. The final patient returned to the hospital within 24 hours symptomatic for dehydration.The authors have evaluated a protocol for tonsillectomy patients in a specific setting and believe their data represent satisfactory outcomes for the reviewed patients. The generalizability of this information is uncertain, but safety protocols should be established on all short-term medical missions to prevent untoward complications.