bluuebunny/crossref_metadata_2025 huggingface dataset:
Atopic dermatitis is not independently associated with nonfatal myocardial infarction or stroke among US women
Authors: Drucker A. M. , Li W.‐Q. , Cho E. , Li T. , Sun Q. , Camargo C. A. , Qureshi A. A.
Published: June 2016

We aimed to determine the association between atopic dermatitis (AD) and cardiovascular events in the Nurses' Health Study 2, a cohort of US women. We used logistic regression models to calculate age‐ and multivariate‐adjusted odds ratios (OR) and 95% confidence intervals (CI) for the associations between history of AD and nonfatal MI and nonfatal stroke. Of the 78 702 participants in our analysis, 7916 (10%) had a history of AD. There were 392 and 391 cases of nonfatal MI and stroke, respectively. AD was not associated with MI in age‐ or multivariate‐adjusted analyses. AD was significantly associated with stroke in the age‐adjusted analysis (OR 1.38, 95% CI 1.03–1.85). This was no longer significant in multivariate models that adjusted for hypertension, hypercholesterolemia and diabetes (OR 1.31, 95% CI 0.98–1.76) and atopic comorbidities (OR 1.17, 95% CI 0.86–1.58). AD was not independently associated with nonfatal MI or stroke in this study.
Liver stiffness measurement using acoustic radiation force impulse elastography in hepatitis C virus‐infected patients with a sustained virological response
Authors: Tachi Y. , Hirai T. , Kojima Y. , Miyata A. , Ohara K. , Ishizu Y. , Honda T. , Kuzuya T. , Hayashi K. , Ishigami M. , Goto H.
Published: June 2016

Background

Acoustic radiation force impulse (ARFI) elastography is a non‐invasive method for measuring liver stiffness. However, there are no reports evaluating the value of ARFI elastography for liver fibrosis in chronic hepatitis C patients with a sustained virological response (SVR).

Aim

To investigate the diagnostic performance of ARFI elastography for the assessment of liver fibrosis in hepatitis C virus (HCV) infected patients with an SVR.

Methods

In this prospective study, we enrolled 336 patients: 121 HCV patients with an SVR (44.6% women) and 215 patients with HCV (47.9% women). ARFI elastography measurements of all patients were performed on the same day of liver biopsy.

Results

The diagnostic accuracies, expressed as areas under the receiver operating characteristic curves for ARFI elastography, in HCV patients with an SVR and those in patients with HCV were 0.818 and 0.875 for the diagnosis of significant fibrosis (≥F2), 0.909 and 0.888 for the diagnosis of severe fibrosis (≥F3), and 0.981 and 0.890 for the diagnosis of liver cirrhosis (F4), respectively. The optimum cut‐off values for ARFI elastography were 1.26 m/s for ≥F2, 1.31 m/s for ≥F3 and 1.49 m/s for F4 in HCV patients with an SVR. The liver stiffness values were lower in patients with SVR compared with those in patients with HCV at the same stage of fibrosis. The liver stiffness values were affected by the necroinflammatory activity and the time after SVR.

Conclusion

Acoustic radiation force impulse elastography is an acceptable method for predicting the severity of fibrosis in patients with hepatitis C virus and a sustained viral response.
Comparative effectiveness of ledipasvir/sofosbuvir ± ribavirin vs. ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin in 6961 genotype 1 patients treated in routine medical practice
Authors: Backus L. I. , Belperio P. S. , Shahoumian T. A. , Loomis T. P. , Mole L. A.
Published: June 2016

Background

Real‐world data are needed to inform hepatitis C virus (HCV) treatment decisions.

Aim

To assess the comparative effectiveness of ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ± RBV) vs. ombitasvir/paritaprevir/ritonavir + dasabuvir (OPrD) ± RBV in genotype 1 HCV patients treated in routine medical practice.

Methods

Observational intent‐to‐treat cohort of genotype 1 patients initiating 8 or 12 weeks of LDV/SOF ± RBV or 12 weeks of OPrD ± RBV. Sustained virological response (SVR) required RNA below the limit of quantification at least 10 weeks after end of treatment.

Results

6961 patients initiated LDV/SOF (N = 4478), LDV/SOF + RBV (N = 1269), OPrD (N = 297), and OPrD + RBV (N = 917) at 126 facilities. Intention‐to‐treat SVR rates were 91.4% (3813/4170) for LDV/SOF, 90.0% (1098/1220) for LDV/SOF + RBV, 95.1% (269/283) for OPrD and 85.8% (746/869) for OPrD + RBV. SVR rates in those completing 8 weeks of LDV/SOF were 91.7% (1223/1333) and 12 weeks of LDV/SOF 94.6% (2475/2615), LDV/SOF + RBV 92.2% (1033/1120), OPrD 98.0% (248/253) and OPrD + RBV 95.5% (705/738). Significant predictors of SVR were African American race (OR 0.71, 95%CI 0.59–0.86, P < 0.001), body mass index (BMI) > 30 kg/m2 (OR 0.73, 95% CI 0.60–0.89, P = 0.002), FIB4 > 3.25 (OR 0.60, 95% CI 0.49–0.72, P < 0.001), OPrD + RBV compared to LDV/SOF (OR 0.60, 95% CI 0.48–0.76, P < 0.001) and subtype 1b (OR 1.38, 95% CI 1.11–1.71, P = 0.003). For those completing 12 weeks, FIB‐4 > 3.25 and high BMI remained significant predictors.

Conclusions

In this robust real‐world cohort, SVR rates were similar to clinical trials. FIB‐4 > 3.25 and high BMI were significant negative predictors of SVR. Reduced odds of SVR in African Americans and with OPrD + RBV likely arose from excess early discontinuation as these factors were no longer significant, when limited to patients completing a 12‐week course.
Vegetation assessment of native tree species in Broussonetia papyrifera‐dominated degraded forest landscape in southern Ghana
Authors: Agyeman Victor K. , Addo‐Danso Shalom D. , Kyereh Boateng , Abebrese Isaac K.
Published: June 2016

Question

Does the invasive tree species Broussonetia papyrifera facilitate the natural regeneration of native tree species in a degraded tropical forest landscape?

Location

Afram Headwaters Forest Reserve, southern Ghana.

Methods

We established sampling areas and assessed seedlings and saplings <5 cm DBH in nine habitats. The habitats were logging road, skid trail, large canopy gaps dominated by B. papyrifera, large canopy gaps dominated by invasive Chromolaena odorata, Nauclea diderrichii plantation, Mansonia altissima plantation, Terminalia ivorensis plantation, abandoned farmland and unlogged forest.

Results

We found that the abundance of pioneers declined with increasing abundance of B. papyrifera. This trend was more pronounced in the farmland and in the N. diderrichii plantation. By contrast, increased abundance of B. papyrifera did not lead to a decrease in the abundance of the shade‐tolerant species. B. papyrifera seedlings and saplings were absent in the forest understorey. We also found a lower abundance and richness of some vulnerable tree species and valuable timber species in the N. diderrichii plantation and in gaps dominated by B. papyrifera. However, we recorded both shade‐tolerant and shade‐intolerant species in the gaps dominated by B. papyrifera.

Conclusions

We found both shade‐tolerant and shade‐intolerant species in the B. papyrifera‐dominated gaps. This can provide a basis for future studies to explore the potential of such tree species in restoration programmes targeted at B. papyrifera‐invaded sites. Our results also suggest that the integrity of the undisturbed forest patches in the landscape must be protected to help prevent B. papyrifera from spreading further. We suggest further studies should be conducted at replicated sites with a similar habitat that represent varying levels of invasion by B. papyrifera to draw conclusions regarding the species’ potential to facilitate regeneration of native tree species.
Documents and Shifting Labor Environments Among Undocumented Migrant Workers in Northern California
Authors: Ordóñez Juan Thomas
Published: June 2016

This article explores the ways in which migrant workers establish particular relations to the state in shifting environments of criminalization and stigmatization that change the geography and nature of undocumented labor in the United States. Centering on Northern California, I address the results of the economic downturn between 2007 and 2009 for undocumented migrant men who had established jobs and paid taxes using fake Social Security cards, but whose labor conditions became unsustainable, leading many of them to turn to informal labor sites. I argue that work environments for many migrants shift to effectively ensure the marginalization of cheap labor, while maintaining their contributions to local economies and accommodating to the political constraints of the moment. I follow accounts of counterfeit identification, mainly fake Social Security cards, in labor practices that inscribe migrant laborers into the “system” they are supposed to be abusing, but to which they actually contribute a great deal through mimetic articulations of citizenship. I show how severing such ties becomes necessary in times of economic crisis and heighted criminalization, and I illustrate the ways in which real and imagined state repression make what Nicholas De Genova (2002) has called “deportability” an effective way to control and maintain an undocumented labor force within the boundaries of the country.
Mood stabilizers during breastfeeding: a systematic review of the recent literature
Authors: Uguz Faruk , Sharma Verinder
Published: June 2016

Objective

This review examined the safety of mood stabilizers in exposed breastfed infants.

Methods

PubMed was searched for English language reports between 1 January 1995 and 30 August 2015 by using combinations of key words breastfeeding, lactation, postpartum period, puerperium, mood stabilizers, lithium, lamotrigine, valproate, carbamazepine, and oxcarbazepine. Case reports, case series, and prospective or cross‐sectional studies including relevant data such as relative infant dose, milk‐to‐plasma ratio, infant drug plasma levels, and adverse events were identified.

Results

A total of 26 of 604 relevant reports in PubMed were included in the study. These reports included lamotrigine (122 cases in 12 reports), lithium (26 cases in five reports), carbamazepine (64 cases in five reports), valproate (nine cases in three reports), and oxcarbazepine (two cases in two reports). Of 26 reports, one report included both carbamazepine and valproate. The reports suggest that a considerable amount of lithium and lamotrigine are excreted into breast milk. There is a paucity of data on valproate and oxcarbazepine; however, the infant/maternal ratio of serum drug concentration seems to be lower in valproate exposure compared to other mood stabilizers. The incidence of adverse events in infants exposed to mood stabilizers is reported to be very low.

Conclusions

The current data suggest that mood stabilizers can be prescribed without any adverse events in most infants in lactating women. The available reports also suggest a low prevalence rate of laboratory abnormalities including hepatic, kidney, and thyroid functions in the infants. Additional studies examining short‐term and especially long‐term effects of mood stabilizers on breastfed infants are required.
Post‐thaw viability of cryopreserved peripheral blood stem cells (PBSC) does not guarantee functional activity: important implications for quality assurance of stem cell transplant programmes
Authors: Morgenstern Daniel A. , Ahsan Gulrukh , Brocklesby Margaret , Ings Stuart , Balsa Carmen , Veys Paul , Brock Penelope , Anderson John , Amrolia Persis , Goulden Nicholas , Cale Catherine M. , Watts Michael J.
Published: June 2016

Standard quality assurance (QA) of cryopreserved peripheral blood stem cells (PBSC) uses post‐thaw viable CD34+ cell counts. In 2013, concerns arose at Great Ormond Street Hospital (GOSH) about 8 patients with delayed engraftment following myeloablative chemotherapy with cryopreserved cell rescue, despite adequate post‐thaw viable cell counts in all cases. Root cause analysis was undertaken; investigations suggested the freeze process itself was a contributing factor to suboptimal engraftment. Experiments were undertaken in which a single PBSC product was divided into three and cryopreserved in parallel using a control‐rate freezer (CRF) or passive freezing method (−80°C freezer) at GOSH, or the same passive freezing at another laboratory. Viable CD34+ counts were equivalent and adequate in each. Granulocyte‐monocyte colony‐forming unit assays demonstrated colonies from the products cryopreserved using passive freezing (both laboratories), but no colonies from products cryopreserved using the CRF. The CRF was shown to be operating within manufacturer's specifications with freeze‐profile within acceptable limits. This experience has important implications for quality assurance for all transplant programmes, particularly those using cryopreserved products. The failure of post‐thaw viable CD34+ counts, the most widely used routine QA test available, to ensure PBSC function is of great concern and should prompt reassessment of protocols and QA procedures.
Phase Ib trial of the PI3K/mTOR inhibitor voxtalisib (SAR245409) in combination with chemoimmunotherapy in patients with relapsed or refractory B‐cell malignancies
Authors: Awan Farrukh T. , Gore Lia , Gao Lei , Sharma Jyoti , Lager Joanne , Costa Luciano J.
Published: June 2016

This phase Ib, dose‐escalation study investigated the maximum tolerated dose (MTD), recommended phase II dose (RP2D), safety, pharmacokinetics (PK) and preliminary efficacy of the pan‐class I phosphoinositide 3‐kinase (PI3K) and mechanistic target of rapamycin (mTOR) inhibitor voxtalisib [30 or 50 mg twice daily (BID)], in combination with rituximab (voxtalisib+rituximab) or rituximab plus bendamustine (voxtalisib+rituximab+bendamustine), in relapsed or refractory indolent B‐cell non‐Hodgkin lymphoma (NHL), mantle cell lymphoma and chronic lymphocytic leukaemia (CLL). MTD and RP2D of voxtalisib were determined using a 3 + 3 dose‐escalation design. Adverse events (AEs), plasma PK and disease response were recorded. Thirty‐seven patients were enrolled. The RP2D of voxtalisib in combination with rituximab or rituximab+bendamustine was 50 mg BID. Four patients experienced a total of five dose‐limiting toxicities. The most frequent AEs were nausea (45·9%), fatigue (37·8%) headache (32·4%) and pyrexia (32·4%). The most frequent grade ≥3 AEs were neutropenia (27·0%), thrombocytopenia (24·3%), anaemia (16·2%) and febrile neutropenia (10·8%). Voxtalisib PK parameters were not affected by co‐administration with rituximab or rituximab+bendamustine. Of 35 efficacy‐evaluable patients, four (11·4%) achieved complete response and 13 (37·1%) achieved partial response. Voxtalisib, in combination with rituximab or rituximab+bendamustine, demonstrated an acceptable safety profile and encouraging anti‐tumour activity in relapsed or refractory B‐cell malignancies.
Recent advances in therapy of chronic lymphocytic leukaemia
Authors: Routledge David J. M. , Bloor Adrian J. C.
Published: June 2016

The last 5 to 10 years have been marked by considerable advances in both our understanding of the biology and treatment of chronic lymphocytic leukaemia (CLL). Fludarabine‐based immuno‐chemotherapy is the current standard of care for first line therapy in younger fit patients and although this can be highly effective its use in older co‐morbid patients is limited by toxicity, and the prognosis for patients with high risk or fludarabine‐refractory disease is poor. The introduction of new antibodies has however, facilitated the use of immuno‐chemotherapy in co‐morbid patients. Beyond this, the recognition that CLL cells are critically dependent on B‐cell receptor (BCR) signalling and interactions with the cellular micro‐environment for proliferation and survival has led to the investigation of BCR inhibitors in CLL treatment. These have been shown to be highly effective although a number of questions remain about how they should be optimally used in clinical practice.
Antitumor effect of novel anti‐podoplanin antibody NZ‐12 against malignant pleural mesothelioma in an orthotopic xenograft model
Authors: Abe Shinji , Kaneko Mika Kato , Tsuchihashi Yuki , Izumi Toshihiro , Ogasawara Satoshi , Okada Naoto , Sato Chiemi , Tobiume Makoto , Otsuka Kenji , Miyamoto Licht , Tsuchiya Koichiro , Kawazoe Kazuyoshi , Kato Yukinari , Nishioka Yasuhiko
Published: June 2016

Podoplanin (aggrus) is highly expressed in several types of cancers, including malignant pleural mesothelioma (MPM). Previously, we developed a rat anti‐human podoplanin mAb, NZ‐1, and a rat–human chimeric anti‐human podoplanin antibody, NZ‐8, derived from NZ‐1, which induced antibody‐dependent cellular cytotoxicity (ADCC) and complement‐dependent cytotoxicity against podoplanin‐positive MPM cell lines. In this study, we showed the antitumor effect of NZ‐1, NZ‐8, and NZ‐12, a novel rat–human chimeric anti‐human podoplanin antibody derived from NZ‐1, in an MPM orthotopic xenograft SCID mouse model. Treatment with NZ‐1 and rat NK (CD161a+) cells inhibited the growth of tumors and the production of pleural effusion in NCI‐H290/PDPN or NCI‐H226 orthotopic xenograft mouse models. NZ‐8 and human natural killer (NK) (CD56+) cells also inhibited tumor growth and pleural effusion in MPM orthotopic xenograft mice. Furthermore, NZ‐12 induced potent ADCC mediated by human MNC, compared with either NZ‐1 or NZ‐8. Antitumor effects were observed following treatment with NZ‐12 and human NK (CD56+) cells in MPM orthotopic xenograft mice. In addition, combined immunotherapy using the ADCC activity of NZ‐12 mediated by human NK (CD56+) cells with pemetrexed, led to enhanced antitumor effects in MPM orthotopic xenograft mice. These results strongly suggest that combination therapy with podoplanin‐targeting immunotherapy using both NZ‐12 and pemetrexed might provide an efficacious therapeutic strategy for the treatment of MPM.
Evaluation of the inhibitory activity of (aza)isoindolinone‐type compounds: toward in vitro InhA action, Mycobacterium tuberculosis growth and mycolic acid biosynthesis
Authors: Chollet Aurélien , Stigliani Jean‐Luc , Pasca Maria Rosalia , Mori Giorgia , Lherbet Christian , Constant Patricia , Quémard Annaïk , Bernadou Jean , Pratviel Geneviève , Bernardes‐Génisson Vania
Published: June 2016

Inhibitors of the Mycobacterium tuberculosis enoyl‐ACP reductase (InhA) are considered as potential promising therapeutics for the treatment of tuberculosis. Previously, we reported that azaisoindolinone‐type compounds displayed, in vitro, inhibitory activity toward InhA. Herein, we describe chemical modifications of azaisoindolinone scaffold, the synthesis of 15 new compounds and their evaluations toward the in vitro InhA activity. Based on these results, a structure–InhA inhibitory activity relationship analysis and a molecular docking study, using the conformation of InhA found in the 2H7M crystal structure, were carried out to predict a possible mode of interaction of the best (aza)isoindolinone‐type inhibitors with InhA in vitro. Then, the work was extended toward evaluations of these compounds against Mycobacterium tuberculosis (Mtb) growth, and finally, some of them were also investigated in respect of their ability to inhibit mycolic acid biosynthesis inside mycobacteria. Although, some azaisoindolinones were able to inhibit InhA activity and Mtb growth in vitro, they did not inhibit the mycolic acid biosynthesis inside Mtb.
Mortality and cancer incidence among patients treated with recombinant growth hormone during childhood in Israel
Authors: Libruder Carmit , Blumenfeld Orit , Dichtiar Rita , Laron Zvi , Zadik Zvi , Shohat Tamy , Afek Arnon
Published: June 2016

Context

The inconclusive evidence regarding long‐term safety of recombinant human growth hormone (rhGH) therapy underlines the need for long‐term large‐scale cohorts.

Objective

To assess long‐term mortality and cancer incidence among patients treated with rhGH during childhood in Israel.

Design

A population‐based cohort study.

Setting

Data were retrieved from a national register established in 1988. Mortality data from the national population register were available through 31 December 2014. Data on cancer incidence from the national cancer registry were available through 31 December 2012.

Participants

All patients ≤19 years approved for rhGH treatment during 1988–2009 were included. Patients were assigned to three risk categories, according to the underlying condition leading to growth disorder.

Main outcome measures

All‐cause mortality and cancer incidence rates were calculated, based on person‐years at risk. Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) were calculated, using the Israeli general population as a reference.

Results

Included were 1687 patients assigned to the low‐risk category and 440 patients assigned to the intermediate‐risk category. In the low‐risk category, all‐cause mortality and cancer incidence were not significantly different than expected (SMR 0·81, 95% CI 0·22–2·08 and SIR 0·76, 95% CI 0·09–2·73). In the intermediate‐risk category, all‐cause mortality and cancer incidence were significantly higher than expected (SMR 4·05, 95% CI 1·62–8·34 and SIR 4·52, 95% CI 1·22–11·57).

Conclusions

No increased risk of mortality or cancer incidence was found in low‐risk patients treated with rhGH during childhood. Patients with prior risk factors were at higher risk of both mortality and cancer.
Functional characterization of two novel germline mutations of the KCNJ5 gene in hypertensive patients without primary aldosteronism but with ACTH‐dependent aldosterone hypersecretion
Authors: Sertedaki Amalia , Markou Athina , Vlachakis Dimitrios , Kossida Sophia , Campanac Emilie , Hoffman Dax A. , Sierra Maria De La Luz , Xekouki Paraskevi , Stratakis Constantine A. , Kaltsas Gregory , Piaditis George P. , Chrousos George P. , Charmandari Evangelia
Published: June 2016

Background

Germline mutations of the KCNJ5 gene encoding Kir3·4, a member of the inwardly rectifying K+ channel, have been identified in ‘normal’ adrenal glands, patients with familial hyperaldosteronism (FH) type III, aldosterone‐producing adenomas (APAs) and sporadic cases of primary aldosteronism (PA).

Objective

To present two novel KCNJ5 gene mutations in hypertensive patients without PA, but with Adrenocorticotropic hormone (ACTH)‐dependent aldosterone hypersecretion.

Design and Patients

Two hypertensive patients without PA, who exhibited enhanced ACTH‐dependent response of aldosterone secretion, underwent genetic testing for the presence of the CYP11B1/CYP11B2 chimeric gene and KCNJ5 gene mutations. Genomic DNA was isolated from peripheral white blood cells, and the exons of the entire coding regions of the above genes were amplified and sequenced. Electrophysiological studies were performed to determine the effect of identified mutation(s) on the membrane reversal potentials. Structural biology studies were also carried out.

Results

Two novel germline heterozygous KCNJ5 mutations, p.V259M and p.Y348N, were detected in the two subjects. Electrophysiological studies showed that the Y348N mutation resulted in significantly less negative reversal potentials, suggesting loss of ion selectivity, while the V259M mutation did not affect the Kir3.4 current. In the mutated structural biology model, the N348 mutant resulted in significant loss of the ability for hydrogen bonding, while the M259 mutant was capable of establishing weaker interactions. The CYP11B1/CYP11B2 chimeric gene was not detected.

Conclusions

These findings expand on the clinical spectrum of phenotypes associated with KCNJ5 mutations and implicate these mutations in the pathogenesis of hypertension associated with increased aldosterone response to ACTH stimulation.
Clinical characteristics of PRKACA mutations in Chinese patients with adrenal lesions: a single‐centre study
Authors: Li Xintao , Wang Baojun , Tang Lu , Lang Bin , Zhang Yu , Zhang Fan , Chen Luyao , Ouyang Jinzhi , Zhang Xu
Published: June 2016

Context

Recent studies have identified that the somatic PRKACA L206R mutation can cause cortisol‐producing adenomas (CPAs). This study investigated the prevalence and characteristics of PRKACA, GNAS and CTNNB1 mutations in adrenal lesions in patients from a single centre in China.

Design, Patients and Measurements

We sequenced PRKACA, GNAS and CTNNB1 genes in 108 patients, including 60 patients with CPAs (57 with unilateral and three with bilateral adenomas), 13 with nonfunctional adenomas, 12 with adrenocortical carcinomas (ACCs), 15 with primary bilateral macronodular hyperplasia (PBMAH) and eight with aldosterone and cortisol cosecreting adenomas. Mutations in PRKACA, GNAS and CTNNB1 were examined, and clinical characteristics were compared.

Results

Among the unilateral CPAs, we identified somatic mutations in PRKACA (L206R) in 23 cases (40·4%), GNAS (R201C and R201H) in six cases (10·5%), CTNNB1 (S45C, L46P and S45P) in six cases (10·5%) and CTNNB1 plus GNAS in two cases (3·5%). PRKACA and GNAS mutations were mutually exclusive. Among the patients with nonfunctional adenoma, two carried CTNNB1 mutations. Among the patients with ACC, two carried GNAS and CTNNB1 mutations but none carried PRKACA mutations. One patient showed bilateral CPA, and one PBMAH patient carried PRKACA mutations. No mutations in PRKACA, GNAS or CTNNB1 were identified in the eight patients with aldosterone and cortisol cosecreting adenomas. PRKACA‐mutant adenomas were associated with young age, overt Cushing's syndrome and high cortisol levels compared with non‐PRKACA‐mutant or CTNNB1‐mutant lesions.

Conclusions

PRKACA mutations are present in CPAs and bilateral adrenal macronodular hyperplasia. PRKACA mutation is associated with more severe autonomous cortisol secretion.
Hepatitis E in post‐liver transplantation: is it time to routinely consider it?
Authors: Borg Brian B. , Feng Zongdi , Earl Truman M. , Anderson Christopher D.
Published: June 2016

Hepatitis E, although commonly recognized in the Eastern Hemisphere, is less well recognized in the West. Particularly owing to this disease's grave impact on outcomes after liver transplantation, greater consideration of hepatitis E is necessary in the context of abnormal liver tests. Here, we review the most recent data on detecting and managing hepatitis E, both pre‐ and post‐liver transplantation, discuss major detection assay limitations, consider future directions, and propose an algorithm for the diagnosis and management of pre‐and post‐transplantation hepatitis E.
Impact and persistence of cirrhotic cardiomyopathy after liver transplantation
Authors: Sonny Abraham , Ibrahim Ahmed , Schuster Andres , Jaber Wael A. , Cywinski Jacek B.
Published: June 2016

Cirrhotic cardiomyopathy causes variable degree of systolic and diastolic dysfunction (DD) and conduction abnormalities. The primary aim of our study was to determine whether pre‐transplant DD and prolonged corrected QT (QTc) predict a composite of mortality, graft failure, and major cardiovascular events after liver transplantation. We also evaluated the reversibility of cirrhotic cardiomyopathy after transplantation. Adult patients who underwent liver transplantation at our institution from January 2007 to March 2009 were included. Data were obtained from institutional registry, medical record review, and evaluation of echocardiographic images. Among 243 patients, 113 (46.5%) had grade 1 DD, 16 (6.6%) had grade 2 DD, and none had grade 3 DD. The mean pre‐transplant QTc was 453 milliseconds. After a mean post‐transplant follow‐up of 5.2 years, 75 (31%) patients satisfied the primary composite outcome. Cox regression analysis did not show any significant association between DD and the composite outcome (P=.17). However, longer QTc was independently associated with the composite outcome (HR: 1.01, 95% confidence interval: 1.00–1.02, P=.05). DD (P<.001) and left ventricular mass index (P=.001) worsened after transplantation. In conclusion, QTc prolongation appears to be associated with worse outcomes. Although DD did not impact outcomes, it significantly worsened after transplantation.
Upper midline incision for living donor right hepatectomy
Authors: Singh Manoj K. , Lubezky Nir , Facciuto Matias , Contreras‐Saldivar Alan , Wadhera Vikram , Arvelakis Antonios , LaPointe‐Rudow Dianne , Florman Sander , Facciuto Marcelo E.
Published: June 2016

Background

Living donor liver transplantation is a viable option to increase access to transplantation and techniques to limit the operative incision is one way to increase donation by decreasing donor morbidity. We describe our experience with a limited upper midline incision (UMI) for living donor right hepatectomy.

Study Design

Prospective data were collected on 58 consecutive living liver donors who underwent right hepatectomy via a UMI.

Results

Donor median age was 32 years, with median body mass index of 24.6. The mean incision length was 11.7 cm. Ten liver grafts included middle hepatic vein. The mean graft volume by preoperative imaging was 940 cc. The mean operative time was 407 minutes; cellsaver was utilized in 35 patients with median of 1 unit. Mean peak aspartate transaminase (AST) and alanine transaminase (ALT) were 492 and 469, and peak bilirubin and international normalized ratio (INR) were 3.3 and 1.8. The average length of stay was 6 days. There were 10 Clavien grade I and 11 Clavien grade II complications. Three patients developed an incisional hernia requiring surgical repair.

Conclusion

Living liver donor hepatectomy can be safely performed through a UMI. This approach consolidates the steps of liver mobilization, hilar dissection, and parenchymal transection in a single‐exposure technique, with incision comparable to the laparoscopic‐assisted modality.
Training, work, and lifestyle of transplant physicians and surgeons in Germany
Authors: Hoyer Dieter P. , Kaiser Gernot M. , Cicinnati Vito , Radunz Sonia , Braun Felix , Greif‐Higer Gertrud , Schulze Maren , Schmidt Hartmut J. , Paul Andreas , Beckebaum Susanne
Published: June 2016

Background

International data on training, work, and lifestyle of transplant physicians and surgeons are scarce. Such data might help in development of uniform education paths and provide insights for young clinicians interested in this field. This study aimed at the evaluation of these data in all transplant‐associated medical disciplines.

Methods

A survey on professional and academic training, workload, and lifestyle was generated. The questionnaire was distributed to all members of the German Transplant Association (DTG), utilizing the tool SurveyMonkey®.

Results

A total of 127 members of the DTG responded (male/female 66.1%/33.9%, 45.8±10.3 years). The majority had been working in transplant medicine for more than 10 years (61.9%). Fifteen respondents (11.8%) obtained an official European certification (European Union of Medical Specialists). A total of 57 (48.3%) respondents worked full time on research during training. The research focus was clinical for most respondents (n=72, 61.5%). An average working time of 62±1.5 h/wk was reported. Fifty‐eight percent of all respondents complained of inadequate remuneration and 50% reported inadequate acknowledgment of their professional performance.

Conclusion

This is the first study reporting characteristics of training, work, and lifestyle in an interdisciplinary cohort of German transplant physicians and surgeons. Enormous efforts in clinical and research work were reported, associated with high rates of professional and financial dissatisfaction.
Development of the Assisting Hand Assessment for adolescents (Ad‐AHA) and validation of the AHA from 18 months to 18 years
Authors: Louwers Annoek , Beelen Anita , Holmefur Marie , Krumlinde‐Sundholm Lena
Published: June 2016

Aim

To develop and evaluate a test activity from which bimanual performance in adolescents with unilateral cerebral palsy (CP) can be observed and scored with the Assisting Hand Assessment (AHA), and to evaluate the construct validity of the AHA test items for the extended age range 18 months to 18 years.

Method

A new test activity was developed and evaluated for its ability to elicit bimanual actions in adolescents with (n=20) and without (n=10) unilateral CP. The AHA scores of 126 adolescents (mean age 14y 3mo, SD 2y 6mo; 71 males, 55 females) and 157 children with unilateral CP (mean age 6y 1mo, SD 2y 10mo; 102 males, 55 females) were analysed using the Rasch measurement model.

Results

The test activity elicited bimanual actions in 100% of typically developing adolescents and in 96.8% and 57.9% of adolescents with unilateral CP (moderately and severely limited hand function respectively). The scale demonstrated good construct validity; thus the same scoring criteria can be used for the age range studied.

Interpretation

The new Assisting Hand Assessment for adolescents (Ad‐AHA) activity is valid for use with 13‐ to 18‐year‐olds to elicit bimanual performance in adolescents with unilateral CP. The same AHA scoring criteria can be used both for children and for adolescents within the age range 18 months to 18 years.
CONSUMPTION EXTERNALITIES AND MONETARY POLICY WITH LIMITED ASSET MARKET PARTICIPATION
Authors: Airaudo Marco , Bossi Luca
Published: June 2016

This article explores the interaction between consumption externalities and limited asset market participation (LAMP) in the standard New‐Keynesian model. We assess the performance of simple Taylor‐type interest rate rules with respect to (a) equilibrium determinacy, (b) the model's ability to simultaneously generate output and inflation volatility similar to the pre‐Volcker era, and (c) the model's response to a technology shock. We find that when individual preferences are affected by average household consumption (Aggregate Consumption Externality), stronger externalities increase the range of LAMP for which multiple equilibria arise even if the policy rule satisfies the Taylor principle. The interaction of LAMP and externalities can generate vast inflation/output relative volatility in line with the one observed in the data in the 1970s. According to our analysis, consumption externalities also affect the responses of endogenous variables to total factor productivity shocks. (JEL E4, E5)
Is there a correlation between abundance and environmental suitability derived from ecological niche modelling? A meta‐analysis
Authors: Weber Marcelo M. , Stevens Richard D. , Diniz‐Filho José Alexandre F. , Grelle Carlos Eduardo V.
Published: June 2016

It is thought that species abundance is correlated with environmental suitability and that environmental variables, scale, and type of model fitting can confound this relationship. We performed a meta‐analysis to 1) test whether species abundance is positively correlated with environmental suitability derived from correlative ecological niche models (ENM), 2) test whether studies encompassing large areas within a species range (> 50%) exhibited higher AS correlations than studies encompassing small areas within a species range (< 50%), 3) assess which modelling method provided higher AS correlation, and 4) compare strength of the AS relationship between studies using only climatic variables and those that used both climatic and other environmental variables to derive suitability. We used correlation coefficients to measure the relationship between abundance and environmental suitability derived from ENM. Each correlation coefficient was considered an effect size in a random‐effects multivariate meta‐analysis. In all cases we found a significantly positive relationship between abundance and suitability. This relationship was consistent regardless of scale of study, ENM method, or set of variables used to derive suitability. There was no difference in strength of correlation between studies focusing on large or small areas within a species’ range or among ENM methods. Studies using other variables in combination with climate exhibited higher AS correlations than studies using only climatic variables. We conclude that occurrence data can be a reasonable proxy for abundance, especially for vertebrates, and the use of local variables increases the strength of the AS relationship. Use of ENMs can significantly decrease survey costs and allow the study of large‐scale abundance patterns using less information. Including only climatic variables in ENM may confound the relationship between abundance and suitability when compared to studies including variables taken locally. However, modelers and conservationists must be aware that high environmental suitability does not always indicate high abundance.
Subclinical temporal EEG seizure pattern in LGI1‐antibody–mediated encephalitis
Authors: Steriade Claude , Mirsattari Seyed M. , Murray Brian J. , Wennberg Richard
Published: June 2016

Leucine‐rich glioma inactived‐1 (LGI1) antibodies are associated with limbic encephalitis and distinctive seizure types, which are typically immunotherapy‐responsive. Although nonspecific electroencephalography (EEG) abnormalities are commonly seen, specific EEG characteristics are not currently understood to be useful for suspecting the clinical diagnosis. Based on initial observations in two patients, we analyzed the clinical features and EEG recordings in a larger series of patients (n = 9) and describe a novel ictal pattern that can suggest the diagnosis of LGI1‐antibody–mediated encephalitis, even in the absence of typical clinical features. As expected, psychiatric and cognitive symptoms were common, as were tonic seizures associated with EEG electrodecremental events (often with the so‐called faciobrachial dystonic semiology). Remarkably, in five patients, a near absence of interictal epileptiform discharges contrasted with frequent subclinical temporal lobe seizures, at times triggered by hyperventilation. This latter EEG pattern may facilitate early diagnosis of this serious but potentially treatable condition.
Letter to the Editor: Equine Veterinary Journal's antimicrobial stewardship policy
Authors: Bowen M. , Marr C.M. , Clegg P.D.
Published: June 2016

See correspondence by Hughes and Jago et al. and article by Jago et al.
Prospects and challenges of CRISPR/Cas genome editing for the study and control of neglected vector‐borne nematode diseases
Authors: Zamanian Mostafa , Andersen Erik C.
Published: June 2016

Neglected tropical diseases caused by parasitic nematodes inflict an immense health and socioeconomic burden throughout much of the developing world. Current estimates indicate that more than two billion people are infected with nematodes, resulting in the loss of 14 million disability‐adjusted life years per annum. Although these parasites cause significant mortality, they primarily cause chronic morbidity through a wide range of severe clinical ailments. Treatment options for nematode infections are restricted to a small number of anthelmintic drugs, and the rapid expansion of anthelmintic mass drug administration raises concerns of drug resistance. Preservation of existing drugs is necessary, as well as the development of new treatment options and methods of control. We focus this review on how the democratization of CRISPR/Cas9 genome editing technology can be enlisted to improve our understanding of the biology of nematode parasites and our ability to treat the infections they cause. We will first explore how this robust method of genome manipulation can be used to newly exploit the powerful model nematode Caenorhabditis elegans for parasitology research. We will then discuss potential avenues to develop CRISPR/Cas9 editing protocols in filarial nematodes. Lastly, we will propose potential ways in which CRISPR/Cas9 can be used to engineer gene drives that target the transmission of mosquito‐borne filarial nematodes.
Calibration and validation of optical chlorophyll‐measuring devices for use in predicting crude protein concentration in tropical grass herbage
Authors: Hughes M. P. , Lallo C. H. O. , Mlambo V. , Jennings P. G. A.
Published: June 2016

The objective of this experiment was to evaluate the Fieldscout CM 1000 NDVI and Yara N‐Tester as easy‐to‐use and cost‐effective tools for predicting foliar chlorophylls (a, b and total) and crude protein (CP) concentrations in herbage from three tropical grass species. Optical chlorophyll measurements were taken at three stages (4, 8 and 12 weeks) of regrowth maturity in Guinea grass (Panicum maximum) and Mulato II (Brachiaria hybrid) and at 6 and 12 weeks maturity in Paspalum spp (Paspalum atratum). Grass samples were harvested subsequent to optical measurements for laboratory analysis to determine CP and solvent‐extractable chlorophylls (a, b and total) concentrations. Optical chlorophyll measurements and CP concentrations were highly correlated (Yara N‐Tester: r2 = 0·77–0·89; Fieldscout CM 1000 NDVI: r2 = 0·52–0·84). Crude protein prediction models from the Yara N‐Tester and Fieldscout CM 1000 NDVI accounted for 70–89% and 44–73% CP variability, respectively, in Mulato II and Guinea grass. The Yara N‐tester produced more accurate and reliable CP estimates based on very high concordance correlation coefficient [CCC (0·73–0·91)] and low rMSPE, mean and regression bias. It is concluded that the Yara N‐Tester produces more accurate and reliable CP estimates of tropical pastures.
Biomass yield and nutrient content of a tropical mulberry forage bank: effects of season, harvest frequency and fertilization rate
Authors: González‐García E. , Martín Martín G.
Published: June 2016

Effects of season (SEAS), organic fertilization with laying hen manure (N) and harvest frequency (FREQ) on forage yield and composition were evaluated in a high‐density mulberry forage bank, established under low‐input tropical farming conditions. The experiment, replicated over two consecutive years, was arranged in 18 treatments resulting from a 3 × 3×2 factorial design which combined three FREQ (60, 90 and 120 d), 3 N rates (100, 300 and 500 kg N ha−1 year−1) and the two seasons (RAIN and DRY). Forage yield, leaf‐to‐stem ratio, the edible fraction (EDIB, %), nutrient content and the maturity indexes were monitored. Either forage yield or qualities by plant fraction were strongly affected by SEAS, FREQ, N rate and by their interactions. Effects of FREQ and N were modulated by SEAS. Increasing FREQ during RAIN negatively affected EDIB yield and quality after 90 d, while increasing ligneous fraction. During DRY, longer FREQ allowed higher total forage and EDIB yields. Leaves were more abundant in RAIN, and its yield was increased with fertilization but only during this season. Maturity indexes were higher in DRY than in RAIN. Under the conditions of this experiment, harvesting at 60 and 90 d in RAIN and DRY, respectively, with an N rate of 300 kg N ha−1 year−1 seems the best agronomic choice for an optimal compromise between forage yield and nutritive value.
Impact of Accessibility and Knowledge Creation on Local and Regional Development in Turkey
Authors: Ersoy Aksel
Published: June 2016

One of the fundamental aspects of the economic and social viability of the local and regional areas of Turkey is the degree to which they have access to the wider national economic and social system. Accessibility is, therefore, of major social, economic and political significance in Turkey and it directly affects Turkey's regional growth and the quality of life in local communities. However, the importance of the economic and social viability of the communities is increasingly complicated in the face of rapid global economic recession. It is argued that countries need to develop knowledge economies to compete successfully as knowledge is a critical factor for growth. This paper integrates accessibility and the importance of knowledge creation in understanding local and regional economic development. This empirical study has shown that although there is a high correlation between the accessibility index and the population figures of Turkey, accessibility to knowledge differs across Turkish provinces.
Honey bees: the queens of mass media, despite minority rule among insect pollinators
Authors: Smith Tobias J. , Saunders Manu E.
Published: June 2016

Pollination is a critical ecosystem function with high ecological and economic value. Conservation initiatives aimed at protecting diverse pollinator communities in natural and agricultural habitats are essential, but the implementation and success of such initiatives often depends on public support.

Mass media play an important role in building public awareness around environmental issues, and biased coverage can have damaging effects. Here, we present the first analysis of how Australian mainstream media present the ‘pollinator’ paradigm. We gathered insect pollinator and pollination related articles from major Australian online newspapers published over a period of 9 years, and performed a qualitative content analysis using deductive coding to record information on the pollinator species or groups discussed in the story.

We found 151 stories, and demonstrate that within these, there was a disproportionate focus on introduced European honey bees as the most important, or only, pollinator insect relevant to Australia. Only 15% of stories mentioned native bees as pollinators and 17% mentioned non‐bee pollinators.

There is potential that the trend we report here for pollinators may be indicative of a larger overall simplification and neglect of biodiversity concepts in mainstream media, both in Australia and globally. As public awareness of science and environmental issues partly depend on disseminating accurate information beyond the scholar network, it is imperative that the broader effects of inaccurate science communication are fully understood.
New toothpaste to deal with dentine hypersensitivity: double‐blind randomized controlled clinical trial
Authors: Katanec T , Majstorovic M , Negovetic Vranic D , Ivic Kardum M , Marks LA
Published: June 2016

Objectives

The purpose was to evaluate a combined effect of active ingredients contained in new toothpaste in reducing dentine hypersensitivity.

Methods

The tested toothpaste contained active ingredients potassium nitrate (5.00%) and zinc citrate (0.50%). Pain to water stimulus and blowing air was reported on hypersensitive teeth and measured using the VAS (Visual Analogue Scale). The degree of pain to water stimulus was detected after each subject drank a few sips of water which was boiled to the room temperature. Data were collected on each subject's dental history.

Results

A significant reduction in dentine hypersensitivity (26–29% after 2 weeks versus 40% after 4 weeks) was detected in the tested group. The controls also showed significant reduction to both stimuli, but at lower rate. A statistically significant difference to blowing air and water stimuli showed the highest impact for the tested group after 4 weeks (P = 0.033, P = 0.006).

Conclusion

This study supports the efficacy of the tested toothpaste in reducing the phenomenon of dentine hypersensitivity after 4 weeks of usage.