bluuebunny/crossref_metadata_2025 huggingface dataset:
Population pharmacokinetics and pharmacodynamics of rivaroxaban in patients with non‐valvular atrial fibrillation: Results from ROCKET AF
Authors: Girgis I.G. , Patel M.R. , Peters G.R. , Moore K.T. , Mahaffey K.W. , Nessel C.C. , Halperin J.L. , Califf R.M. , Fox K.A.A. , Becker R.C.
Published: March 2014

Two once‐daily rivaroxaban dosing regimens were compared with warfarin for stroke prevention in patients with non‐valvular atrial fibrillation in ROCKET AF: 20 mg for patients with normal/mildly impaired renal function and 15 mg for patients with moderate renal impairment. Rivaroxaban population pharmacokinetic (PK)/pharmacodynamic (PD) modeling data from ROCKET AF patients (n = 161) are reported and are used to confirm established rivaroxaban PK and PK/PD models and to re‐estimate values of the models' parameters for the current AF population. An oral one‐compartment model with first‐order absorption adequately described rivaroxaban PK. Age, renal function, and lean body mass influenced the PK model. Prothrombin time and prothrombinase‐induced clotting time exhibited a near‐linear relationship with rivaroxaban plasma concentration; inhibitory effects were observed through to 24 hours post‐dose. Rivaroxaban plasma concentration and factor Xa activity had an inhibitory maximum‐effect (Emax) relationship. Renal function (on prothrombin time; prothrombinase‐induced clotting time) and age (on factor Xa activity) had moderate effects on PK/PD models. PK and PK/PD models were shown to be adequate for describing the current dataset. These findings confirm the modeling and empirical results that led to the selection of doses tested against warfarin in ROCKET AF.
Changes of seasonal morph development induced by surgical operations in pupae of the large map butterfly Araschnia burejana Bermer (Lepidoptera: Nymphalidae)
Authors: Yamashita Kae , Kanzaki Koji , Hinauchi Mami , Fujishima Tetsuro , Islam Abu Taher Md. Fayezul , Kitazawa Chisato , Endo Katsuhiko , Yamanaka Akira
Published: March 2014

The nymphalid butterfly Araschnia burejana and the papilionid butterfly Papilio xuthus exhibit seasonal diphenism comprising spring‐morphs that develop from diapause pupae and summer‐morphs that develop from non‐diapause pupae. The development of seasonal morphs in A. burejana is regulated by the timing of secretion of ecdysteroids for adult development, whereas that in P. xuthus is regulated by the secretion of summer‐morph‐producing hormone, which is present in the brains and is under control of the photoperiod. We investigated whether a cerebral factor derived from brains plays a significant role in the regulation of seasonal morph development in A. burejana using surgical operations. Pairs of chilled diapause pupae that had been chilled for more than 3 months at 4°C were joined surgically to each other and then developed into spring‐morph or spring‐like‐morph adults. Chilled diapause pupae that were joined with 1‐day‐old non‐diapause pupae developed into summer‐morph or summer‐like‐morph adults. When the brains of non‐diapause pupae were removed surgically 6–8 hr after pupation with and without injection of 20‐hydroxyecdysone, a large portion of them developed into spring‐morph or spring‐like‐morph adults, respectively. Furthermore, 90% of non‐diapause pupae developed into spring‐morph or spring‐like‐morph adults when the neck was ligated within 5 min after pupation. These results indicated that a cerebral factor showing summer‐morph‐producing hormone activity, which is secreted from the brain in the early pupal stage, in addition to 20‐hydroxyecdysone for adult development, play a significant role in the determination of summer‐morph development in non‐diapause pupae of A. burejana. J. Exp. Zool. 321A:276–282, 2014. © 2014 Wiley Periodicals, Inc.
An Overview of the Literature on the Synthetic Routes to Azolyloxadiazoles
Authors: Abdel‐Wahab Bakr F. , Mohamed Hanan A. , Khidre Rizk E. , El‐Mansy Mohamed F.
Published: March 2014

Published data on the methods of preparation of different azoles linked directly to oxadiazoles are described systematically. This review is divided into classes based on the number of heteroatoms in the azoles connected to oxadiazole ring, and the subtitles are divided according to the type of oxadiazoles isomer.
Prevalence of severe obstructive sleep apnea in pediatric adenotonsillectomy patients
Authors: Jiang Nancy , Muhammad Charise , Ho Yan , Del Signore Anthony G. , Sikora Andrew G. , Malkin Benjamin D.
Published: March 2014

Objectives/Hypothesis

To determine the prevalence of severe obstructive sleep apnea (OSA) in a pediatric population who underwent indicated surgery for sleep disordered breathing (SDB).

Study Design

Retrospective chart review.

Methods

We reviewed the charts of patients aged 2 to 18 years who underwent tonsillectomy or adenotonsillectomy over a 4‐year period. Indications for preoperative polysomnography (PSG), PSG results, and perioperative complications were recorded.

Results

Two hundred and thirty‐five patients were included in the final analysis. Of these, 160 patients had preoperative PSG performed. The overall prevalence of severe OSA was 38%. The prevalence in patients for whom preoperative PSG was indicated or for which it should have been advocated according to the American Academy of Otolaryngology—Head and Neck Surgery (AAO‐HNS) clinical practice guideline was 45% and 40%, respectively, whereas the prevalence in patients with no indication for preoperative PSG was 34%. There was no significant difference between groups (P = 0.39). The overall complication rate was 11%, with the rate being significantly lower (P = 0.0022) in patients who did not have preoperative PSG performed (0%) when compared to those who did (16%).

Conclusions

The prevalence of severe OSA in this pediatric population was high. Specifically, a significant percentage of children who would not have received preoperative PSG under the AAO‐HNS recommendations had severe OSA and were consequently admitted for overnight observation. Our results suggest that preoperative PSG should be obtained for all pediatric patients with sleep disordered breathing.

Level of Evidence

4. Laryngoscope, 124:1975–1978, 2014
Highly Aligned and Single‐Layered Hollow Fibrous Membranes Prepared from Polyurethane and Silica Blends Through a Two‐Fluid Coaxial Electrospun Process
Authors: Huang Yun‐Shao , Kuo Chi‐Ching , Shu Yao‐Chi , Jang Shin‐Cheng , Tsen Wen‐Chin , Chuang Fu‐Sheng , Chen Chien‐Chung
Published: March 2014

Highly aligned, single‐layered hollow fibrous membranes are prepared using two‐fluid coaxial electrospinning (ES). Polyethylene oxide (PEO) is used as the core, and polyurethane (PU) and blends of PU with silica (SiO2) are used as the shell to extract the PEO. The effects of the polymer‐complex concentration, the ES parameters, and the SiO2 blending ratio on the morphologies and mechanical properties of fibers are explored. Using an appropriate PU concentration and applied spinning voltage combination yields a high fiber‐alignment degree. The hollow fibrous average area increases as the inner‐to‐outer flow‐rate ratio (FRRi/o) increases because the inner flow increases. When using a PU concentration of 13 wt%, a spinning voltage of 7 kV, and an FRRi/o of 0.8, along with blending 15% SiO2 with PU, the fiber alignment of the PU/SiO2 membranes is 95%. The Young's modulus indicates that adding SiO2 enhances the mechanical properties, causing a monolayer hollow‐fiber assembly with interconnected fibers to form.

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PEG‐Amine‐Initiated Polymerization of Sarcosine N‐Thiocarboxyanhydrides Toward Novel Double‐Hydrophilic PEG‐b‐Polysarcosine Diblock Copolymers
Authors: Tao Xinfeng , Deng Chao , Ling Jun
Published: March 2014

Amino acid N‐thiocarboxyanhydride (NTA), the thioanalog of N‐carboxyanhydride (NCA), is much more stable than NCA against moisture and heat. The convenient monomer synthesis without rigorous anhydrous requirements makes the ring‐opening polymerization of NTA a competitive alternative to prepare polypeptoid‐containing materials with potential of large‐scale production. Polysarcosines (PSars) with high yields (>90%) and low polydispersities (<1.2) are synthesized from sarcosine N‐thiocarboxyanhydride (Sar‐NTA) at 60 °C initiated by primary amines including poly(ethylene glycol) amine (PEG–NH2). The lengths of PSar segments are controlled by various feed ratios of Sar‐NTA to initiator. PEG‐b‐PSar products, a class of novel double‐hydrophilic diblock copolymers, are effective in stabilizing oil‐in‐water emulsions at nano‐ and microscale, which demonstrates promising encapsulation applications in food, cosmetics, and drug delivery. Due to the different solubility of PEG and PSar blocks, PEG‐b‐PSar copolymers form micelles in organic solvents with the capability to incorporate metal cations including Cu2+ and Ni2+.

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Clinical, electrophysiological, and molecular findings in early onset hereditary neuropathy with liability to pressure palsy
Authors: Potulska‐Chromik Anna , Sinkiewicz‐Darol Elena , Ryniewicz Barbara , Lipowska Marta , Kabzińska Dagmara , Kochański Andrzej , Kostera‐Pruszczyk Anna
Published: March 2014

Introduction: The first episode of hereditary neuropathy with liability to pressure palsy (HNPP) in childhood is rare. Methods: We analyzed retrospectively the data of 7 patients with a deletion in PMP22 and onset of symptoms before age 18 years. Direct sequencing of the LITAF (lipopolysaccharide‐induced tumor necrosis factor) gene was performed in patients and family members. Results: Clinical presentations varied from mononeuropathies to brachial plexopathy, with recurrent episodes in 4 patients. Electrophysiological abnormalities characteristic for HNNP were found in most subjects. Analysis of the LITAF gene revealed an Ile92Val polymorphism in 6 of 7 (86%) probands and 5 of 7 (83%) family members, over 4 times greater frequency than in the general population. Conclusions: Clinical suspicion of HNPP even when nerve conduction study results do not fulfill HNPP criteria should indicate genetic testing. In our patients, early‐onset HNPP was associated frequently with isoleucine92valine LITAF polymorphism. Muscle Nerve 50: 914–918, 2014
Auf(zug) zu den Sternen
Authors: Waletzko Michael , Oppermann Raika
Published: March 2014

Lösen bald Kohlenstoffnanoröhren die Probleme der Raumfahrt? Ein Fahrstuhl ins Weltall an einem Kabel aus dem High‐Tech‐Material könnte die kostenintensive Raketentechnik ersetzen. Aber bislang ist es so, dass alle Stricke reißen …
Auf Resistenzen besser reagieren
Authors: Groß Michael
Published: March 2014

Der Nachschub an neuartigen antibakteriellen Wirkstoffen versiegt, und es gibt immer mehr resistente Erreger. Falsche und unnötige Verwendung von Antibiotika verschärft das Problem. Eine neue Strategie im Kampf mit Infektionskrankheiten beruht vielleicht auf Viren, welche die Bakterien infizieren.
Die Insel der Phasen
Authors: Daubenfeld Thorsten , Zenker Dietmar
Published: March 2014

Studenten beschäftigen sich oft erst kurz vor der Prüfung mit dem Lernstoff. Die physikalische Chemie als computerbasiertes Abenteuerspiel motiviert sie, das gesamte Semester hindurch zu lernen.
Conventional and molecular cytogenetic characterization of Burkitt lymphoma with bone marrow involvement in Brazilian children and adolescents
Authors: De Souza Mariana T. , Hassan Rocio , Liehr Thomas , Marques‐Salles Terezinha J. , Boulhosa Alice M. , Abdelhay Eliana , Ribeiro Raul C. , Silva Maria Luiza Macedo
Published: March 2014

Background

Burkitt lymphoma/leukemia (BL/L) is cytogenetically characterized by the t(8;14)(q24;q32) or its variants, t(2;8)(p11;q21), and t(8;22)(q24;q11.2), which juxtapose the MYC oncogene to one of the three immunoglobulin loci. The overall cure rate of BL/L in children is 70–90%, but patients diagnosed with advanced‐stage disease have a less favorable prognosis. It is possible that secondary chromosomal abnormalities contribute to this unfavorable prognosis via chemotherapy resistance, but the results of genetic studies have been inconsistent. This study aimed to identify and characterize secondary chromosomal abnormalities associated with the t(8;14) and its variants in children with French‐American‐British‐L3 leukemia or Burkitt lymphoma with bone marrow involvement at the time of diagnosis.

Procedure

Chromosome analysis was based on G‐banding. Fluorescence in situ hybridization technique was applied using IGH/MYC/CEP8 dual‐fusion and MYC break‐apart probes. Multicolor chromosome banding was performed according to standard protocol.

Results

We describe a group of BL/L with extreme adverse clinical outcome, in which secondary chromosomal abnormalities, particularly those involving the long arms of chromosomes 1 and 13, were found in 71% of cases. The IGH/MYC fusion showed molecular heterogeneity in 14% of cases and two cases exhibited three IGH/MYC fusion signals.

Conclusions

Secondary chromosomal abnormalities were found in a high proportion of patients. We observed an extent of IGH/MYC heterogeneity not previously reported in Burkitt lymphoma, including the novel finding of three fusion signals in two cases. Pediatr Blood Cancer 2014; 61:1422–1426. © 2014 Wiley Periodicals, Inc.
An automated, high‐throughput method for targeted quantification of intact insulin and its therapeutic analogs in human serum or plasma coupling mass spectrometric immunoassay with high resolution and accurate mass detection (MSIA‐HR/AM)
Authors: Peterman Scott , Niederkofler Eric E. , Phillips David A. , Krastins Bryan , Kiernan Urban A. , Tubbs Kemmons A. , Nedelkov Dobrin , Prakash Amol , Vogelsang Maryann S. , Schoeder Tara , Couchman Lewis , Taylor David R. , Moniz Cajetan F. , Vadali Gouri , Byram Gregory , Lopez Mary F.
Published: March 2014

The detection and quantification of insulin and its therapeutic analogs is important for medical, sports doping, and forensic applications. Synthetic variants contain slight sequence variations to affect bioavailability. To reduce sample handling bias, a universal extraction method is required for simultaneous extraction of endogenous and variant insulins with subsequent targeted quantification by LC‐MS. A mass spectrometric immunoassay (MSIA), a multiplexed assay for intact insulin and its analogues that couples immunoenrichment with high resolution and accurate mass (HR/AM) spectrometric detection across the clinical range is presented in this report. The assay is sensitive, selective, semi‐automated and can potentially be applied to detect new insulin isoforms allowing their further incorporation into second or third generation assays.
Inflammatory activity at school age in very low birth weight bronchopulmonary dysplasia survivors
Authors: Korhonen Päivi H. , Suursalmi Piia H. , Kopeli Tarja , Nieminen Riina , Lehtimäki Lauri , Luukkaala Tiina , Korppi Matti , Saari Antti , Moilanen Eeva , Tammela Outi K.T.
Published: March 2014

Objective

Airway inflammation is involved in the pathogenesis of bronchopulmonary dysplasia (BPD). The aim of the study was to evaluate the inflammatory activity in plasma and exhaled air in very low birth weight (VLBW) BPD survivors at school age.

Methods

Twenty‐one 6–14‐year‐old former VLBW (birth weight ≤1,500 g) children with severe radiographic BPD (radBPD), 19 without radBPD (nonBPD group) and 19 non‐asthmatic term controls underwent measurement of eosinophil cationic protein, IL‐6, IL‐8, adiponectin, adipsin, leptin, and resistin in plasma, leukotriene B4 and 8‐isoprostane in exhaled breath condensate, and NO in exhaled breath. Background data were obtained from patient records, clinical examination and parental questionnaire. Both univariate and multivariate models were applied in the statistical analysis.

Results

There were no significant differences between the groups in any of the inflammatory markers measured. Five (25%) radBPD and 2 (11%) nonBPD children reported asthma (P = 0.058). In logistic regression analysis, exposure to chorioamnionitis was associated with low IL‐8 (OR 29.0, 95% CI 3.27–258) and postnatal corticosteroid therapy with high adiponectin (OR 32.0, 95% CI 1.29–793). High body mass index standard deviation score (BMI‐SDS) was associated with high plasma adipsin (OR 2.47, 95% CI 1.07–5.75) and leptin (OR 5.76, 95%CI 1.83–18.2) levels.

Conclusions

The inflammatory activity seems to decrease by school age in VLBW BPD survivors. Chorioamnionitis and postnatal corticosteroid treatment may modulate the inflammatory responsiveness in VLBW subjects even up to school age. The respiratory outcome in VLBW infants might be improved by preventing excessive weight gain. Pediatr Pulmonol. 2015; 50:683–690. © 2014 Wiley Periodicals, Inc.
Elevated IL‐8, TNF‐α, and MCP‐1 in men with metastatic prostate cancer starting androgen‐deprivation therapy (ADT) are associated with shorter time to castration‐resistance and overall survival
Authors: Sharma Jaya , Gray Kathryn P. , Harshman Lauren C. , Evan Carolyn , Nakabayashi Mari , Fichorova Raina , Rider Jennifer , Mucci Lorelei , Kantoff Philip W. , Sweeney Christopher J.
Published: March 2014

BACKGROUND

Chemokines and cytokines have been implicated in progression to castration‐resistant prostate cancer (CRPC).

METHODS

Retrospective data were accessed from 122 men with serum samples drawn at a median of 0.5 months after starting ADT for metastatic prostate cancer. MCP‐1, IL‐1‐β, IL‐2, IL‐8, IL‐6, and TNF‐α levels were measured by multiplex electrochemiluminescence assays. A multivariable Cox model assessed the association of time to CRPC and overall survival by the protein levels and adjusted for clinical variables (age and prostate specific antigen (PSA) levels at start of ADT, race, ECOG status, and extent of metastases). Associations were reported as hazard ratio (HR) with 95% confidence interval (CI).

RESULTS

Median follow‐up and overall survival were 44 and 42.2 months, respectively. ECOG performance status (≥1 vs. 0) was negatively associated with overall survival [HR = 2.8 (1.1–7.0),P = 0.03], and PSA nadir < 0.2 was predictive of longer time to development of CRPC [HR = 0.3 (0.2–0.5),P < 0.0001]. The HR for time to CRPC by protein above the median was 1.4 (95% CI: 0.9, 2.2,P = 0.13) for IL‐8; 1.3 (95% CI: 0.8, 2,P = 0.18) for TNF‐α; 1.0 (95% CI: 0.7, 1.6,P = 0.95) for MCP‐1. The HR for median overall survival for protein levels above the median was: 1.9 (95% CI: 1.0, 3.5,P = 0.04) for IL‐8; 2.0 (95% CI: 1.1, 3.5,P = 0.02) for TNF‐α; 1.7 (95% CI: 1.7, 3.0,P = 0.08) for MCP‐1. There was no association with IL‐1‐β, IL‐2, or IL‐6.

CONCLUSION

Higher levels of inflammation‐associated cytokines correlate with poorer prostate cancer outcomes and may guide strategies to improve prostate cancer therapy.Prostate 74:820–828, 2014. © 2014 Wiley Periodicals, Inc.
Magnetism and magnetocaloric effect of Mn0.98Fe0.02CoGe
Authors: Ren Q. Y. , Hutchison W. D. , Wang J. L. , Pérez S. Muñoz , Cadogan J. M. , Campbell S. J.
Published: March 2014

The crystallographic and magnetic properties of Mn0.98Fe0.02CoGe have been investigated by X‐ray diffraction, dc magnetization and neutron diffraction over the temperature range 20–450 K. The temperature dependence of the phase fractions of the orthorhombic and hexagonal phases is described well by a Gaussian distribution. The Mn0.98Fe0.02CoGe sample exhibits a first‐order magneto‐structural transition centred at TMS ∼ 297 K of FWHM ∼37 K with a magnetic entropy change of −ΔSM = 24(1) J kg−1 K−1 for ΔB = 0–5 T. Neutron diffraction indicates a ferromagnetic orthorhombic structure below TMS with only the Mn carrying magnetic moment (3.98(6) µB) at 20 K. The sample is paramagnetic in the hexagonal phase above TMS.
A p‐type (Cu1−xAgx)2O oxide solution film with cuprite structure for enhanced hole concentration
Authors: Huang Qin , Wang Liu , Bi Xiaofang
Published: March 2014

(Cu1−xAgx)2O oxide films with cuprite structure are presented. The p‐type film demonstrates an exceptional increase in hole cconcentration up to 1.18 × 1021 cm−3 with increasing Ag to 33 at.%. It is revealed from high‐resolution transmission electron microscopy along with X‐ray diffraction analysis that the oxide remains a single phase with the Ag content up to 33 at.%. Raman spectroscopy measurements exhibit different symmetrical features for the oxide than those of Cu2O. This suggests that the valence‐band edge level can be raised as a result of the incorporation of Ag1+ into Cu2O, which is verified by the small acceptor ionization energy observed for the (Cu0.67Ag0.33)2O. In addition, the coexistence of Cu1+ and Ag1+ is shown to suppress variable‐range‐hopping conduction, demonstrating weakly degenerate semiconductor behavior.
Acoustic emission pronounced field‐induced response near critical point in Ba0.6Sr0.4TiO3 ferroelectrics
Authors: Dul'kin Evgeniy , Zhai Jiwei , Roth Michael
Published: March 2014

Ba0.60Sr0.40TiO3 ceramic ferroelectric (FE) has been investigated in the wide temperature range under a dc external electric field (E) by means of dedicated acoustic emission (AE) method. The Curie point Tc = 9 °C, as well as both the temperature points, characteristic of relaxor ferroelectrics (RFEs), Burns temperature Td = 283 °C and intermediate temperature T* = 182 °C have successfully been detected. Tc demonstrates a nontrivial behavior in dependence on E, i.e., initially it decreases, reaches a minimum of Tth = 1.2 °C at the small threshold field Eth = 0.75 kV cm−1, and then starts to increase similar to ordered FEs, as E increases. The AE count rate, accompanying this nontrivial behavior of Tc(E) dependence, exhibits a pronounced maximum ≈5.4 s−1 above Eth at the Em = 1.5 kV cm−1. Both, Td and T* demonstrate a dependence on E, too, as was recently observed in relaxor FEs PbSc0.5Nb0.5O3 [Dul'kin et al., J. Appl. Phys. 113, 054105 (2013)]. The AE pronounced maximum is explained to be a consequence of the giant piezoelectric coefficients intrinsic to BaxSr1−xTiO3 FEs.
Performance analysis of an opportunistic multi‐user cognitive network with multiple primary users
Authors: Khan Fahd Ahmed , Tourki Kamel , Alouini Mohamed‐Slim , Qaraqe Khalid A.
Published: March 2014

Consider a multi‐user underlay cognitive network where multiple cognitive users concurrently share the spectrum with a primary network with multiple users. The channel between the secondary network is assumed to have independent but not identical Nakagami‐m fading. The interference channel between the secondary users (SUs) and the primary users is assumed to have Rayleigh fading. A power allocation based on the instantaneous channel state information is derived when a peak interference power constraint is imposed on the secondary network in addition to the limited peak transmit power of each SU. The uplink scenario is considered where a single SU is selected for transmission. This opportunistic selection depends on the transmission channel power gain and the interference channel power gain as well as the power allocation policy adopted at the users. Exact closed form expressions for the moment‐generating function, outage performance, symbol error rate performance, and the ergodic capacity are derived. Numerical results corroborate the derived analytical results. The performance is also studied in the asymptotic regimes, and the generalized diversity gain of this scheduling scheme is derived. It is shown that when the interference channel is deeply faded and the peak transmit power constraint is relaxed, the scheduling scheme achieves full diversity and that increasing the number of primary users does not impact the diversity order. Copyright © 2014 John Wiley & Sons, Ltd.
Outcome of Tumor‐Specific Mesorectal Excision for Rectal Cancer: The Impact of Laparoscopic Resection
Authors: Mohamed Zakir K. , Law Wai Lun
Published: March 2014

Objective

The study aimed to compare the outcomes of laparoscopic and open resection for rectal cancer in 1,063 consecutive cases in a single center.

Methods

We performed an analysis of 11 years of experience in rectal cancer surgery and compared the outcome of laparoscopic and open surgery. Multivariate and subgroup analysis was performed to look at the effect of the level of tumor and stage of disease on short‐term outcomes like conversion rate, anastomotic leak rate, length of stay, complication rate, 30‐day mortality, and long‐term outcomes like local recurrence and survival.

Results

A total of 1,063 patients underwent rectal resection with 470 (44.2 %) patients undergoing the laparoscopic approach. Groups were comparable in terms of age, sex, or co‐morbidities, and the operating time was longer in the laparoscopic group (210 vs. 150 min; p value < 0.001). A conversion rate of 6.8 % was noted, with an anastomotic leak rate of 3.87 % in the open group and 2.97 % in the laparoscopic group. The laparoscopic group had a lower blood loss (100 vs. 350 ml; p < 0.001), lower complication rates, and shorter length of stay (6 vs. 9 days). The local recurrence rate was comparable, and the laparoscopic approach had better overall and cancer‐specific survival, even after adjusting for stages. The laparoscopic approach was an independent factor associated with better overall and cancer‐specific survival on multivariate analysis.

Conclusion

We confirmed the oncological safety of laparoscopic rectal cancer surgery. Laparoscopic surgery also showed superiority in the short‐term and long‐term outcomes of rectal cancer.
Amino acid supplementation enhances urokinase production by HT-1080 cells
Authors: Khaparde Shilpa S , Roychoudhury Pradip K
Published: March 2014

Medium optimization is an important strategy that can lead to several fold increase in the production of proteins in cell culture. However, the usual methods of medium optimization are complex and time consuming. Urokinase is a widely employed thrombolytic drug for the treatment of stroke. We describe here medium optimization for maximizing urokinase production by HT-1080 cells using supplementation of specific amino acids. The new specifically designed method resulted in 240 % increase in urokinase productivity.
Digit Replantation in Children: A Nationwide Analysis of Outcomes and Trends of 455 Pediatric Patients
Authors: Berlin Nicholas L. , Tuggle Charles T. , Thomson James G. , Au Alexander
Published: March 2014

Background

The short-term outcomes of pediatric digit replantation have been derived primarily from single-center/surgeon experience. The purpose of this study was to conduct a nationwide analysis of outcomes and trends of pediatric digit replantation as compared to adult patients.

Methods

Digit replantation patients were identified in the 1999–2011 Healthcare Cost and Utilization Project, Nationwide Inpatient Sample. Outcomes included in-hospital procedure-related and total complications, microvascular revision, amputation, and length of stay (LOS). Univariate and multivariate analyses were performed to compare pediatric and adult patients and to identify independent predictors of outcomes. The annual rate of replantation among pediatric digit amputation patients was evaluated over the study period. Results A total of 3,010 patients who underwent digit replantation were identified, including 455 pediatric patients. For all replantations, age ≤18 years was associated with a lower likelihood of suffering a total complication (odds ratio (OR) 0.66, P=0.006), requiring amputation (OR 0.62, P<0.001), and experiencing LOS >5 days (OR 0.77, P=0.019), after adjusting for comorbidity, amputation severity, digit type, number of replantations, and hospital characteristics. Similar associations were observed between patient age and replantation outcomes for single-finger replantations. The rate of pediatric replantation (range 16 to 27 %) remained consistent through the study period (incidence rate ratio 0.98, P=0.06).

Conclusions

The rate of pediatric replantation has been relatively low, being 27 % at most in a given year. Importantly, short-term outcomes are better in children than for adults, supporting the indication to perform replantation in this age group when the surgeon feels that replantation is feasible and safe.
A Simple Blind Tenolysis for Flexor Carpi Radialis Tendinopathy
Authors: Brink Peter R. G. , Franssen Bas B. G. M. , Disseldorp Dominique J. G.
Published: March 2014

Background

Flexor carpi radialis (FCR) tendinopathy is an entity with a chronic form (repetitiveness of work) and an acute form (acute overstretching of the wrist). Confirmation of this syndrome can be established by injection of a small amount of a local anesthetic in the sheet of the FCR at this tender point. Complete relieve of the symptoms after injection confirms the existence of a tendinopathy of the FCR. Whereas rest and/or local application of steroids do not have a persistent effect on the short term outcome, a tenolysis could be performed. Before performing a tenolysis underlying causes should be excluded or treated.

Methods

In this article a simple and save technique is described, using a small Beaver knife to open the osteofibrous tunnel of the flexor carpi radialis tendon, without opening the carpal tunnel.

Results

Relieve of complaints could be reached up to almost two third of all cases.

Conclusion

In cases in which non-operative treatment is not effective regarding FCR tendinopathy, a simple blind technique by opening the osteofibrous tunnel could be successful.
Relationship between gut microbiota and development of T cell associated disease
Authors: Kosiewicz Michele M. , Dryden Gerald W. , Chhabra Anita , Alard Pascale
Published: March 2014

The interplay between the immune response and the gut microbiota is complex. Although it is well‐established that the gut microbiota is essential for the proper development of the immune system, recent evidence indicates that the cells of the immune system also influence the composition of the gut microbiota. This interaction can have important consequences for the development of inflammatory diseases, including autoimmune diseases and allergy, and the specific mechanisms by which the gut commensals drive the development of different types of immune responses are beginning to be understood. Furthermore, sex hormones are now thought to play a novel role in this complex relationship, and collaborate with both the gut microbiota and immune system to influence the development of autoimmune disease. In this review, we will focus on recent studies that have transformed our understanding of the importance of the gut microbiota in inflammatory responses.
Functional intersection of Human Defensin 5 with the TNF receptor pathway
Authors: Lu Wuyuan , de Leeuw Erik
Published: March 2014

Defensins are cationic antimicrobial peptides that contribute to regulation of host cell function also. Here, we report on the regulation of cell death by Human Defensin 5, the major antimicrobial peptide of ileal Paneth cells. We find that Human Defensin 5‐mediated cellular effects depend on functional expression of Tumor Necrosis Factor receptors and downstream mediators of TNF signaling. Our data indicate the involvement of interactions between Human Defensin 5 and the extra‐cellular domain of Tumor Necrosis Factor receptor 1. Human Defensin‐5 also induces apoptosis intrinsically by targeting the mitochondrial membrane.
Targeted pancreatic cancer therapy with the small molecule drug conjugate SW IV‐134
Authors: Hashim Yassar M. , Spitzer Dirk , Vangveravong Suwanna , Hornick Mary C. , Garg Gunjal , Hornick John R. , Goedegebuure Peter , Mach Robert H. , Hawkins William G.
Published: March 2014

Pancreatic adenocarcinoma is highly resistant to conventional therapeutics and has been shown to evade apoptosis by deregulation of the X‐linked and cellular inhibitors of apoptosis proteins (XIAP and cIAP). Second mitochondria‐derived activator of caspases (Smac) induces and amplifies cell death by reversing the anti‐apoptotic activity of IAPs. Thus, Smac‐derived peptide analogues (peptidomimetics) have been developed and shown to represent promising cancer therapeutics. Sigma‐2 receptors are overexpressed in many proliferating tumor cells including pancreatic cancer. Selected ligands to this receptor are rapidly internalized by cancer cells. These characteristics have made the sigma‐2 receptor an attractive target for drug delivery because selective delivery to cancer cells has the potential to increase therapeutic efficacy while minimizing toxicity to normal tissues.

Here, we describe the initial characterization of SW IV‐134, a chemically linked drug conjugate between the sigma‐2 ligand SW43 and the Smac mimetic SW IV‐52 as a novel treatment option for pancreatic adenocarcinoma. The tumor killing characteristics of our dual‐domain therapeutic SW IV‐134 was far greater than either component in isolation or in an equimolar mix and suggests enhanced cellular delivery when chemically linked to the sigma‐2 ligand. One of the key findings was that SW IV‐134 retained target selectivity of the Smac cargo with the involvement of the NF‐κB/TNFα signaling pathway. Importantly, SW IV‐134 slowed tumor growth and improved survival in murine models of pancreatic cancer. Our data support further study of this novel therapeutic and this drug delivery strategy because it may eventually benefit patients with pancreatic cancer.
Context influences the processing of verb transitivity in French sentences: more evidence for semantic−syntax interactions
Authors: MAGNE CYRILLE , BESSON MIREILLE , ROBERT STÉPHANE
Published: March 2014

abstract

The influence of semantic context on verb argument structure processing was investigated in two experiments using both ERP and behavioral measures. Participants were presented with sentences ending with syntactically and/or semantically congruous or incongruous noun phrases and they were asked to judge the overall acceptability of the sentences. Syntactically incongruous sentences contained an intransitive verb followed by a direct object (e.g., *L’ennemi a conspiré (INTR) un complot *‘The enemy conspired a scheme’). In line with our hypothesis, results showed that the processing of syntactic incongruities was influenced by the degree of semantic congruency between the different sentence constituents (strong in Experiment 1 and weak in Experiment 2). Thus, the same syntactic incongruity was processed differently depending upon the semantic context of the sentence, thereby demonstrating the influence of semantic context on syntactic processing. We propose a linguistic account of the differential effects of verb transitivity as a function of the semantic context based upon Cognitive Construction Grammar and Frame Semantics.
Which Democracies Will Last? Coups, Incumbent Takeovers, and the Dynamic of Democratic Consolidation
Authors: Svolik Milan W.
Published: March 2014

This article develops a change-point model of democratic consolidation that conceives of consolidation as a latent quality to be inferred rather than measured directly. Consolidation is hypothesized to occur when a large, durable, and statistically significant decline in the risk of democratic breakdowns occurs at a well-defined point during a democracy's lifetime. This approach is applied to new data on democratic survival that distinguish between breakdowns due to military coups and incumbent takeovers. We find that the risk of an authoritarian reversal by either process differs both in its temporal dynamic and determinants. Crucially, new democracies consolidate against the risk of coups but not incumbent takeovers, suggesting that distinct mechanisms account for the vulnerability of new democracies to these alternative modes of breakdown.
Use of cheese whey for biomass production and spray drying of probiotic lactobacilli
Authors: Lavari Luisina , Páez Roxana , Cuatrin Alejandra , Reinheimer Jorge , Vinderola Gabriel
Published: March 2014

The double use of cheese whey (culture medium and thermoprotectant for spray drying of lactobacilli) was explored in this study for adding value to this wastewater. In-house formulated broth (similar to MRS) and dairy media (cheese and ricotta whey and whey permeate) were assessed for their capacity to produce biomass ofLactobacillus paracaseiJP1,Lb. rhamnosus64 andLb. gasseri37. Simultaneously, spray drying of cheese whey-starch solution (without lactobacilli cells) was optimised using surface response methodology. Cell suspensions of the lactobacilli, produced inin house-formulatedbroth, were spray-dried in cheese whey-starch solution and viability monitored throughout the storage of powders for 2 months.Lb. rhamnosus64 was able to grow satisfactorily in at least two of the in-house formulated culture media and in the dairy media assessed. It also performed well in spray drying. The performance of the other strains was less satisfactory. The growth capacity, the resistance to spray drying in cheese whey-starch solution and the negligible lost in viability during the storage (2 months), makesLb. rhamnosus64 a promising candidate for further technological studies for developing a probiotic dehydrated culture for foods, utilising wastewaters of the dairy industry (as growth substrate and protectant) and spray drying (a low-cost widely-available technology).
Increased severity of suicidal behavior in impulsive aggressive patients exposed to familial adversities
Authors: Lopez-Castroman J. , Jaussent I. , Beziat S. , Guillaume S. , Baca-Garcia E. , Genty C. , Olié E. , Courtet P.
Published: March 2014

Background

The mechanisms by which childhood abuse and family history of suicidal behavior (FHS) lead to an increased risk of suicidal behavior are still unknown. Impulsive aggression may play an intermediate role. We investigated whether greater scores for aggression and impulsivity might be associated with the effects of FHS and/or childhood abuse on the severity of suicidal behavior.

Method

We examined the scores of three scales measuring impulsive aggression in a sample of 696 suicide attempters. We compared the highest and lowest scores with regard to reports of childhood abuse and FHS using adjusted multinomial regression models. Genetic polymorphisms of the serotonergic system known to be associated with impulsive aggression were also analyzed.

Results

Patients with high impulsive aggressive scores showed significant differences in sociodemographic, clinical and suicidal features compared with patients with low impulsive aggressive scores. Adjusted results showed that combinations of some types of childhood abuse and FHS, particularly emotional abuse and emotional neglect, are associated with high impulsivity and hostility scores. The SS genotype of the serotonin transporter gene (5-HTTLPR) was associated with high levels of impulsivity when the subjects reported emotional abuse [odds ratio (OR) 5.55, 95% confidence interval (CI) 1.75–17.5] or physical abuse (OR 5.03, 95% CI 1.50–16.9) in their childhood.

Conclusions

Our results support the role of impulsive aggression as one of the links that may connect childhood abuse and FHS with severity of suicidal behavior.
Stepped care treatment delivery for depression: a systematic review and meta-analysis
Authors: van Straten A. , Hill J. , Richards D. A. , Cuijpers P.
Published: March 2014

Background

In stepped care models patients typically start with a low-intensity evidence-based treatment. Progress is monitored systematically and those patients who do not respond adequately step up to a subsequent treatment of higher intensity. Despite the fact that many guidelines have endorsed this stepped care principle it is not clear if stepped care really delivers similar or better patient outcomes against lower costs compared with other systems. We performed a systematic review and meta-analysis of all randomized trials on stepped care for depression.

Method

We carried out a comprehensive literature search. Selection of studies, evaluation of study quality and extraction of data were performed independently by two authors.

Results

A total of 14 studies were included and 10 were used in the meta-analyses (4580 patients). All studies used screening to identify possible patients and care as usual as a comparator. Study quality was relatively high. Stepped care had a moderate effect on depression (pooled 6-month between-group effect size Cohen'sdwas 0.34; 95% confidence interval 0.20–0.48). The stepped care interventions varied greatly in number and duration of treatment steps, treatments offered, professionals involved, and criteria to step up.

Conclusions

There is currently only limited evidence to suggest that stepped care should be the dominant model of treatment organization. Evidence on (cost-) effectiveness compared with high-intensity psychological therapy alone, as well as with matched care, is required.
Spectacle in the Theatre
Authors: Beckerman Bernard
Published: March 2014

In his history of the Crimean War Henry Tyrrell describes the victory celebration held in Green Park, London in 1856. The celebration began with a burst of color in the night sky. Then “for two hours, followed every conceivable design of elegant and dazzling pyrotechnic art. Flights of rockets, a hundred at a time; revolving wheels, suns, stars, golden streamers, and fiery serpents chas[ed] each other through the air.… The triumph, however, of the entertainment was reserved for the close of it.…” A stationary piece blazing and revolving fantastically, “exhibited the words ‘God save the Queen. … ‘”
The Foundation of the Royal Academy of Music in 1674 and Pierre Perrin's Ariane
Authors: Danchin Pierre
Published: March 2014

One of the more obscure episodes in the long history of the English stage is the foundation and short-lived existence of a French language Royal Academy of Music in the early 1670s. I intend to sum up here the evidence so far available and to show, using for the purpose a double MS. of Pierre Perrin's Ariane in the Bibliothèque Nationale, together with a few other documents, that the enterprise was indeed a very serious one, and was modelled on an earlier and very similar attempt in Paris a few years previously.
Pedro Calderon de la Barca and Madrid's Theatrical Calendar, 1700–1750: A Question of Priorities
Authors: Buck Donald C.
Published: March 2014

Until recently, the subject of Calderón's dominance of eighteenth-century popular theatre has been a closed case. What discussion there had been was centered on the heated polemics which surged during the second half of the century between the rabidly anti-Calderonian neo-classicists and the pro-Calderonian nationalists. Despite their conflicts over the literary and dramatic quality of his work, the general consensus on both sides was that Calderón's plays enjoyed widespread popularity among theatre-goers, and that his style influenced successive generations of dramatists throughout the century.
Penruddock Recreated: John Philip Kemble's Alterations of Cumberland's The Wheel of Fortune
Authors: Campbell Thomas J.
Published: March 2014

Since the publication of the John Philip Kemble Promptbooks in the Folger Library Series, it has been possible to determine both the extent and kind of changes made by Kemble in those roles most clearly associated with the great eighteenth-century actor-manager. Of these signature roles, perhaps none was so perfectly suited to his peculiar talents nor so universally acclaimed, by both his critics and supporters alike, as the role of Penruddock in Richard Cumberland's The Wheel of Fortune.
Determining the Date of Robert Hunter's Androboros
Authors: Davis Peter A.
Published: March 2014

The year 1714 has long been acknowledged as the publication date of America's earliest extant play, Androboros, a short and bawdy political farce by Col. Robert Hunter, governor of the New York colony from 1710 to 1719. Some scholars even go so far as to cite August 1, 1714 as the exact date, and not without good reason. The title page of the only known copy, now in the Huntington Library, clearly states: “Printed at Monoropolis since 1st August, 1714.” Such evidence would appear to be conclusive were it not for two references within the playscript itself that prove Androboros was written and printed no earlier than 1715.
Marked, transient, emotion-triggered QT accentuation in an adolescent female with type 1 long QT syndrome
Authors: Anderson Heather N. , Medford Beth A. , Ackerman Michael J.
Published: March 2014

Type 1 long QT syndrome is the most common long QT syndrome genetic subtype. Exercise and emotional stress can precipitate sudden cardiac events in patients with type 1 long QT syndrome; however, the precise mechanism remains elusive. We report the case of a teenage girl with type 1 long QT syndrome secondary to a rare frameshift mutation (p. L191fs+90X) in the KCNQ1-encoded Kv7.1 potassium channel. During emotional distress, her continuous QTc recordings precipitously increased, peaking within minutes to 669 ms and then returning to baseline (520 ms) as she calmed without concomitant increase in heart rate. This is the first described case documenting transient, marked accentuation of the QTc interval in a long QT syndrome patient during emotional distress. Such events may be triggered by transient accentuation of the intrinsic perturbation in cardiac repolarisation and increase the risk of degeneration to a ventricular arrhythmia. This case illustrates the need improved understanding of the complex interaction between emotion and cardiac stability in patients with long QT syndrome.
Long-Term Cognitive Correlates of Traumatic Brain Injury across Adulthood and Interactions with APOE Genotype, Sex, and Age Cohorts
Authors: Eramudugolla Ranmalee , Bielak Allison A.M. , Bunce David , Easteal Simon , Cherbuin Nicolas , Anstey Kaarin J.
Published: March 2014

There is continuing debate about long-term effects of brain injury. We examined a range of traumatic brain injury (TBI) variables (TBI history, severity, frequency, and age of injury) as predictors of cognitive outcome over 8 years in an adult population, and interactions with apolipoprotein E (APOE) genotype, sex, and age cohorts. Three randomly sampled age cohorts (20–24, 40–44, 60–64 years at baseline; N = 6333) were each evaluated three times over 8 years. TBI variables, based on self-report, were separately modeled as predictors of cognitive performance using linear mixed effects models. TBI predicted longitudinal cognitive decline in all three age groups. APOE ε4+ genotypes in the young and middle-aged groups predicted lower baseline cognitive performance in the context of TBI. Baseline cognitive performance was better for young females than males but this pattern reversed in middle age and old age. The findings suggest TBI history is associated with long-term cognitive impairment and decline across the adult lifespan. A role for APOE genotype was apparent in the younger cohorts but there was no evidence that it is associated with impairment in early old age. The effect of sex and TBI on cognition varied with age cohort, consistent with a proposed neuroprotective role for estrogen. (JINS, 2014, 20, 444–454)
Umgang mit chronischen körperlichen Erkrankungen
Authors: Bachmann Silke
Published: March 2014

Chronisch Erkrankte müssen sich mit zahlreichen Themen auseinandersetzen, die Krankheit selbst ist nur eines davon. Im Umgang erfordert dies einen Paradigmenwechsel im Gesundheitswesen: Es sind andere Haltungen und Interventionen als in der Akutmedizin gefordert. Krankheitsbewältigung ist kein einmaliger, endender Prozess, sondern durchläuft diverse Phasen, die sich wiederholen können (trajectory model). Somatisch Tätige unterstützen durch Kenntnis der allgemeinen und spezifischen Belastungsfaktoren (körperliche, emotionale, soziale Symptome/Einschränkungen), durch emotionale Zuwendung und Empathie, durch Respektieren des Individuums als Experten der eigenen Erkrankung sowie durch Aktivierung von Ressourcen und Selbstwirksamkeit. Wissen und Erfahrung der Behandler bestimmen die Grenzen im Umgang mit chronisch Erkrankten. Diese gilt es zu erkennen, um eigener Überforderung vorzubeugen. Hilfreich ist, Fachärzte/innen für Psychiatrie und Psychotherapie, Supervisionen oder Balintgruppen in Anspruch zu nehmen.