bluuebunny/crossref_metadata_2025 huggingface dataset:
Random versus Deterministic Descent in RNA Energy Landscape Analysis
Authors: Day Luke , Abdelhadi Ep Souki Ouala , Albrecht Andreas A. , Steinhöfel Kathleen
Published: March 2016

Identifying sets of metastable conformations is a major research topic in RNA energy landscape analysis, and recently several methods have been proposed for finding local minima in landscapes spawned by RNA secondary structures. An important and time-critical component of such methods is steepest, or gradient, descent in attraction basins of local minima. We analyse the speed-up achievable by randomised descent in attraction basins in the context of large sample sets where the size has an order of magnitude in the region of ~106. While the gain for each individual sample might be marginal, the overall run-time improvement can be significant. Moreover, for the two nongradient methods we analysed for partial energy landscapes induced by ten different RNA sequences, we obtained that the number of observed local minima is on average larger by 7.3% and 3.5%, respectively. The run-time improvement is approximately 16.6% and 6.8% on average over the ten partial energy landscapes. For the large sample size we selected for descent procedures, the coverage of local minima is very high up to energy values of the region where the samples were randomly selected from the partial energy landscapes; that is, the difference to the total set of local minima is mainly due to the upper area of the energy landscapes.
NLRP3 Inflammasome Plays an Important Role in the Pathogenesis of Collagen-Induced Arthritis
Authors: Zhang Yongfeng , Zheng Yi , Li Hongbin
Published: March 2016

Objective. To investigate the relationship between NLRP3 and the pathogenesis of collagen-induced arthritis.Methods. We used the collagen-induced arthritis (CIA) mouse model. The mice were divided into two groups: the model group (CIA,n=16) and the control group (Normal,n=8). The mice were sacrificed seven weeks after immunization. The arthritis score and imaging evaluation (X-rays, Micro-CT, and MRI) were performed. Synovial tissue NLRP3 expression and peripheral blood cytokine levels were analyzed.Results. The arthritis score (6.00 ± 2.52), imaging score (4.63 ± 0.92), and synovial tissue NLRP3 expression (4.00 ± 2.03) significantly increased in the CIA mice. The expression of synovial NLRP3 was positively correlated with arthritis clinical and radiographic scores (r=0.792andr=0.669, resp.).Conclusions. The synovial NLRP3 expression increased at the early onset of RA. Synovial NLRP3 expression level was correlated with the clinical arthritis severity and extent of radiological destruction, suggesting that NLRP3 is involved in the pathogenesis of RA.
Overtreatment and Cost-Effectiveness of the See-and-Treat Strategy for Managing Cervical Precancer
Authors: Nghiem Van T. , Davies Kalatu R. , Beck J. Robert , Follen Michele , Cantor Scott B.
Published: March 2016

Background: See-and-treat using loop electrosurgical excision procedure (LEEP) has been recommended as an alternative in managing high-grade cervical squamous intraepithelial lesions, but existing literature lacks evidence of the strategy's cost-effectiveness. We evaluated the overtreatment and cost-effectiveness of the see-and-treat strategy compared with usual care.

Methods: We modeled a hypothetical cohort of 40-year-old females who had not been screened for cervical cancer and followed them through their lifetimes using a Markov model. From a U.S. health-system perspective, the analysis was conducted in 2012 dollars and measured effectiveness in quality-adjusted life-years (QALY). We estimated incremental cost-effectiveness ratios (ICER) using a willingness-to-pay threshold of $50,000/QALY. The robustness of the see-and-treat strategy's cost-effectiveness and its overtreatment rates were further examined in various sensitivity analyses.

Results: In the base-case, the see-and-treat strategy yielded an ICER of $70,774/QALY compared with usual care. For most scenarios in the deterministic sensitivity analysis, this strategy had ICERs larger than $50,000/QALY, and its cost-effectiveness was sensitive to the disutility of LEEP treatment and biopsy-directed treatment adherence under usual care. Probabilistic sensitivity analysis showed that the see-and-treat strategy had a 50.1% chance to be cost-effective. It had an average overtreatment rate of 7.1% and a 78.8% chance to have its overtreatment rate lower than the 10% threshold.

Conclusion: The see-and-treat strategy induced an acceptable overtreatment rate. Its cost-effectiveness, compared with usual care, was indiscriminating at the chosen willingness-to-pay threshold but much improved when the threshold increased.

Impact: The see-and-treat strategy was reasonable for particular settings, that is, those with low treatment adherence. Cancer Epidemiol Biomarkers Prev; 25(5); 807–14. ©2016 AACR.
Comprehensive Genomic Profiling Identifies Frequent Drug-Sensitive EGFR Exon 19 Deletions in NSCLC not Identified by Prior Molecular Testing
Authors: Schrock Alexa B. , Frampton Garrett M. , Herndon Dana , Greenbowe Joel R. , Wang Kai , Lipson Doron , Yelensky Roman , Chalmers Zachary R. , Chmielecki Juliann , Elvin Julia A. , Wollner Mira , Dvir Addie , -Gutman Lior Soussan , Bordoni Rodolfo , Peled Nir , Braiteh Fadi , Raez Luis , Erlich Rachel , Ou Sai-Hong Ignatius , Mohamed Mohamed , Ross Jeffrey S. , Stephens Philip J. , Ali Siraj M. , Miller Vincent A.
Published: March 2016

Purpose: Reliable detection of drug-sensitive activating EGFR mutations is critical in the care of advanced non–small cell lung cancer (NSCLC), but such testing is commonly performed using a wide variety of platforms, many of which lack rigorous analytic validation.

Experimental Design: A large pool of NSCLC cases was assayed with well-validated, hybrid capture–based comprehensive genomic profiling (CGP) at the request of the individual treating physicians in the course of clinical care for the purpose of making therapy decisions. From these, 400 cases harboring EGFR exon 19 deletions (Δex19) were identified, and available clinical history was reviewed.

Results: Pathology reports were available for 250 consecutive cases with classical EGFR Δex19 (amino acids 743–754) and were reviewed to assess previous non-hybrid capture–based EGFR testing. Twelve of 71 (17%) cases with EGFR testing results available were negative by previous testing, including 8 of 46 (17%) cases for which the same biopsy was analyzed. Independently, five of six (83%) cases harboring C-helical EGFR Δex19 were previously negative. In a subset of these patients with available clinical outcome information, robust benefit from treatment with EGFR inhibitors was observed.

Conclusions: CGP identifies drug-sensitive EGFR Δex19 in NSCLC cases that have undergone prior EGFR testing and returned negative results. Given the proven benefit in progression-free survival conferred by EGFR tyrosine kinase inhibitors in patients with these alterations, CGP should be considered in the initial presentation of advanced NSCLC and when previous testing for EGFR mutations or other driver alterations is negative. Clin Cancer Res; 22(13); 3281–5. ©2016 AACR.
Clinical and Biologic Significance of MYC Genetic Mutations in De Novo Diffuse Large B-cell Lymphoma
Authors: Xu-Monette Zijun Y. , Deng Qipan , Manyam Ganiraju C. , Tzankov Alexander , Li Ling , Xia Yi , Wang Xiao-xiao , Zou Dehui , Visco Carlo , Dybkær Karen , Li Jun , Zhang Li , Liang Han , Montes-Moreno Santiago , Chiu April , Orazi Attilio , Zu Youli , Bhagat Govind , Richards Kristy L. , Hsi Eric D. , Choi William W.L. , van Krieken J. Han , Huh Jooryung , Ponzoni Maurilio , Ferreri Andrés J.M. , Parsons Ben M. , Møller Michael B. , Wang Sa A. , Miranda Roberto N. , Piris Miguel A. , Winter Jane N. , Medeiros L. Jeffrey , Li Yong , Young Ken H.
Published: March 2016

Purpose: MYC is a critical driver oncogene in many cancers, and its deregulation in the forms of translocation and overexpression has been implicated in lymphomagenesis and progression of diffuse large B-cell lymphoma (DLBCL). The MYC mutational profile and its roles in DLBCL are unknown. This study aims to determine the spectrum of MYC mutations in a large group of patients with DLBCL, and to evaluate the clinical significance of MYC mutations in patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) immunochemotherapy.

Experimental Design: We identified MYC mutations in 750 patients with DLBCL using Sanger sequencing and evaluated the prognostic significance in 602 R-CHOP–treated patients.

Results: The frequency of MYC mutations was 33.3% at the DNA level (mutations in either the coding sequence or the untranslated regions) and 16.1% at the protein level (nonsynonymous mutations). Most of the nonsynonymous mutations correlated with better survival outcomes; in contrast, T58 and F138 mutations (which were associated with MYC rearrangements), as well as several mutations occurred at the 3′ untranslated region, correlated with significantly worse survival outcomes. However, these mutations occurred infrequently (only in approximately 2% of DLBCL). A germline SNP encoding the Myc-N11S variant (observed in 6.5% of the study cohort) was associated with significantly better patient survival, and resulted in reduced tumorigenecity in mouse xenografts.

Conclusions: Various types of MYC gene mutations are present in DLBCL and show different impact on Myc function and clinical outcomes. Unlike MYC gene translocations and overexpression, most MYC gene mutations may not have a role in driving lymphomagenesis. Clin Cancer Res; 22(14); 3593–605. ©2016 AACR.
Naturally Occurring IgG Antibodies Provide Innate Protection against Vibrio cholerae Bacteremia by Recognition of the Outer Membrane Protein U
Authors: Aung Kyaw Min , Sjöström Annika E. , von Pawel-Rammingen Ulrich , Riesbeck Kristian , Uhlin Bernt Eric , Wai Sun Nyunt
Published: March 2016

Cholera epidemics are caused by Vibrio cholerae serogroups O1 and O139, whereas strains collectively known as non-O1/non-O139 V. cholerae are found in cases of extraintestinal infections and bacteremia. The mechanisms and factors influencing the occurrence of bacteremia and survival of V. cholerae in normal human serum have remained unclear. We found that naturally occurring IgG recognizing V. cholerae outer membrane protein U (OmpU) mediates a serum-killing effect in a complement C1q-dependent manner. Moreover, outer membrane vesicles (OMVs) containing OmpU caused enhanced survival of highly serum-sensitive classical V. cholerae in a dose-dependent manner. OMVs from wild-type and ompU mutant V. cholerae thereby provided a novel means to verify by extracellular transcomplementation the involvement of OmpU. Our data conclusively indicate that loss, or reduced expression, of OmpU imparts resistance to V. cholerae towards serum killing. We propose that the difference in OmpU protein levels is a plausible reason for differences in serum resistance and the ability to cause bacteremia observed among V. cholerae biotypes. Our findings provide a new perspective on how naturally occurring antibodies, perhaps induced by members of the microbiome, may play a role in the recognition of pathogens and the provocation of innate immune defense against bacteremia.
Endometrial Adenocarcinoma in SurePath™ Cervical Samples: Cytological Features Revisited
Authors: Gupta Nalini , Crossley John , Dudding Nick , Smith John H.F.
Published: March 2016

Objective: The cytomorphological criteria of malignant endometrial lesions in cervical samples are less well described than those of cervical lesions. We wished to investigate if there were features in SurePath™ liquid-based cytology samples that would facilitate more accurate differentiation between benign and malignant endometrial cells. Study Design: This was a two-phase study, with a review of all SurePath™ samples reported as endometrial adenocarcinoma (n = 42) evaluating 12 cytological features in the first phase. In phase 2 (test set), all initial cases plus an additional 83 cases were reviewed using these 12 cytological features to predict the outcome. Results: Out of 12 cytological features evaluated in phase 1 (training set), nuclear chromatin pattern, apoptotic bodies and tingible body macrophages were found to be the most significant features determining malignant histological outcome. These 12 cytological features were re-evaluated in phase 2 (n = 125). Of 125 cases, 54 had a benign and 71 had a malignant or premalignant histological outcome, with a positive predictive value of 56.8%. Conclusion: Granular nuclear chromatin, tingible body macrophages and apoptosis in the background are the most significant factors in determining whether endometrial cells present in cervical samples represent malignancy or are benign. Using these features, relatively accurate predictions of endometrial pathology can be made.
Utility of Prediction Scores for Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Treated with Nucleos(t)ide Analogues
Authors: Tawada Akinobu , Chiba Tetsuhiro , Saito Tomoko , Ogasawara Sadahida , Suzuki Eiichiro , Ooka Yoshihiko , Arai Makoto , Kanda Tatsuo , Shinozaki Masami , Goto Nobuaki , Nagashima Kengo , Yokosuka Osamu
Published: March 2016

Objective: The utility of risk scores to predict the development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with nucleos(t)ide analogue (NA) remains to be elucidated. Methods: CU-HCC (The Chinese University of Hong Kong-HCC) and GAG-HCC (Guide with Age, Gender, HBV DNA, Core promoter mutations and Cirrhosis) scores of 225 Japanese patients treated with NAs for at least 2 years were calculated before and 2 years after the NA treatment. According to the cutoff values, the patients were categorized into high-score or low-score groups. Results: Sixteen of 225 patients developed HCC. Patients with a high score before the NA treatment showed a significantly higher HCC incidence than those with a low score using both score models (p < 0.001). Time-dependent receiver operating characteristic analyses based on scores before and 2 years after the NA treatment showed that both models exhibited moderate accuracy in predicting HCC development. The HCC incidence was significantly lower in the patients whose scores decreased below the cutoff values in response to the NA treatment than in those whose scores remained high using both models (p < 0.01). Conclusions: The predictive performance of the CU-HCC and GAG-HCC scores in the CHB patients treated with NAs is comparable to that in the NA-naive patients. The patients with sustained high scores after the NA treatment showed a higher incidence of HCC development.
Timely Diagnosis of Acute Kidney Injury Using Kinetic eGFR and the Creatinine Excretion to Production Ratio, E/eG - Creatinine Can Be Useful!
Authors: Endre Zoltán H. , Pianta Timothy J. , Pickering John W.
Published: March 2016

Post transplant repeated measurements of urine volume and serum creatinine (sCr) are used to assess kidney function. Under non-steady state conditions, repeated measurement of sCr allows calculation of the kinetic estimated GFR (KeGFR). Additional measurement of urinary creatinine allows the calculation of the creatinine excretion to (estimated) production ratio (E/eG). We hypothesized that post-transplant KeGFR and E/eG would predict delayed graft function (DGF), as early as 4 h and outperform a validated clinical model at 12 h. This was a retrospective analysis of prospectively acquired data in a study of 56 recipients of deceased-donor kidney transplant. We assessed predictive performance with the area under the receiver operator characteristic curve (AUC) and the added value to a clinical model with integrated discrimination improvement analysis. At 4 h, the AUC for E/eG was 0.87 (95% CI 0.77-0.96) and for KeGFR 0.69 (95% CI 0.56-0.83). Both E/eG and KeGFR improved the risk prediction of a clinical model for DGF by 32 and 18%, and for non-DGF by 17 and 10%, respectively. While E/eG had better predictive performance of DGF than KeGFR, KeGFR might also facilitate perioperative management including drug dosing after kidney transplantation. Together these measurements may facilitate the possibility of conducting trials of early intervention to ameliorate the adverse effects of ischaemia-reperfusion injury on long-term DGF.
РОЗВИТОК ДІТЕЙ, НАРОДЖЕНИХ ІЗ ЗАСТОСУВАННЯМ ДОПОМІЖНИХ РЕПРОДУКТИВНИХ ТЕХНОЛОГІЙ: ПСИХОСОЦІАЛЬНІ АСПЕКТИ У ПЕРІОДІ ВАГІТНОСТІ ТА ОСОБЛИВОСТІ СТАНУ ЗДОРОВ’Я НА ПЕРШОМУ РОЦІ ЖИТТЯ
Authors: Synenko V. V.
Published: March 2016

Резюме. У роботі проведено аналіз захворюваності, динаміки психофізичного розвитку 28 дітей, народжених із застосуванням ДРТ, на першому році життя. Встановлено, що такі діти мають певні закономірності росту і розвитку, а також широкий спектр діагностованої патології. Паралельно проведено порівняльне обстеження вагітних жінок, які попередньо спостерігалися з приводу безпліддя, задля виявлення особливостей різних сфер життєдіяльності. Отримані дані дозволили зробити висновок щодо необхідності оптимізації спостереження дітей та жінок означених категорій.

 
Ключові слова: діти, допоміжні репродуктивні технології, психофізичний стан.
ДОСЛІДЖЕННЯ ЯКІСНИХ ОСОБЛИВОСТЕЙ ФАРМАЦЕВТИЧНОГО ЗАБЕЗПЕЧЕННЯ ХВОРИХ НА ЦИРОЗИ ПЕЧІНКИ ІЗ ВСТАНОВЛЕНИМИ УСКЛАДНЕННЯМИ ОСНОВНОГО ДІАГНОЗУ
Authors: Fedyak I. O. , Maksymenko О. V. , Sholoyko N. V.
Published: March 2016

РЕЗЮМЕ. У статті наведено результати частотного аналізу листків призначень хворих на цирози печінки різної етіології. Вони вказують, що препарати, які були спожиті пацієнтами в умовах стаціонару, насамперед призначалися для лікування ускладнень основного діагнозу. Встановлено, що гепатоцелюлярна недостатність різного ступеня спостерігалася у 94 % пацієнтів, портальна гіпертензія – у 87,4 %, асцит – у 37,9 %. Тому найчастіше призначали: Верошпірон (Gedeon Richter Plc., Угорщина) – отримали 64,2 % пацієнтів, Тіогама Турбо (Woerwag Pharma GmbH & Co. KG, Німеччина) – 45,8 % та Дуфалак (Solvay Pharmaceuticals B.V., Нідерланди) – 41 % хворих.

 

КЛЮЧОВІ СЛОВА: цирози печінки; ускладнення цирозу печінки; частотний аналіз; лікарські засоби, що застосовуються при захворюваннях печінки.
Ефективність відеоларингоскопу при анестезіологічному забезпеченні операцій у хворих на флегмону шиї
Authors: Artemenko V. Yu. , Budnyuk O. O.
Published: March 2016

У статті представлено результати анестезіологічного забезпечення 75 хворих на флегмону шиї. В проведеному дослідженні було встановлено, що основними причинами тяжкої інтубації трахеї у хворих з флегмоною шиї є: обмеження відкривання рота менше 3 см, набряк гортані і ригідний надгортанник при одонтогенній флегмоні порожнини рота і шиї. При інтубації трахеї за допомогою лампового ларингоскопа частота тяжких інтубацій становила 62,6 %, із них 9,3 % інтубацій були невдалими. Частота тяжких інтубацій трахеї при використанні фібробронхоскопа і відеоларингоскопа “Flaplight” склала 8,1 і 7,9 % відповідно порівняно з ламповим ларингоскопом. Таким чином, відеоларингоскоп Flaplight можна рекомендувати для інтубації трахеї у хворих з флегмоною шиї.
Activity of antioxidant enzymes and gelatinase in rats with epinephrine-induced miocardial ischemia
Authors: Parоnik V. A. , Shaulska O. E. , Zhylіuk V. I. , Shevtsova A. I.
Published: March 2016

In this study we examined the activity of antioxidant enzymes and gelatinases in rats with epinephrine-induced
myocardial ischemia and the impact of corvitin (C) and doxycycline (D) on these indicators. The administration
of epinephrine (0.2 mg/100 g) for 10 days leads to an increase in lipid peroxidation and to the elevated activity of
antioxidant enzymes and gelatinases in blood and in the heart of experimental animals. Under application of C and
D activity of the enzymes was reduced, especially activity of SOD and gelatinases. Our data suggest that C and D
can reduce the cardiotoxic effects of high doses of epinephrine due to their ability to bind free radicals and to inhibit
the activity of matrix-degrading enzymes.
Functional state of liver in cases of experimental hepatorenal syndrome in rats
Authors: Kulitska M. I.
Published: March 2016

During an experiment on white outbread mail rats with different models of hepatorenal syndrome, evaluations
of liver functional state biochemical findings in blood plasma were studied. The results of the study showed obvious
hepatic disorders manifested by decrease in blood plasma albumin and urea content, transaminitis, changes of
Ritis coefficient and increased alkaline phosphatase. It was determined that the disorders were more pronounced
in cases of hepatorenal syndrome modelling by means of carbon tetrachloride administering.
Emergency Cardiovascular Hospitalization Risk Attributable to Cold Temperatures in Hong Kong
Authors: Tian Linwei , Qiu Hong , Sun Shengzhi , Lin Hualiang
Published: March 2016

Background—

Associations between ambient temperature and cardiovascular morbidity have been well studied worldwide; however, few studies determined the cardiovascular disease burden attributable to temperature. We aimed to assess the risk attributed to temperature based on the exposure–lag–response relationship between temperature and circulatory diseases.

Methods and Results—

We collected daily time series data of emergency hospital admissions, mean temperature, and air pollution concentrations from January 2005 to December 2012 in Hong Kong. The association with temperature was modeled using a distributed lag nonlinear model integrated in quasi-Poisson regression. The cumulated effects of cold/hot temperature were abstracted. Attributable risk measures because of below optimal temperature (OT) were calculated to summarize the disease burden, and further separated into contributions from moderate and extreme cold temperatures. We observed significant nonlinear and delayed cold effect but no apparent hot effect lasting for 3 weeks on emergency circulatory hospitalizations. Compared with the identified OT at 23.0°C, the cumulative relative risk during 0 to 21 lag days was 1.69 (95% confidence interval, 1.56–1.82) for extreme cold (first percentile) and 1.22 (95% confidence interval, 1.15–1.29) for moderate cold temperature (10th percentile). Cold temperatures were responsible for temperature-related circulatory emergency hospitalizations, with attributable fraction of 6.33% for moderate cold and 0.82% for extreme cold while inducing 33 030 and 4257 cases, respectively. Several specific causes of cardiovascular diseases showed higher vulnerability.

Conclusions—

Moderate cold weather was responsible for a considerable attributable risk for cardiovascular diseases. The temperature-related hospitalizations risk found in this study may provide evidence for guiding the public health policies and preventions for cardiovascular diseases.
Stroke, Physical Function, and Death Over a 15-Year Period in Older Australian Women
Authors: Hubbard Isobel J. , Vo Kha , Forder Peta M. , Byles Julie E.
Published: March 2016

Background and Purpose—

As populations age, an increasing number of older women are living with stroke. This study looks at long-term outcomes for women with stroke, comparing mortality rates for women with poor physical function (PF) and those with higher levels of function. The purpose is to understand not only how long women might live after a stroke, but also how long they live with physical disability.

Methods—

The study uses 15 years of data on women from the Australian Longitudinal Study on Women’s Health 1921 to 1926 cohort. The risk of stroke and the risk of stroke and poor PF were estimated using Cox proportional hazard model. Among women who reported a stroke during the study period, mortality risk was compared according to their physical functioning level after that stroke.

Results—

Almost half of the women who had a stroke and poor PF survived past 10 years. The 10-year mortality rate was 37% for women with stroke and adequate PF and 51% for women with stroke and poor PF at the time of the stroke (hazard rate ratio, 1.52; 95% CI, 1.18–1.95;
P
=0.0015 adjusting for demographic and health covariates).

Conclusions—

This study provides evidence of the long-term outcomes of stroke among older women, with women living for many years with poor PF. This outcome has important implications for the women’s quality of life during their later years and in understanding the burden of disability associated with stroke.
Compartmentalization of an all-E. coli Cell-Free Expression System for the Construction of a Minimal Cell
Authors: Caschera Filippo , Noireaux Vincent
Published: March 2016

Cell-free expression is a technology used to synthesize minimal biological cells from natural molecular components. We have developed a versatile and powerful all-E. coli cell-free transcription–translation system energized by a robust metabolism, with the far objective of constructing a synthetic cell capable of self-reproduction. Inorganic phosphate (iP), a byproduct of protein synthesis, is recycled through polysugar catabolism to regenerate ATP (adenosine triphosphate) and thus supports long-lived and highly efficient protein synthesis in vitro. This cell-free TX-TL system is encapsulated into cell-sized unilamellar liposomes to express synthetic DNA programs. In this work, we study the compartmentalization of cell-free TX-TL reactions, one of the aspects of minimal cell module integration. We analyze the signals of various liposome populations by fluorescence microscopy for one and for two reporter genes, and for an inducible genetic circuit. We show that small nutrient molecules and proteins are encapsulated uniformly in the liposomes with small fluctuations. However, cell-free expression displays large fluctuations in signals among the same population, which are due to heterogeneous encapsulation of the DNA template. Consequently, the correlations of gene expression with the compartment dimension are difficult to predict accurately. Larger vesicles can have either low or high protein yields.
Overcoming the Gender Gap: The Possibilities of Alignment between the Responsibility to Protect and the Women, Peace and Security Agenda
Authors: Hewitt Sarah
Published: March 2016

This article examines the relationship between the Women, Peace and Security (wps) agenda and the Responsibility to Protect (R2P). R2P remains ‘gender-blind’, inadequately addressing gender issues encompassed within the wps agenda. Currently, women are limited by gendered structural inequalities and marginalisation in conflict, where the wps agenda has failed to be incorporated in R2P and broader conflict mechanisms. I argue that the wps agenda and R2P are mutually beneficial and complementary in their protection mandates to enable lasting peace. I identify three common intersecting commitments of these two normative frameworks to provide a more holistic, gender-sensitive approach to conflict. These are prevention and early warning systems, protection and gender-sensitive peacekeeping, and women’s participation in peace processes. I conclude that identifying common areas of engagement could potentially effect positive changes for women and men on the ground in conflict prevention and protection, and post-conflict reconstruction.
New species, new records and re-description of spider mites (Acari: Tetranychidae) from India
Authors: ZEITY MAHRAN , SRINIVASA N. , GOWDA C. CHINNAMADE
Published: March 2016

Two species of Tetranychidae (Acari), Oligonychus neotylus sp. nov. from Zea mays and Pennisetum purpureum (Poaceae) and Tetranychus hirsutus sp. nov. from Gymnema sylvestre R. Br. (Apocynaceae) are described from Karnataka state, south India. Tetranychus bambusae Wang and Ma is recorded for the first time from India and re-described. Four other species are reported for the first time from India viz., Oligonychus coniferarum (McGregor), Oligonychus duncombei Meyer, Tetranychus marianae McGregor and Tetranychus okinawanus Ehara from Cupressus sp., an undetermined grass, Centrosema pubescens and Adenium obesum, respectively.
A new species of Brasineura Silva-Neto & García Aldrete (Psocodea, ‘Psocoptera’, Ptiloneuridae), with comments on morphological variation in B. troglophilica and a revised generic diagnosis
Authors: NETO ALBERTO MOREIRA DA SILVA , ALDRETE ALFONSO N. GARCÍA , RAFAEL JOSÉ ALBERTINO
Published: March 2016

Brasineura serranortensis sp. n. is here described and illustrated. This is the third known species of Brasineura and differs from the other species in the genus in phallosome, hypandrium and paraproct structure. Comments on variation in fore wing venation, and new records for B. troglophilica are included. A revised generic diagnosis is also presented.
Georg Rasch and Benjamin Wright’s Struggle With the Unidimensional Polytomous Model With Sufficient Statistics
Authors: Andrich David
Published: March 2016

This article reproduces correspondence between Georg Rasch of The University of Copenhagen and Benjamin Wright of The University of Chicago in the period from January 1966 to July 1967. This correspondence reveals their struggle to operationalize a unidimensional measurement model with sufficient statistics for responses in a set of ordered categories. The article then explains the original approach taken by Rasch, Wright, and Andersen, and then how, from a different tack originating in 1961 and culminating in 1978, three distinct stages of development led to the current relatively simple and elegant form of the model. The article shows that over this period of almost two decades, the demand for sufficiency of a unidimensional parameter of the object of measurement, which enabled the separation of this parameter from the parameter of the instrument, drove the theoretical development of the model.
Mast Cells Contribute to Porphyromonas gingivalis–induced Bone Loss
Authors: Malcolm J. , Millington O. , Millhouse E. , Campbell L. , Adrados Planell A. , Butcher J.P. , Lawrence C. , Ross K. , Ramage G. , McInnes I.B. , Culshaw S.
Published: March 2016

Periodontitis is a chronic inflammatory and bone-destructive disease. Development of periodontitis is associated with dysbiosis of the microbial community, which may be caused by periodontal bacteria, such as Porphyromonas gingivalis. Mast cells are sentinels at mucosal surfaces and are a potent source of inflammatory mediators, including tumor necrosis factors (TNF), although their role in the pathogenesis of periodontitis remains to be elucidated. This study sought to determine the contribution of mast cells to local bone destruction following oral infection with P. gingivalis. Mast cell–deficient mice (KitW-sh/W-sh) were protected from P. gingivalis–induced alveolar bone loss, with a reduction in anti– P. gingivalis serum antibody titers compared with wild-type infected controls. Furthermore, mast cell–deficient mice had reduced expression of Tnf, Il6, and Il1b mRNA in gingival tissues compared with wild-type mice. Mast cell–engrafted KitW-sh/W-sh mice infected with P. gingivalis demonstrated alveolar bone loss and serum anti– P. gingivalis antibody titers equivalent to wild-type infected mice. The expression of Tnf mRNA in gingival tissues of KitW-sh/W-sh mice was elevated following the engraftment of mast cells, indicating that mast cells contributed to the Tnf transcript in gingival tissues. In vitro, mast cells degranulated and released significant TNF in response to oral bacteria, and neutralizing TNF in vivo abrogated alveolar bone loss following P. gingivalis infection. These data indicate that mast cells and TNF contribute to the immunopathogenesis of periodontitis and may offer therapeutic targets.
Amount and timing of group-based childcare from birth and cognitive development at 51 months
Authors: Barnes Jacqueline , Melhuish Edward C.
Published: March 2016

This study investigated whether the amount and timing of group-based childcare between birth and 51 months were predictive of cognitive development at 51 months, taking into account other non-parental childcare, demographic characteristics, cognitive development at 18 months, sensitive parenting and a stimulating home environment. Children’s ( N=978) cognitive development was assessed at 51 months with four subscales of the British Ability Scales: two verbal and two non-verbal. Mothers were interviewed and observed at 3, 10, 18, and 36 months and the quality of group care was assessed at 10, 18, and 36 months ( N=239) if it was used for ≥12 hours per week. Age of starting in group care and amount were highly associated ( r = -.75). Multiple regressions indicated that, controlling for other factors, higher cognitive development and particularly non-verbal ability was associated with more hours per week in group care from 0 to 51 months, or an earlier start, or group care before age 2. Nevertheless, the majority of variance was explained by other predictors: sex (girl), higher cognitive development at 18 months, older mother, first language English, mother of white ethnic background, with more qualifications, higher family social class, more maternal responsivity at 10 months and a more stimulating home learning environment (HLE) at 36 months. Hours per week in relative care or home-based care were not significant predictors of cognitive scores. For the smaller relatively advantaged sample who had group care quality information ( N=239), quality was a marginal predictor of better cognitive development but age of starting group care was not. Most variance was explained by 18 month cognitive development, maternal education, and family social class.
Investigating the Metabolic Syndrome
Authors: Zhang Xin , Lerman Lilach O.
Published: March 2016

The metabolic syndrome (MetS), a cluster of dyslipidemia, hypertension, and diabetes and an important contributor to cardiovascular morbidity and mortality, occurs in nearly 35% of adults and 50% of the aging population in the United States. However, the underlying mechanisms by which MetS orchestrates and amplifies cardiovascular events remain elusive. Furthermore, traditional therapeutic strategies addressing lifestyle modifications and individual components of MetS are often unsuccessful in decreasing morbidity due to MetS. The availability of an adequate experimental platform that mimics the complexity of MetS may allow development of novel management techniques. Swine models, including domestic pigs and minipigs, have made important contributions to our understanding of many aspects of MetS. Given their similarity to human anatomy and physiology, those models may have significant predictive power for elucidating the pathophysiology of MetS in a manner applicable to humans. Moreover, experimental maneuvers and drugs can be tested in these preclinical models before application in patients with MetS. This review highlights the utility of the pig as an animal model for metabolic disorders, which may play a crucial role in novel drug development to optimize management of MetS.
Acute Rhinosinusitis
Authors: Benninger Michael S. , Holy Chantal E. , Trask Douglas K.
Published: March 2016

Objective

Understand real‐world prescription patterns for patients presenting with a first diagnosis of ARS and evaluate adherence to published medical guidelines.

Study Design

Retrospective administrative database analysis.

Setting

US‐based outpatient settings.

Methods

From a US claims database (MarketScan), 99,033 patients were identified with acute rhinosinusitis (ARS) in 2012 (“index”), with a complete medical and prescription history for 12 months preindex and 18 months postindex and no diagnoses of asthma or chronic rhinosinusitis. Of these, a random 10,000‐patient sample was generated matched for age and sex to the initial cohort. Prescriptions and procedures at index, as well as complications up to 12 months postindex, were analyzed.

Results

Nearly 90% of all patients received a prescription at index. Antibiotics were prescribed for 84.8% patients, followed by antitussives (16.2% for adults, 6.2% for pediatrics), nasal corticosteroids (15.5% adults, 7.5% for pediatrics), and systemic corticosteroids (10.3% for adults, 5.5% for pediatrics), with 49% adults and 29% children receiving >1 medication at first visit. Macrolides were the most frequently prescribed antibiotics (35.6% adults, 28.6% pediatrics), followed by amoxicillin/clavulanate and amoxicillin. Within 12 months of index, 3 patients presented with meningitis and 3 with orbital cellulitis.

Conclusion

Significant variability in ARS treatment was observed, highlighting the need for heightened awareness of existing guidelines.
Quantitative Proteomics of Vestibular Schwannoma Cerebrospinal Fluid
Authors: Kazemizadeh Gol Mohammad Abraham , Lund Troy C. , Levine Samuel C. , Adams Meredith E.
Published: March 2016

This pilot study aimed to identify candidate proteins for future study that are differentially expressed in vestibular schwannoma (VS) cerebrospinal fluid (CSF) and to compare such proteins with those previously identified in perilymph and specimen secretions. CSF was collected intraoperatively prior to removal of untreated sporadic VS (3 translabyrinthine, 3 middle cranial fossa approaches) and compared with reference CSF samples. After proteolytic digestion and iTRAQ labeling, tandem mass spectrometry with ProteinPilot was used to identify candidate proteins. Of the 237 proteins detected, 13 were dysregulated in ≥3 of the 6 VS patients versus controls, and 13 were dysregulated (12 up, 1 down) in samples from patients with class D versus class B hearing. Four perilymph proteins of interest were dysregulated in ≥1 VS CSF samples. Thus, 26 candidate VS CSF biomarkers were identified that should be considered in future VS biomarker and tumor pathophysiology investigations.
Biofilm’s Role in Chronic Cholesteatomatous Otitis Media
Authors: Galli Jacopo , Calò Lea , Giuliani Monica , Sergi Bruno , Lucidi Daniela , Meucci Duino , Bassotti Ezio , Sanguinetti Maurizio , Paludetti Gaetano
Published: March 2016

Cholesteatoma is a destructive lesion involving the temporal bone, which may induce severe complications due to its expansion and erosion of adjacent structures. Bacterial biofilm plays a crucial role in the pathogenesis of many otolaryngologic inflammatory/infectious chronic diseases. In this pilot study, we investigated, by means of cultural examination and with scanning electron microscope, the presence of bacterial biofilm in a series of samples from the epitympanic and mastoid region in patients affected by cholesteatoma and from the promontory region in patients with healthy mucosa who were undergoing to stapes surgery. The preliminary data support the association between biofilm and cholesteatoma (81.3% of the cases) and allow us to hypothesize that keratinized matrix of cholesteatoma may represent the ideal substrate for biofilm colonization and survival; this finding is consistent with the clinical course of aural cholesteatoma, characterized by recurrent exacerbations and recalcitrant course.
A Systematic Review of Diuretics in the Medical Management of Ménière’s Disease
Authors: Crowson Matthew G. , Patki Aniruddha , Tucci Debara L.
Published: March 2016

Objective

(1) Review evidence for the use of oral diuretic medications in the management of Ménière’s disease. (2) Analyze therapy‐related hearing and vertigo outcomes.

Data Sources

Literature was obtained through directed searches of MEDLINE, EMBASE, Web of Science, EBSCO Host, Cochrane Reviews, and linked citations through seminal papers. We searched independent electronic databases for articles that reported the use of diuretics in patients with Ménière’s disease.

Review Methods

All articles of level 4 evidence or higher, per the Oxford Centre for Evidence‐Based Medicine, were included with no limit for number of patients, duration of therapy, or follow‐up period. Two independent investigators reviewed the articles for inclusion eligibility. Outcomes were tabulated, including subjective or quantitative measures of hearing, tinnitus, vertigo episode frequency, and medication adverse effects.

Results

Nineteen articles were included from 1962 to 2012 from 11 countries. Twelve retrospective case series, 4 randomized controlled trials, 2 case‐control trials, and 1 prospective case series were identified. Six studies investigated isosorbide; 5, hydrochlorothiazide; 2, acetazolamide; 2, chlorthalidone; and 1 each of betahistine, hydrochlorothiazide, chlorthalidone, acetazolamide, hydrochlorothiazide‐triamterene, and nimodipine. Eight (42.1%) studies reported hearing outcomes improvement. Fifteen (79.0%) studies reported vertigo outcomes improvement. Ten (52.6%) studies reported no side effects, and 4 studies (21.1%) reported abdominal discomfort. No significant morbidity or mortality was reported in any study.

Conclusion

Multiple low evidence–level studies report that oral diuretic therapy may be beneficial in the medical management of Ménière’s disease. Improvement in vertigo episode frequency was consistently reported, with less convincing evidence for improvement in hearing outcomes.
Endoscopic Transcanal Retrocochlear Approach to the Internal Auditory Canal with Cochlear Preservation
Authors: Kempfle Judith , Kozin Elliott D. , Remenschneider Aaron K. , Eckhard Andreas , Edge Albert , Lee Daniel J.
Published: March 2016

Contemporary operative approaches to the internal auditory canal (IAC) require the creation of large surgical portals for visualization with associated morbidity, including hearing loss, vestibular dysfunction, facial nerve injury, and skull base defects that increase the risk of cerebrospinal fluid leak. Transcanal approaches to the IAC have been possible only via a transcochlear technique. To preserve cochlear function, we describe a novel endoscopic transcanal infracochlear approach to the IAC in cadaveric temporal bones. Navigation fiducials were secured on fresh cadaveric heads, and real‐time computed tomography imaging was used for surgical guidance. With a combination of curved instruments and rigid angled endoscopy, a transcanal hypotympanotomy and subcochlear tunnel were created with superior extension to access the IAC. Postprocedure imaging and temporal bone dissection confirmed access to the IAC without injury to the cochlea or neighboring neurovascular structures.
Trends in the Incidence of Oropharyngeal Cancers in the United States
Authors: Enomoto Laura M. , Bann Darrin V. , Hollenbeak Christopher S. , Goldenberg David
Published: March 2016

Objective

The incidence of oropharyngeal squamous cell carcinoma (SCCa) has increased in the United States despite a decrease in tobacco usage, and it may be driven by an increase in oral human papilloma virus (HPV) infection. We studied the incidence of tongue base and tonsillar SCCa over time to understand the changing epidemiology of oropharyngeal SCCa.

Setting

Large national tumor registry.

Subjects and Methods

We studied patients diagnosed with oropharyngeal SCCa in SEER data (Surveillance, Epidemiology, and End Results) from 1973 to 2009. Age‐adjusted incidence rates standardized to the 2000 US population were computed, with stratifications for age, sex, race, and stage.

Results

The sample included 10,061 tongue base and 11,515 tonsillar oropharyngeal cancers. When stratified by age, the incidence of oropharyngeal SCCa in patients ≤55 years of age more than doubled over 30 years. While the incidence rate in females remained stable, the rate in males more than doubled, from 2 per 100,000 persons in 1973 to >4 per 100,000 persons in 2009. The age‐adjusted incidence of oropharyngeal SCCa in patients of black race/ethnicity remained consistently elevated, but the incidence in patients of white race/ethnicity rose from 1.3 per 100,000 persons to >2.5 per 100,000 persons, surpassing the incidence in black patients starting in 2002.

Conclusion

The observation that the incidence of oropharyngeal SCCa is increasing among younger white males, despite a reduction in tobacco usage in the United States, is consistent with HPV as the source. Primary and secondary prevention strategies may be warranted in this population.
Associations of Volume and Thyroidectomy Outcomes
Authors: Liang Tsung‐Jung , Liu Shiuh‐Inn , Mok King‐Tong , Shi Hon‐Yi
Published: March 2016

Objective

This study explored how different hospital volumes and surgeon volumes affect thyroidectomy outcomes in terms of length of stay (LOS), costs, and in‐hospital mortality.

Data Sources

MEDLINE and EMBASE databases.

Review Methods

This study retrospectively analyzed a cohort of 125,037 thyroidectomy patients treated at Taiwan hospitals from 1996 to 2010. Relationships between hospital/surgeon volume and patient outcomes were retrospectively analyzed by propensity score matching. In conjunction with the retrospective study, a systematic review and meta‐analysis of the relevant literature also were performed.

Results

The mean LOS for all thyroidectomies performed during the study period was 3.3 days, and the mean cost was $1193.5. Both high‐volume hospitals and high‐volume surgeons were associated with significantly shorter LOS and lower costs compared with their low‐volume counterparts (P <. 001). Different volume groups had similar in‐hospital mortality rates. The meta‐analysis results consistently showed that the benefits of high‐volume hospitals/surgeons are reduced LOS and costs. However, low in‐hospital mortality rates were associated with high‐volume surgeons but not with high‐volume hospitals.

Conclusions

This meta‐analysis showed that patients who received thyroidectomies performed by high‐volume hospitals and surgeons had shorter LOS and lower costs compared with those treated by low‐volume hospitals and surgeons. In addition, in‐hospital survival rates were better in patients treated by high‐volume surgeons. Further research is needed to define the learning curve for thyroidectomy and to clarify how hospital volume and surgeon volume affect its success rate.
A Charge Comparison of Audiometric Testing in the Pediatric Population
Authors: Trosman Samuel J. , Geelan‐Hansen Katie , Anne Samantha
Published: March 2016

Objective

To determine the charges associated with performing combined tympanometry and otoacoustic emissions vs a comprehensive audiogram in the pediatric population and to analyze its implications for future practice.

Study Design

Retrospective charge analysis.

Setting

Tertiary care academic center.

Subjects and Methods

Analysis was performed on 538 pediatric patients who underwent audiometric hearing testing from May through October 2014.

Results

In total, 401 patients had combined tympanometry and otoacoustic emissions testing and 91 patients underwent a comprehensive audiogram, while 46 patients underwent all 3 tests. The technical and professional charges for combined tympanometry and otoacoustic emissions were $139 and $116, respectively, with an overall charge of $255. The technical and professional charges for an audiogram were $124 and $198, respectively, with an overall charge of $322.

Conclusion

Objective testing with a combination of tympanometry and otoacoustic emissions charges insurers $67 less than an audiogram. Given the questionable reliability of behavioral audiometry in very young children, this is a factor to consider when choosing the appropriate test. With a large number of pediatric auditory hearing tests performed each year, the cost savings within the health care system could be substantial.