bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystal structure of 6-bromo-7-fluoro-4-oxo-4H-chromene-3-carbaldehyde
Authors: Ishikawa Yoshinobu
Published: June 2015

In the title compound, C10H4BrFO3, a brominated and fluorinated 3-formylchromone derivative, all atoms are essentially coplanar (r.m.s. deviation of 0.025 Å for the non-H atoms), with the largest deviation from the least-squares plane [0.050 (6) Å] being for a benzene-ring C atom. In the crystal, molecules are linked through stacking interactions [centroid–centroid distance between the benzene and pyran rings = 3.912 (4) Å], C—H...O hydrogen bonds and short C...O contacts [2.865 (7) Å]. Unsymmetrical halogen...halogen interactions between the bromine and fluorine atoms [Br...F = 3.116 (4) Å, C—Br...F = 151.8 (2), C—F...Br = 154.1 (4)°] are also formed, giving a meandering two-dimensional network propagating in the (041) plane. A comparison with related structures is made and the various types of weak interactions are ranked in importance.
Crystal structure of 3-bromo-2-hydroxybenzonitrile
Authors: Dickinson Sean R. , Müller Peter , Tanski Joseph M.
Published: June 2015

The crystal structure of the title compound, C7H4BrNO, has been determined, revealing a partial molecular packing disorder such that a 180° rotation of the molecule about the phenol C—O bond results in disorder of the bromine and nitrile groups. The disorder has been parameterized as a disorder of only the bromine and nitrile substituents on a unique phenol ring. An intramolecular O—H...Br contact occurs. In the crystal, O—H...Br/O—H...Nnitrilehydrogen bonding is present between the disordered bromine and nitrile substituents and the phenol group, forming a spiral chain about a twofold screw axis extending parallel to theb-axis direction. Within this spiral chain, the molecules also interact, forming offset face-to-face π-stacking interactions with plane-to-centroid distance of 3.487 (1) Å.
Crystal structure of 11-[4-(hexyloxy)phenyl]-1,2,4-triazolo[4,3-a][1,10]phenanthroline
Authors: Preis Jasmin , Schollmeyer Dieter , Detert Heiner
Published: June 2015

The title compound, C25H24N4O, was prepared from 2-chlorophenanthroline and hexyloxyphenyltetrazole. The main difference between the two independent molecules (AandB) in the asymmetric unit is the orientation of the all-anti-configured hexyloxy chain: inAthe C—O—C—C torsion angle is 175.9 (2)° whereas it is −88.3 (3)° inB. The benzene substitution in the bay of the triazolophenanthroline results in a helical distorsion of the heterocyclic core, the dihedral angles between the mean planes formed by quinoline and benzotriazole ring systems are 13.73 (9) for moleculeAand 14.87 (8)° for B. The dihedral angles between the triazole ring and the attached benzene ring are 45.87 (15) inAand 53.93 (14)° inB. The angular annulation of four rings and the benzene substituent results in a helical distortion of the aromatic framework. The crystal is formed from layers composed of centrosymmetric pairs ofA2,B2molecules with interdigitating alkyl chains.
Service experiences and dyadic value co-creation in healthcare service delivery: a CIT approach
Authors: Osei-Frimpong Kofi , Wilson Alan , Owusu-Frimpong Nana
Published: June 2015

Purpose

– The purpose of this paper is to investigate value co-creation processes from the focal dyad of the patient and the physician and how their experiences in the consulting room affect the value that is created.

Design/methodology/approach

– Semi-structured interviews incorporating the critical incident technique (CIT) were conducted with 8 doctors and 24 outpatients in selected hospitals in Ghana, exploring their experiences during their encounter in the service delivery impacting on the value creating healthcare opportunities. An abductive and thematic analytical approach was used to identify 76 useable critical incidents that had clear consequences on both the outcome of the service and the service experiences of the patient.

Findings

– The study reveals three critical areas needed to support the value co-creation process and respective elements or activities to be considered during the service encounter. The critical areas comprise of the social context, beliefs and perceptions, and partnership between the focal dyad. The findings also suggests that patients do not consider “getting well” as the only value that they seek, but also the total experiences they go through in the consulting room. Also some physicians find it difficult to accept the recent changes in the patients’ behaviour and attitudes, resulting in knowledge conflict that adversely affects actors’ experiences in the consulting room.

Research limitations/implications

– The study considered only one of the many professionals in the healthcare delivery, which may affect the true value perceptions of the patient.

Practical implications

– The study provides service providers understanding of the processes that influence the patients’ experiences and value creation and the changing trends in the patient’s attitudes. The findings suggest a need for providers to take a holistic view of the service delivery and consider the critical areas, which could impact on the overall service outcomes.

Originality/value

– This study extends the research on CIT to exploring the value co-creating processes in the healthcare setting. This also provides clarity in understanding the interdependence of the two actors and how this is managed as a resource in the value co-creation process at the micro level.
Physical and functional interaction between hepatitis C virus NS5A protein and ovarian tumor protein deubiquitinase 7B
Authors: Sianipar Imelda Rosalyn , Matsui Chieko , Minami Nanae , Gan Xiang , Deng Lin , Hotta Hak , Shoji Ikuo
Published: June 2015

Hepatitis C virus (HCV) NS5A protein plays crucial roles in viral RNA replication, virus assembly, and viral pathogenesis. Although NS5A has no known enzymatic activity, it modulates various cellular pathways through interaction with cellular proteins. HCV NS5A (and other HCV proteins) are reportedly degraded through the ubiquitin–proteasome pathway; however, the physiological roles of ubiquitylation and deubiquitylation in HCV infection are largely unknown. To elucidate the role of deubiquitylation in HCV infection, an attempt was made to identify a deubiquitinase (DUB) that can interact with NS5A protein. An ovarian tumor protein (OTU), deubiquitinase 7B (OTUD7B), was identified as a novel NS5A‐binding protein. Co‐immunoprecipitation analyses showed that NS5A interacts with OTUD7B in both Huh‐7 and HCV RNA replicon cells. Immunofluorescence staining revealed that HCV NS5A protein colocalizes with OTUD7B in the cytoplasm. Moreover, HCV infection was found to enhance the nuclear localization of OTUD7B. The OTUD7B‐binding domain on NS5A was mapped using a series of NS5A deletion mutants. The present findings suggest that the domain I of NS5A is important and the region from amino acid 121 to 126 of NS5A essential for the interaction. Either V121A or V124A mutation in NS5A disrupts the NS5A‐OTUD7B interaction. The results of this in vivo ubiquitylation assay suggest that HCV NS5A enhances OTUD7B DUB activity. Taken together, these results suggest that HCV NS5A protein interacts with OTUD7B, thereby modulating its DUB activity.
Persistent natural infection of a Culex tritaeniorhynchus cell line with a novel Culex tritaeniorhynchus rhabdovirus strain
Authors: Gillich Nadine , Kuwata Ryusei , Isawa Haruhiko , Horie Masayuki
Published: June 2015

Culex tritaeniorhynchus rhabdovirus (CTRV) is a mosquito virus that establishes persistent infection without any obvious cell death. Therefore, occult infection by CTRV can be present in mosquito cell lines. In this study, it is shown that NIID‐CTR cells, which were derived from Cx. tritaeniorhynchus, are persistently infected with a novel strain of CTRV. Complete genome sequencing of the infecting strain revealed that it is genetically similar but distinct from the previously isolated CTRV strain, excluding the possibility of contamination. These findings raise the importance of further CTRV studies, such as screening of CTRV in other mosquito cell lines.
Circulating irisin levels are associated with lipid and uric acid metabolism in a Chinese population
Authors: Tang Shanshan , Zhang Rong , Jiang Feng , Wang Jie , Chen Miao , Peng Danfeng , Yan Jing , Wang Shiyun , Bao Yuqian , Hu Cheng , Jia Weiping
Published: June 2015

Irisin is a novel hormone secreted by skeletal muscle after exercise, which may ameliorate insulin resistance. In this study, we aimed to explore the relationship between circulating irisin levels and type 2 diabetes mellitus (T2DM) as well as related metabolic traits in a Chinese population. A total of 203 subjects were recruited. Of these, 68 subjects with normal glucose tolerance (NGT), 63 subjects with impaired glucose regulation (IGR) and 72 subjects with new‐onset T2DM. Circulating irisin levels were measured by enzyme‐linked immunosorbent assay (ELISA). Detailed clinical investigations and biochemistry measurements were carried out in all of the subjects. Multivariate linear regression analysis was performed to assess the association between irisin levels and related metabolic characteristics. All subjects were classified into normal weight and overweight/obese subgroups according to body mass index (BMI). No significant differences in circulating irisin levels were identified among the three groups (P = 0.9741). After adjusting for covariates, multiple linear regression analysis revealed that serum irisin level was independently and significantly associated with total cholesterol (P = 0.0005), low‐density lipoprotein cholesterol (P = 0.0014), fasting fatty acids (P = 0.0402) and uric acid (P = 0.0062). By dividing the serum irisin levels into three tertile groups, the values of total cholesterol, low‐density lipoprotein cholesterol, fasting fatty acids and uric acid were all increased significantly with the increase of irisin (P < 0.05). Moreover, serum irisin levels remain closely related to total cholesterol in both normal weight and overweight/obese subgroups. Our study suggests that circulating irisin concentrations are significantly associated with lipid and uric acid metabolism in a Chinese population.
Hyperbaric oxygen pre‐treatment impairs anoxic tolerance but improves hyperglycemic tolerance in peripheral nerve
Authors: Stecker Mark M , Stevenson Matthew
Published: June 2015

Prior research has suggested that treatment with hyperbaric oxygen (HBO) may change energy metabolism in the peripheral nerve, potentially resulting in improved tolerance to hyperglycemia and anoxia. In this paper, the in vitro rat sciatic nerve model was used to explore the effects of a single 90 min treatment with either 1 or 3 atmospheres of: oxygen, nitrogen or air on the ability of the peripheral nerve to tolerate intermittent anoxia or hyperglycemia. After this treatment, the nerve was placed in a perfusion system where the nerve action potential (NAP) was continuously recorded over the duration of a 16 h experiment. The amplitude, paired pulse response, velocity and duration of the NAP were used as markers of peripheral nerve function. The perfusate contained either 5 mmol/L or 55 mmol/L glucose and was either continuously oxygenated or intermittently replaced by an oxygen free solution of identical composition. HBO treatment primarily affected the amplitude and duration of the NAP. HBO improved the NAP in continuously oxygenated nerves exposed to the 55 mmol/L glucose perfusate but not the 5 mmol/L. However, it worsened the NAP in nerves exposed to intermittent anoxia and increased the rate at which the amplitude of the NAP declined during anoxia. Pressure had an effect on the NAP only for oxygen but not nitrogen or air. The effect of the HBO treatment persisted more than 1 h after the end of the treatment.
Reproductive biology of Pachira aquatica Aubl. (Malvaceae: Bombacoideae): a tropical tree pollinated by bats, sphingid moths and honey bees
Authors: Hernández‐Montero Jesús R. , Sosa Vinicio J.
Published: June 2015

We investigated the reproductive biology, including the floral biology, pollination biology, breeding system and reproductive success, of Pachira aquatica, a native and dominant tropical tree of fresh water wetlands, throughout the coastal plain of the Gulf of Mexico. The flowers present nocturnal anthesis, copious nectar production and sugar concentration (range 18–23%) suitable for nocturnal visitors such as bats and sphingid moths. The main nocturnal visitors were bats and sphingid moths while bees were the main diurnal visitors. There were no differences in legitimate visitation rates among bats, moths and honey bees. Bats and honey bees fed mainly on pollen while moths fed on nectar, suggesting resource partitioning. Eight species of bats carried pollen but Leptonycteris yerbabuenae is probably the most effective pollinator due to its higher pollen loads. The sphingid moths Manduca rustica, Cocytius duponchel and Eumorpha satellitia were recorded visiting flowers. Hand pollination experiments indicated a predominant outcrossing breeding system. Open pollination experiments resulted in a null fruit set, indicating pollen limitation; however, mean reproductive success, according to a seasonal census, was 17 ± 3%; these contrasting results could be explained by the seasonal availability of pollinators. We conclude that P. aquatica is an outcrossing species with a pollination system originally specialized for bats and sphingid moths, which could be driven to a multimodal pollination system due to the introduction of honey bees to tropical America.
Leadership of Mayors and Governors during Crises: A Systematic Review on Tasks and Effectiveness
Authors: Jong Wouter , Dückers Michel L. A. , van der Velden Peter G.
Published: June 2015

The aim of this article is to provide a systematic review of peer‐reviewed literature on leadership tasks and effectiveness of mayors and governors during drastic collective events. A total of 34 peer‐reviewed articles met our criteria. They were analysed using the theoretical framework by Boin on leadership tasks, i.e., sense making, decision making, meaning making, terminating, and learning. Studies ranged from minor incidents like local riots, to the events of 9/11 and Hurricane Katrina. The material turned out to be dominated by Western and American studies. Because of limitations in the empirical and knowledge base of the studies, it is difficult to draw general conclusions on what is supposed to be effective leadership by mayors and/or governors in these circumstances.
Comparison of different methods of monitoring the secondary stage of oxidation of ghee
Authors: Mehta Bhavbhuti M , Aparnathi Kishorkumar D , Darji Vijaykumar B
Published: June 2015

Thiobarbituric acid value (TBA), ρ‐anisidine value (ρ‐AnV) and carbonyl value (CV) were compared with sensory scores in monitoring the oxidation of ghee. The latter used a 9‐point hedonic scale for flavour. Six samples of ghee were stored at 80 °C and samples were removed at 48‐h intervals. Correlation coefficients of the chemical values with flavour scores were CV −0.664, TBA −0.521 and p‐AnV −0.356, suggesting that the CV was the most suitable of the methods tested.
Systematic approach to study temperature and time effects on yield of pasta filata cheese
Authors: Bähler Balz , Ruf Thomas , Samudrala Ravi , Schenkel Philipp , Hinrichs Jörg
Published: June 2015

A batch cooker‐stretcher for pasta filata cheese production was developed based on the kitchen machine ‘Thermomix’. With this batch model system, the effect of kneading time (180, 420 and 600 s) and temperature (55, 60 and 70 °C) on the chemical composition of the pasta filata cheese and the yield was investigated. An increase in temperature from 55 to 70 °C reduced the yield of the pasta filata cheese production from 0.88 to 0.59 g/g, compared to initial curd weight. A correlation between process temperature and the water‐holding properties of protein (casein micelles) is proposed.
Invasive therapies for primary postpartum haemorrhage: a population‐based study in France
Authors: Kayem G , Dupont C , Bouvier‐Colle MH , Rudigoz RC , Deneux‐Tharaux C
Published: June 2015

Objective

To describe the characteristics, management, and outcomes of women undergoing invasive therapies for primary postpartum haemorrhage (PPH).

Design

A population‐based observational study.

Setting

All 106 maternity units of six French regions.

Population

A total of 146 781 women delivering between 2004 and 2006.

Methods

Prospective identification of women with PPH managed with invasive therapies, including uterine suture, pelvic vessel ligation, arterial embolisation, and hysterectomy.

Main outcome measures

Rate of use and failure rate of invasive therapies, with 95% confidence intervals (95% CIs).

Results

An invasive therapy was used in 296 of 6660 women with PPH (4.4%, 95% CI 4.0–5.0), and in 0.2% of deliveries (95% CI 0.18–0.23). A hysterectomy was performed in 72/6660 women with PPH (1.1%, 95% CI 0.8–1.4%), and in 0.05% of deliveries (95% CI 0.04–0.06). A conservative invasive therapy was used in 262 women, including 183 (70%) who underwent arterial embolisation and 79 (30%) who had conservative surgery as the first‐line therapy. Embolisation was more frequently used after vaginal than caesarean delivery, and when arterial embolisation was available on site. The failure rate of conservative invasive therapies was 41/262 (15.6%, 95% CI 11.5–20.6) overall, and was higher after surgical than after embolisation procedures, in particular for vaginal deliveries.

Conclusions

Both maternal mortality as a result of obstetric haemorrhage and the rate of invasive therapies used for PPH are high in France. These findings suggest flaws in the initial management of PPH and/or the inadequate use of invasive procedures.

Tweetable abstract

Maternal mortality as a result of haemorrhage and the rate of invasive therapies used for PPH are high in France.
Methods of classification for women undergoing induction of labour: a systematic review and novel classification system
Authors: Nippita TA , Khambalia AZ , Seeho SK , Trevena JA , Patterson JA , Ford JB , Morris JM , Roberts CL
Published: June 2015

Background

A lack of reproducible methods for classifying women having an induction of labour (IOL) has led to controversies regarding IOL and related maternal and perinatal health outcomes.

Objectives

To evaluate articles that classify IOL and to develop a novel IOL classification system.

Search strategy

Electronic searches using CINAHL, EMBASE, WEB of KNOWLEDGE, and reference lists.

Selection criteria

Two reviewers independently assessed studies that classified women having an IOL.

Data collection and analysis

For the systematic review, data were extracted on study characteristics, quality, and results. Pre‐specified criteria were used for evaluation. A multidisciplinary collaboration developed a new classification system using a clinically logical model and stakeholder feedback, demonstrating applicability in a population cohort of 909 702 maternities in New South Wales, Australia, over the period 2002–2011.

Main results

All seven studies included in the systematic review categorised women according to the presence or absence of varying medical indications for IOL. Evaluation identified uncertainties or deficiencies across all studies, related to the criteria of total inclusivity, reproducibility, clinical utility, implementability, and data availability. A classification system of ten groups was developed based on parity, previous caesarean, gestational age, number, and presentation of the fetus. Nulliparous and parous women at full term were the largest groups (21.2 and 24.5%, respectively), and accounted for the highest proportion of all IOL (20.7 and 21.5%, respectively).

Author's conclusions

Current methods of classifying women undertaking IOL based on medical indications are inadequate. We propose a classification system that has the attributes of simplicity and clarity, uses information that is readily and reliably collected, and enables the standard characterisation of populations of women having an IOL across and within jurisdictions.

Tweetable abstract

Methods classifying pregnant women having IOL are inadequate; we suggest a new classification system
Use of a high‐sensitivity troponin T assay in the assessment and disposition of patients attending a tertiary Australian emergency department: A cross‐sectional pilot study
Authors: Saad Yousef ME , McEwan James , Shugman Ibrahim M , Mussap Christian , Juergens Craig P , Ferguson Ian , French John K
Published: June 2015

Objective

We examined the disposition and outcomes of patients presenting to the ED with symptoms suggestive of acute coronary syndrome undergoing measurement of troponin T using a highly sensitive assay.

Methods

Troponin T (TnT) was measured in 204 consecutive patients (mean age = 65 [±18] years, 55% men) presenting to the ED with symptoms suggestive of acute coronary syndrome.

Results

Ninety‐four patients predominantly had chest pain, 34 had dyspnoea and the remainder had various symptoms. Overall, 96 patients had TnT >14 ng/L (upper reference limit), of whom 31 were admitted to the cardiology service (26 had final cardiac diagnosis [five ST‐elevation MI, 10 non‐ST‐elevation MI, one unstable angina and 10 other cardiac]). Among these 96 patients, 41 had chronic kidney disease, 17 had heart failure and seven had sepsis. At 30 days, death rates among patients who had TnT >14 ng/L with non‐cardiac diagnoses and in patients who had TnT >14 ng/L with a cardiac diagnosis were 6.6% and 2.9% (P = 0.652); no death and/or MI occurred in patients with normal TnT levels. At late follow up (median 6.8 months) that was obtained in 189 (93% of 204) patients, four had MI and 14 died (three cardiac deaths).

Conclusions

Despite high‐sensitivity TnT assay having a high sensitivity and specificity for myocardial necrosis, the majority of unselected consecutive patients attending ED in whom TnT levels were elevated did not have an acute coronary syndrome. Our pilot study suggests that a larger study is needed to provide evidence to modify management algorithms.
Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging
Authors: Ben‐Meir Assaf , Burstein Eliezer , Borrego‐Alvarez Aluet , Chong Jasmine , Wong Ellen , Yavorska Tetyana , Naranian Taline , Chi Maggie , Wang Ying , Bentov Yaakov , Alexis Jennifer , Meriano James , Sung Hoon‐Ki , Gasser David L. , Moley Kelle H. , Hekimi Siegfried , Casper Robert F. , Jurisicova Andrea
Published: June 2015

Female reproductive capacity declines dramatically in the fourth decade of life as a result of an age‐related decrease in oocyte quality and quantity. The primary causes of reproductive aging and the molecular factors responsible for decreased oocyte quality remain elusive. Here, we show that aging of the female germ line is accompanied by mitochondrial dysfunction associated with decreased oxidative phosphorylation and reduced Adenosine tri‐phosphate (ATP) level. Diminished expression of the enzymes responsible for CoQ production, Pdss2 and Coq6, was observed in oocytes of older females in both mouse and human. The age‐related decline in oocyte quality and quantity could be reversed by the administration of CoQ10. Oocyte‐specific disruption of Pdss2 recapitulated many of the mitochondrial and reproductive phenotypes observed in the old females including reduced ATP production and increased meiotic spindle abnormalities, resulting in infertility. Ovarian reserve in the oocyte‐specific Pdss2‐deficient animals was diminished, leading to premature ovarian failure which could be prevented by maternal dietary administration of CoQ10. We conclude that impaired mitochondrial performance created by suboptimal CoQ10 availability can drive age‐associated oocyte deficits causing infertility.
Relationship between prolactin, breast cancer risk, and antipsychotics in patients with schizophrenia: a critical review
Authors: De Hert M. , Peuskens J. , Sabbe T. , Mitchell A. J. , Stubbs B. , Neven P. , Wildiers H. , Detraux J.
Published: June 2015

Objective

A recent meta‐analysis showed that breast cancer probably is more common in female patients with schizophrenia than in the general population (effect size = 1.25, P < 0.05). Increasing experimental and epidemiological data have alerted researchers to the influence of prolactin (PRL) in mammary carcinogenesis. We therefore investigated the possible relationship between antipsychotic‐induced hyperprolactinemia (HPRL) and breast cancer risk in female patients with schizophrenia.

Method

A literature search (1950 until January 2015), using the MEDLINE database, was conducted for English‐language published clinical trials to identify and synthesize data of the current state of knowledge concerning breast cancer risk (factors) in women with schizophrenia and its (their) relationship between HPRL and antipsychotic medication.

Results

Although an increasing body of evidence supports the involvement of PRL in breast carcinogenesis, results of human prospective studies are limited, equivocal, and correlative (with risk ratios ranging from 0.70 to 1.9 for premenopausal women and from 0.76 to 2.03 for postmenopausal women). Moreover, these studies equally do not take into account the local production of PRL in breast epithelium, although amplification or overexpression of the local autocrine/paracrine PRL loop may be a more important mechanism in tumorigenesis. Until now, there is also no conclusive evidence that antipsychotic medication can increase the risk of breast malignancy and mortality.

Conclusion

Other breast risk factors than PRL, such as nulliparity, obesity, diabetes mellitus, and unhealthy lifestyle behaviours (alcohol dependence, smoking, low physical activity), probably are of greater relevance in individual breast cancer cases within the population of female patients with schizophrenia.
Population pharmacokinetics of infliximab in patients with inflammatory bowel disease: potential implications for dosing in clinical practice
Authors: Buurman D. J. , Maurer J. M. , Keizer R. J. , Kosterink J. G. W. , Dijkstra G.
Published: June 2015

Background

Infliximab (IFX) is effective in the treatment of inflammatory bowel diseases (IBD). Currently, IFX is administered at fixed doses and intervals; however, costs are high and optimisation is necessary. Several publications indicate that IFX should be dosed on trough levels ≥3.0 mg/L. For optimising IFX dosing, the use of a pharmacokinetic model is important. Population pharmacokinetics of IFX have been described earlier; however, these models were not used for dose optimising.

Aims

To develop a pharmacokinetic model for IFX in IBD patients that can be used for dose‐optimisation of IFX and to predict serum trough levels in this population.

Methods

An observational retrospective study was performed in 42 IFX‐treated IBD patients. Serum samples were drawn before infusion at T = 0, 2, 6, 14, 22 and 54 weeks and analysed for IFX and antibodies against IFX (ATI). Relevant covariates were recorded and a population pharmacokinetic model was developed.

Results

Individual plots created using the final model showed good correspondence between observed and model predicted values. Serum levels were influenced by ATI, disease activity, sex and albumin. Our results show that in patients without ATI target trough levels ≥3.0 mg/L can be achieved by increasing dosing intervals from 8 to 12 weeks combined with a dose increase. This results in a reduction of 33% in concomitant costs.

Conclusions

In IBD patients without ATI, trough level dosing based on longer intervals can reduce IFX therapy‐related visits to the hospital with one‐third. Trough level based dose intensification should always be justified by disease activity parameters.
Progressive decline in tacrolimus clearance after renal transplantation is partially explained by decreasing CYP3A4 activity and increasing haematocrit
Authors: de Jonge Hylke , Vanhove Thomas , de Loor Henriëtte , Verbeke Kristin , Kuypers Dirk R. J.
Published: June 2015

Aims

The long‐term disposition of tacrolimus following kidney transplantation is characterized by a gradual decrease in dose requirements and increase in dose‐corrected exposure. This phenomenon has been attributed to a progressive decline in cytochrome P450 3A4 (CYP3A4) activity, although this has never been demonstrated in vivo.

Methods

Sixty‐five tacrolimus‐ and 10 cyclosporine‐treated renal transplant recipients underwent pharmacokinetic testing at day 7 and months 1, 3, 6 and 12 after transplantation, including 8‐h area under the concentration‐time curve (AUC) for tacrolimus or cyclosporine and assessment of CYP3A4 activity using oral and intravenous midazolam (MDZ) drug probes.

Results

Tacrolimus clearance decreased gradually throughout the entire first year but only in CYP3A5*3/*3 homozygous recipients (25.6 ± 11.1 l h–1 at day 7; 17 ± 9.1 l h–1 at month 12; P < 0.001). In mixed model analysis, decreasing CYP3A4 activity, measured by apparent oral MDZ clearance (924 ± 443 ml min–1 at day 7 vs. 730 ± 344 ml min–1 at month 1; P < 0.001), explained 55.4% of the decline in tacrolimus clearance in the first month. CYP3A4 activity decreased by 18.9 ml min–1 for every milligram of methylprednisolone dose tapering within the first month; beyond this point it remained stable. A gradual rise in haematocrit throughout the entire first year explained 31.7% of the decrease in tacrolimus clearance in the first month and 23.6% of the decrease between months 1 and 12. Cyclosporine clearance did not change over time.

Conclusions

The maturation of tacrolimus disposition in the first year after renal transplantation observed in CYP3A5*3/*3 homozygous patients can partly be explained by a (steroid tapering‐related) decline in CYP3A4 activity and a progressive increase in haematocrit.
Autologous stem cell transplantation outcomes in elderly patients with B cell Non‐Hodgkin Lymphoma
Authors: Gohil Satyen H. , Ardeshna Kirit M. , Lambert Jonathan M. , Pule Martin A. , Mohamedbhai Sajir , Virchis Andres , Morris Emma C. , Linch David C. , Thomson Kirsty J. , Peggs Karl S.
Published: June 2015

The precise role of autologous haematopoietic stem cell transplantation (ASCT) remains unclear in patients over 60 years of age. There is potential for increased procedural morbidity and mortality, and differences in disease biology that could impact outcomes. We performed a retrospective single‐centre review of 81 elderly B‐cell Non‐Hodgkin Lymphoma patients undergoing ASCT. Five‐year overall survival (OS) and progression‐free survival (PFS) was 54·7% and 49·1% respectively. Non‐relapse mortality (NRM) at 100 days and 1 year was 1·3% and 2·5%, suggesting no major excess compared to younger cohorts. OS and PFS were significantly worse in those over 65 years compared to those aged 60–64 (47·6% vs. 57·7%, P = 0·0437, and 27·6% vs. 57·7%, P = 0·0052 at 5 years). This resulted largely from an increased relapse risk (RR) (53·8% vs. 30·1%, P = 0·0511) rather than excess NRM, and age remained independently significant for PFS on multivariate analyses [Hazard ratio 2·56 (1·35–4·84, P = 0·0052) for PFS and 1·89 (0·99–3·61, P = 0·054) for OS]. Our data adds to the growing body of evidence demonstrating that ASCT can be an effective treatment strategy with an acceptable safety profile in selected elderly patients. Further evaluation of its overall benefit is warranted, however, in those over 65 years of age, as RR appears to be considerably higher.
The association between parental imprisonment and the mental health of Palestinian adolescents
Authors: Shehadeh Amer , Loots Gerrit , Vanderfaeillie Johan , Derluyn Ilse
Published: June 2015

Background

Since 1967, the Palestinian Occupied Territories are marked by a protracted political conflict. During this conflict, about one fifth of the Palestinian population has been detained; a considerable part of them having children outside prison. Although parental detention negatively impacts children's psychological well‐being, little is known about this impact within contexts of protracted armed conflict. Therefore, this study aimed at gaining insight into the impact of parental detention onto adolescents' psychological well‐being.

Method

Of 314 (11‐ to 18‐year old) Palestinian adolescents who took part, the fathers of 204 adolescents were detained in Israeli prisons. The adolescents completed two self‐report questionnaires: the UCLA‐PTSD‐Reaction Index, investigating symptoms of posttraumatic stress, and the Strengths and Difficulties Questionnaire, looking at overall psychological problems. Several hierarchical regression analyses investigated mental health differences between both the groups, and possible associations between sociodemographic characteristics and the witnessing of the father's arrest, and the mental health outcomes.

Results

Parental detention largely impacted adolescents' mental health, with one fifth to two thirds of the adolescents reporting considerable mental health problems. Witnessing the arrest of the father even increased this risk considerably. Above, girls, younger adolescents, participants living in refugee camps, and those living with extended families also reported higher scores on both questionnaires.

Conclusions

Detention of fathers in the context of protracted armed conflicts has a large impact on adolescents' mental health. Besides an overall plea to end armed conflicts as fast as possible, the study also delineates considerable implications for the support and care for these adolescents and their families.
Combination of humans, climate, and vegetation change triggered Late Quaternary megafauna extinction in the Última Esperanza region, southern Patagonia, Chile
Authors: Villavicencio Natalia A. , Lindsey Emily L. , Martin Fabiana M. , Borrero Luis A. , Moreno Patricio I. , Marshall Charles R. , Barnosky Anthony D.
Published: June 2015

South America lost around 52 genera of mammals during a worldwide event known as the Late Quaternary Extinction episode. More than 80% of South American mammals weighing > 44 kg succumbed. Analysis of the megafaunal extinction chronology in relation to human arrival and major climate changes have revealed slightly different extinction patterns in different eco‐regions of the continent, highlighting the importance of detailed regional analysis in order to understand how the possible drivers of extinction operated. Here we present an analysis of the megafaunal extinction in the Última Esperanza (UE) area of southwestern Patagonia, Chile. We have compiled a comprehensive chronology of megafaunal extinctions and earliest human occupation between 18–7 cal ka BP, based on radiocarbon dates from published literature. We calculated confidence intervals using the GRIWM method to estimate the times of human arrival and megafaunal local extinctions, and then compared these events to the timing of major climate and vegetation changes, fire frequency increase, and the Reclús volcanic eruption. Our results suggest that a combination of human impacts and climate–vegetation change drove megafaunal extinctions in the UE area, with the balance of factors being taxon specific; the volcanic eruption does not seem to have exacerbated extinctions. Competition between humans and mega‐carnivores seems to be the most plausible cause for the extinction of the mega‐carnivores. Coexistence of humans with extinct horses, extinct camels, and mylodonts for several thousand years rules out a scenario of blitzkrieg overkill of megafauna by humans. The transition of vegetation from cold grasslands to Nothofagus forests corresponds with the disappearance of Hippidion saldiasi and Lama cf. owenii. The later full establishment of Nothofagus forests and an increasing fire frequency coincided with the disappearance of mylodonts. A climate‐driven reduction of open environments plausibly reduced herbivore's populations making them susceptible to local extinction.
Estimation of density threshold of gregarization of desert locust hoppers from field sampling in Mauritania
Authors: Cisse Sory , Ghaout Saïd , Mazih Ahmed , Ould Babah Ebbe Mohamed Abdallahi , Piou Cyril
Published: June 2015

For desert locusts, Schistocerca gregaria (Forskål) (Orthoptera: Acrididae), the hopper density threshold of gregarization remains poorly documented. Field sampling was carried out in traditional seasonal breeding areas of Mauritania during two successive years without invasion to approximate the gregarization threshold. Hopper densities were assessed at numerous sampling sites. Vegetation was also sampled to characterize the habitats. Hopper behavior was analyzed in situ with the help of a behavioral circular arena to test our assumptions on empirical locust phases determination based on physical appearance (coloration and behavior) following FAO guidelines. The results provided a critical density value around 2.45 hoppers m−2, above which gregarious hoppers were expected to be seen more frequently in nature. Hopper density was confirmed as the main factor explaining the presence of gregarious individuals. The level of involvement of vegetation parameters such as plant density, basal area, volume, distance between plants, greenness, or combinations of these indicators was low in explaining the observation of gregarious hoppers compared with hopper density. Vegetation cover and height were the only vegetation characteristics that could enhance the prediction of phase status with hopper density. The hoppers' phase determined from their behavior observed in the arena was similar to that characterized through FAO guidelines phase assessment, making consistent the field sampling method. Additionnally, the use of this arena illustrated that the grouping behavior of hoppers is a gradual response to density. This study can be seen as a step forward in the estimation of hopper density thresholds of gregarization in the field. This should improve the decision making for intervention during preventive control operations.
How much have we learned about seasonality in tropical insect abundance since Wolda (1988)?
Authors: Kishimoto‐Yamada Keiko , Itioka Takao
Published: June 2015

Seasonal patterns in climatic conditions affect the life cycles and temporal patterns in the abundance of most temperate insect species. In tropical regions where there is no winter season, the situation may be different. For a better understanding of the evolution of seasonal life cycles, and the dynamics affecting temporal patterns in abundance of tropical insect populations and assemblages, it is important to study the life cycles of tropical insects and the presence or absence of seasonality in relation to climatic conditions. By reviewing studies on temporal patterns of abundance, this article examines the patterns of seasonality in adult tropical forest insects and discusses the variation in such patterns in various forest types. Seasonal and aseasonal patterns were found to be common in tropical dry and wet regions, respectively. In wet regions, which lack a distinctive dry season, there exists a wide variety of temporal patterns in addition to aseasonal patterns: distinctively seasonal and supra‐annual fluctuations in some insect species. Some of the problems of hidden ecological mechanisms underlying seasonal patterns in abundance are discussed, and the definition of seasonality in temporal patterns of insect abundance at a particular stage in the life cycle is considered. Methodological problems are also discussed.
Genetic improvement for important farmed aquaculture species with a reference to carp, tilapia and prawns in Asia: achievements, lessons and challenges
Authors: Nguyen Nguyen Hong
Published: June 2015

This study provides an overview of successful genetic improvement programmes for important farmed aquaculture species in Asia, with a focus on lessons and experiences gained as well as challenges remaining. In both fish and prawns (Macrobrachium rosenbergii), conventional selective breeding approaches have resulted in significant improvement in productivity, with genetic gains ranging from 8 to 12% per generation. Selection for high growth has also brought about beneficial changes in fillet weight of fish and edible meat in prawns without detrimental effects on flesh quality attributes and fitness‐related traits. Genetically improved animals show remarkable vigour and high adaptation to a range of culture environments/conditions in Asian countries. Despite these successes, however, the conduct and practical implementation of such breeding programmes still present several challenges. These include the expansion of breeding objectives, management of inbreeding in closed‐selection populations, controlling the effects of genotype by environment interactions, simultaneous production of large number of full‐ and half‐sib families for species with asynchronous spawning behaviour, maintaining pedigree records, dissemination of the improved strains for widespread production, as well as a reluctance by many to carry out systematically designed genetic improvement for aquatic animal species. There are also challenges with regard to the application of genomic information in genetic enhancement programmes and the development of genetically improved strains in response to climate and environmental changes. In this study, each of these challenges is discussed and solutions are proposed to increase efficiency of future genetic improvement programmes for economically important aquaculture species.
BDNF signaling in the rat cerebello‐vestibular pathway during vestibular compensation: BDNF signaling in vestibular compensation
Authors: Zhou Liuqing , Zhou Wen , Zhang Sulin , Liu Bo , Liang Pei , Zhou Yan , Zhou Tao , Zhang Kun , Leng Yangming , Kong Weijia
Published: June 2015

Vestibular compensation, which is the behavioral recovery from lesions to the peripheral vestibular system, is attributed to plasticity of the central vestibular system. It has been reported that brain‐derived neurotrophic factor (BDNF) is expressed and released in an activity‐dependent manner. Upon binding to the tyrosine receptor kinase B (TrkB), BDNF can acutely modulate synaptic transmission and plasticity in the central nervous system. To assess the possible contribution of BDNF to this recovery process, we studied the expression of BDNF, TrkB.FL, TrkB.T1 and KCC2 (K+‐Cl− cotransporter isoform 2) in the bilateral medial vestibular nucleus (MVN) and the flocculus of rats at 4 h, 8 h, 1, 3 and 7 days following unilateral labyrinthectomy (UL) using immunohistochemistry, quantitative real‐time PCR and western blotting. Our results have shown that, compared with the sham controls and the contra‐lesional side, (a) the expression of BDNF and TrkB.FL increased at 4 h in the ipsi‐lesional flocculus after UL; (b) the expression of TrkB.T1 decreased at 4 h and KCC2 decreased at 8 h and 1 day in the ipsi‐lesional flocculus after UL; and (c) BDNF and TrkB.FL expression was enhanced and KCC2 expression was reduced in the ipsi‐lesional MVN at 8 h after UL. Our data supported the hypothesis that BDNF upregulation may reduce the inhibitory effects of the flocculus and commissural inhibition system by regulating inhibitory GABAergic synaptic transmission in floccular Purkinje cells and Purkinje cell terminals in the MVN. Additionally, KCC2 may be a switch in this process.
Evaluation of downstream migration mitigation actions for eel at an Archimedes screw pump pumping station
Authors: Buysse D. , Mouton A. M. , Baeyens R. , Coeck J.
Published: June 2015

Eel, Anguilla anguilla (L.), mortality was studied in a Belgian lowland canal after downstream passage through a large and small de Wit‐adapted Archimedes screw pump over a 12‐month period. The hypothesis tested was the minimisation of fish injuries with the de Wit adaptation. Simultaneously, downstream migration through a Dutch pool and orifice fishway alongside the pumping station (PS) was monitored. Nets were mounted on the outflow of the pumps, and a cage was placed in the fishway. Based on the condition of the fish and injuries sustained, the assessed maximum mortality rates ranged from 19 ± 4% for the large de Wit Archimedes screw pump to 14 ± 8% for the small de Wit Archimedes screw pump. The screw adaptations did not substantially minimise grinding injuries and overall mortality, and the fishway did not mitigate downstream eel migration. To achieve escapement targets set in the eel management plans, fish‐friendly pump designs and effective PS bypass solutions are needed.
Island and island‐like marine environments
Authors: Dawson Michael N.
Published: June 2015

Islands are pieces of land entirely surrounded by sea on which terrestrial and marine organisms live as little as a few metres apart. Yet, in contrast to terrestrial species, marine species have attracted little attention in studies of island theory. The experimental and conceptual origins of this dichotomy date back to the 1970s, although the apposition has softened in the early 2000s, in part a consequence of phylogeographic analyses and the discovery of new marine environments. Here, I explore the possible range of island and island‐like settings in the marine realm and find good evidence, albeit in short supply, for integrating marine with terrestrial perspectives during the current transition from equilibrium to general dynamic models of island biogeography. This integration of marine systems into island theory will be facilitated by three advances: (1) development of many descriptive marine studies to reduce the current deficit, (2) design of rigorous comparative studies within and across realms, and (3) modification of conceptual models to unite seemingly disparate situations, for example describing islands in terms of ecological–evolutionary processes. Marine island biogeography is in its infancy; it may present situations that are uncommon in the existing literature, but not rare in nature, and thus contribute substantially to the new dynamic outlook on a half‐century‐old theme.
‘I'm a sick person, not a bad person’: patient experiences of treatments for alcohol use disorders
Authors: McCallum Stacey L , Mikocka‐Walus Antonina A , Gaughwin Matthew D , Andrews Jane M , Turnbull Deborah A
Published: June 2015

Background

Emerging research indicates that standard treatments for alcohol use disorders may not fully meet the needs of patients with co‐occurring severe mental health symptoms. Investigating health quality indicators may provide insight into how current treatment might be improved.

Objective

To better understand the experiences of patients receiving treatment for alcohol use disorders and compare the experiences of patients with and without co‐occurring severe mental health symptoms.

Design

Cross‐sectional qualitative research design using semi‐structured interviews methods and framework analysis approach.

Setting

Inpatient hospital, outpatient service, inpatient detoxification clinic and a residential/ therapeutic community.

Participant's

Thirty‐four patients receiving treatment for an alcohol use disorder.

Main variables studied

Themes relating to patients' experiences of continuity of care, treatment need and satisfaction with treatment were studied. The qualitative data were divided into two groups: patients with (n = 15) and without (n = 19) severe mental health symptoms.

Results

Five themes relating to patient satisfaction with treatment were identified, including: perceived effectiveness of treatment, supportive relationships, specialized but holistic care, patient autonomy and continuity of care. A diverse range of patient treatment needs, staff and service continuity and stigma were also identified as major themes. Five basic themes were identified as more critical to the experiences of patients with severe mental health symptoms.

Discussion and conclusions

Findings suggest that patients look for supportive relationships with others, to be involved in treatment decisions, effective specialized and holistic approaches to care and a non‐judgemental treatment environment.