bluuebunny/crossref_metadata_2025 huggingface dataset:
Industrial Policy in Response to the Middle‐income Trap and the Third Wave of the Digital Revolution
Authors: Wade Robert H
Published: September 2016

The ‘middle‐income trap’ (MIT) is ‘real enough’ for policy makers in developing countries to take it as a serious threat to prospects for achieving ‘high’ average income. Those prospects are further clouded by the major changes occurring as the digital revolution moves from connecting people to the internet to connecting the internet to everything else, across many sectors of human life (the Third Wave). Both sets of forces raise the potential advantages of pro‐active industrial policy. Yet mainstream economic thinking – and the consensus of international development organizations like the World Bank – has long tended to disapprove of it, in the spirit of ‘The best industrial policy is none at all’. In light of the middle‐income trap, the Third Wave, and other conditions in the world economy, this essay discusses some of the big issues in the design of industrial policy, on the theme of how to do it well rather than how to do it less.
Combining Varenicline (Chantix) with Naltrexone Decreases Alcohol Drinking More Effectively Than Does Either Drug Alone in a Rodent Model of Alcoholism
Authors: Froehlich Janice C. , Fischer Stephen M. , Dilley Julian E. , Nicholson Emily R. , Smith Teal N. , Filosa Nick J. , Rademacher Logan C.
Published: September 2016

Background

This study examined whether varenicline (VAR), or naltrexone (NTX), alone or in combination, reduces alcohol drinking in alcohol‐preferring (P) rats with a genetic predisposition toward high voluntary alcohol intake.

Methods

Alcohol‐experienced P rats that had been drinking alcohol (15% v/v) for 2 h/d for 4 weeks were fed either vehicle (VEH), VAR alone (0.5, 1.0, or 2.0 mg/kg body weight [BW]), NTX alone (10.0, 15.0, or 20.0 mg/kg BW), or VAR + NTX in 1 of 4 dose combinations (0.5 VAR + 10.0 NTX, 0.5 VAR + 15.0 NTX, 1.0 VAR + 10.0 NTX, or 1.0 VAR + 15.0 NTX) at 1 hour prior to alcohol access for 10 consecutive days, and the effects on alcohol intake were assessed.

Results

When administered alone, VAR in doses of 0.5 or 1.0 mg/kg BW did not alter alcohol intake but a dose of 2.0 mg/kg BW decreased alcohol intake. This effect disappeared when drug treatment was terminated. NTX in doses of 10.0 and 15.0 mg/kg BW did not alter alcohol intake but a dose of 20.0 mg/kg BW decreased alcohol intake. Combining low doses of VAR and NTX into a single medication reduced alcohol intake as well as did high doses of each drug alone. Reduced alcohol intake occurred immediately after onset of treatment with the combined medication and continued throughout prolonged treatment.

Conclusions

Low doses of VAR and NTX, when combined in a single medication, reduce alcohol intake in a rodent model of alcoholism. This approach has the advantage of reducing potential side effects associated with each drug. Lowering the dose of NTX and VAR in a combined treatment approach that maintains efficacy while reducing the incidence of negative side effects may increase patient compliance and improve clinical outcomes for alcoholics and heavy drinkers who want to reduce their alcohol intake.
Creatine Supplementation Does Not Prevent the Development of Alcoholic Steatosis
Authors: Ganesan Murali , Feng Dan , Barton Ryan W. , Thomes Paul G. , McVicker Benita L. , Tuma Dean J. , Osna Natalia A. , Kharbanda Kusum K.
Published: September 2016

Background

Alcohol‐induced reduction in the hepatocellular S‐adenosylmethionine (SAM):S‐adenosylhomocysteine (SAH) ratio impairs the activities of many SAM‐dependent methyltransferases. These impairments ultimately lead to the generation of several hallmark features of alcoholic liver injury including steatosis. Guanidinoacetate methyltransferase (GAMT) is an important enzyme that catalyzes the final reaction in the creatine biosynthetic process. The liver is a major site for creatine synthesis which places a substantial methylation burden on this organ as GAMT‐mediated reactions consume as much as 40% of all the SAM‐derived methyl groups. We hypothesized that dietary creatine supplementation could potentially spare SAM, preserve the hepatocellular SAM:SAH ratio, and thereby prevent the development of alcoholic steatosis and other consequences of impaired methylation reactions.

Methods

For these studies, male Wistar rats were pair‐fed the Lieber‐DeCarli control or ethanol (EtOH) diet with or without 1% creatine supplementation. At the end of 4 to 5 weeks of feeding, relevant biochemical and histological analyses were performed.

Results

We observed that creatine supplementation neither prevented alcoholic steatosis nor attenuated the alcohol‐induced impairments in proteasome activity. The lower hepatocellular SAM:SAH ratio seen in the EtOH‐fed rats was also not normalized or SAM levels spared when these rats were fed the creatine‐supplemented EtOH diet. However, a >10‐fold increased level of creatine was observed in the liver, serum, and hearts of rats fed the creatine‐supplemented diets.

Conclusions

Overall, dietary creatine supplementation did not prevent alcoholic liver injury despite its known efficacy in preventing high‐fat‐diet‐induced steatosis. Betaine, a promethylating agent that maintains the hepatocellular SAM:SAH, still remains our best option for treating alcoholic steatosis.
Challenging the definition of the subfamily Usiinae: Phthiraxini, an unusual new tribe of bee flies (Diptera: Bombyliidae), based on Phthiraxia bowdeni gen. and sp. nov. from Western Australia
Authors: Li Xuankun , Yeates David K
Published: September 2016

A new genus Phthiraxia gen. nov. (Usiinae: Phthiriini) is described from a remote region of Western Australia based on a male and a female specimen collected 35 years ago. The pair represent a single new species Phthiraxia bowdeni sp. nov. Two important characteristics of this new genus, however, challenge the definition of the subfamily Usiinae: the clypeus does not reach the base of antennae, and the palp is two‐segmented. Moreover, Phthiraxia gen. nov. has two other features: the wing vein M2 present, shared by all members of Phthiriini, and flagellum with subapical shallow sulcus containing a style, differentiating it from Phthiriini with a deep apical sulcus, and Usiini with a deep subapical sulcus. Results of a morphological phylogenetic analysis show that the new genus belongs to a lineage that is sister to the remaining members of the subfamily. Therefore, a monotypic new tribe, Phthiraxini tribus nov., is described to accommodate Phthiraxia gen. nov. A key to the Australian genera of Usiinae is provided. We reevaluate the syapomorphies of the Usiinae in light of the new tribe.
National cross‐sectional study of nonsteroidal anti‐inflammatory drugs use highlights differences between parents and professionals and prompts safety concerns
Authors: Bertille Nathalie , Pons Gérard , Fournier‐Charrière Elisabeth , Khoshnood Babak , Chalumeau Martin
Published: September 2016

Aim

Controversy surrounding the safety of nonsteroidal anti‐inflammatory drugs (NSAIDs) provides an opportunity to study parents’ and healthcare professionals’ differential use of over‐the‐counter drugs.

Methods

In this national cross‐sectional study, general practitioners, paediatricians and pharmacists were asked to include up to five consecutive febrile paediatric patients aged 1 month to 12 years. Parents and healthcare professionals completed questionnaires about the current fever episode. We studied the differential use of NSAIDs by parents and healthcare professionals notably in three clinical conditions with various estimated risk of NSAIDs complications: varicella, gastroenteritis and pharyngitis.

Results

The 1534 healthcare professionals prescribed 15% of the 6596 children with an NSAID, but 32% of the parents gave their child an NSAID. Generally, NSAID use was associated with older children, higher temperatures, pain due to otitis and the absence of a rash or gastroenteritis. The differential use of NSAIDs by parents and professionals was greater in conditions with high than low estimated risks of NSAID complications, with odds ratios ranging from to 9.0 to 2.9, respectively.

Conclusion

The differential use of NSAIDs by healthcare professionals and parents for clinical conditions with potential risks should prompt discussions about the safety of their over‐the‐counter status.
Dietary carbohydrate intake, insulin resistance and gastro‐oesophageal reflux disease: a pilot study in European‐ and African‐American obese women
Authors: Pointer S. D. , Rickstrew J. , Slaughter J. C. , Vaezi M. F. , Silver H. J.
Published: September 2016

Background

Although obesity rates are higher in African‐American than European‐American women, gastro‐oesophageal reflux disease (GERD) and its comorbidities are more prevalent in European‐American women. A common denominator for increased adiposity, and consequent insulin resistance, is excess dietary macronutrient intake – which may promote greater prevalence and severity of GERD in women.

Aim

To investigate whether GERD is more robustly associated with dietary carbohydrate intake, particularly dietary simple carbohydrate intake, and insulin resistance in European‐American women.

Methods

About 144 obese women were assessed at baseline and 16 weeks after consuming a high‐fat/low‐carbohydrate diet. GERD diagnosis and medication usage was confirmed in medical records with symptoms and medications assessed weekly.

Results

About 33.3% (N = 33) of European‐American and 20.0% (N = 9) of African‐American women had GERD at baseline. Total carbohydrate (r = 0.34, P < 0.001), sugars (r = 0.30, P = 0.005), glycaemic load (r = 0.34, P = 0.001) and HOMAIR (r = 0.30, P = 0.004) were associated with GERD, but only in European‐American women. In response to high‐fat/low‐carbohydrate diet, reduced intake of sugars was associated with reduced insulin resistance. By the end of diet week 10, all GERD symptoms and medication usage had resolved in all women.

Conclusions

GERD symptoms and medication usage was more prevalent in European‐American women, for whom the relationships between dietary carbohydrate intake, insulin resistance and GERD were most significant. Nevertheless, high‐fat/low‐carbohydrate diet benefited all women with regard to reducing GERD symptoms and frequency of medication use.
False Self‐Employment, Autonomy and Regulating for Decent Work: Improving Working Conditions in the UK Stripping Industry
Authors: Cruz Katie , Hardy Kate , Sanders Teela
Published: September 2016

A large‐scale study of working conditions in UK‐based strip dancing clubs reveals that dancers are against de facto self‐employment as it is defined and practised by management, but in favour of de jure self‐employment that ensures sufficient levels of autonomy and control in the workplace. While dancers could potentially seek ‘worker’ or ‘employee’ status within the existing legal framework, their strong identification with the label ‘self‐employed’ and their desire for autonomy will likely inhibit these labour rights claims. We propose an alternative avenue for improving dancers’ working conditions, whereby self‐employed dancers articulate their grievances as a demand for decent work, pursued through licensing agreements between clubs and local authorities and facilitated by collective organization.
FGFR gene alterations in lung squamous cell carcinoma are potential targets for the multikinase inhibitor nintedanib
Authors: Hibi Masaaki , Kaneda Hiroyasu , Tanizaki Junko , Sakai Kazuko , Togashi Yosuke , Terashima Masato , De Velasco Marco Antonio , Fujita Yoshihiko , Banno Eri , Nakamura Yu , Takeda Masayuki , Ito Akihiko , Mitsudomi Tetsuya , Nakagawa Kazuhiko , Okamoto Isamu , Nishio Kazuto
Published: September 2016

Fibroblast growth factor receptor (FGFR) gene alterations are relatively frequent in lung squamous cell carcinoma (LSCC) and are a potential targets for therapy with FGFR inhibitors. However, little is known regarding the clinicopathologic features associated with FGFR alterations. The angiokinase inhibitor nintedanib has shown promising activity in clinical trials for non‐small cell lung cancer. We have now applied next‐generation sequencing (NGS) to characterize FGFR alterations in LSCC patients as well as examined the antitumor activity of nintedanib in LSCC cell lines positive for FGFR1 copy number gain (CNG). The effects of nintedanib on the proliferation of and FGFR signaling in LSCC cell lines were examined in vitro, and its effects on tumor formation were examined in vivo. A total of 75 clinical LSCC specimens were screened for FGFR alterations by NGS. Nintedanib inhibited the proliferation of FGFR1 CNG‐positive LSCC cell lines in association with attenuation of the FGFR1–ERK signaling pathway in vitro and in vivo. FGFR1 CNG (10.7%), FGFR1 mutation (2.7%), FGFR2 mutation (2.7%), FGFR4 mutation (5.3%), and FGFR3 fusion (1.3%) were detected in LSCC specimens by NGS. Clinicopathologic features did not differ between LSCC patients positive or negative for FGFR alterations. However, among the 36 patients with disease recurrence after surgery, prognosis was significantly worse for those harboring FGFR alterations. Screening for FGFR alterations by NGS warrants further study as a means to identify patients with LSCC recurrence after surgery who might benefit from nintedanib therapy.
Is TSH necessary for initial assessment of thyroid nodules?
Authors: Cai Haidong , Qiao Yu , Xi Hao , Luo Qiong , Yuan Xueyu , Yang Yuehua , Lv Zhongwei
Published: September 2016

Objective

The use of thyrotropin (TSH) in the initial assessment of thyroid nodules is inefficient and leads to unnecessary assessment costs. We compared the total costs of thyroid nodule assessment with or without the use of TSH in the initial assessment.

Methods

A total of 1808 patients with thyroid nodules received TSH, fine‐needle aspiration (FNA) and thyroid scintigraphy (TS) assessment, including 83 autonomously functioning thyroid nodule (AFTN) cases and 1725 non‐AFTN cases. The total costs of the TSH strategy and non‐TSH strategies were compared. The ratio of single‐use costs of FNA to TS (CFNA/TS) was used as the main outcome measure.

Results

Only when 6·03 ≤ CFNA/TS ≤ 27·17, the lowest total costs were associated with using the conventional TSH strategy. When CFNA/TS <6·03 or CFNA/TS >27·17, the lowest costs were found with FNA and TS, respectively.

Conclusion

From the perspective of cost economics, in iodine‐sufficient areas, we recommend that the decision on the use of TSH for the initial assessment of thyroid nodules should be based on the testing costs of FNA and TS in that medical unit.
What do social workers and children do when they are together? A typology of direct work
Authors: Whincup Helen
Published: September 2016

There is renewed interest in the place of direct work and relationship‐based practice in social work. This paper explores the day‐to‐day direct work that happens where children and young people are ‘looked after’ at home, from the perspectives of children, social workers and those supervising practice. It is based on interviews with eight children and 25 professionals about their experiences. In this paper, I highlight that despite barriers, direct work, which is characterized as meaningful by children and professionals, happens and that the relationships formed between children and social workers are an important precursor to and an outcome of direct work. The research was undertaken in Scotland, and although the legislation, policy and guidance differ from other jurisdictions, the messages about direct work are relevant for practice in other countries.
Recognizing the tenascin‐X deficient type of Ehlers–Danlos syndrome: a cross‐sectional study in 17 patients
Authors: Demirdas S. , Dulfer E. , Robert L. , Kempers M. , van Beek D. , Micha D. , van Engelen B.G. , Hamel B. , Schalkwijk J. , Loeys B. , Maugeri A. , Voermans N.C.
Published: September 2016

The tenascin‐X (TNX) deficient type Ehlers–Danlos syndrome (EDS) is similar to the classical type of EDS. Because of the limited awareness among geneticists and the challenge of the molecular analysis of the TNXB gene, the TNX‐deficient type EDS is probably to be under diagnosed. We therefore performed an observational, cross‐sectional study. History and physical examination were performed. Results of serum TNX measurements were collected and mutation analysis was performed by a combination of next‐generation sequencing (NGS), Sanger sequencing and multiplex ligation‐dependent probe amplification (MLPA). Included were 17 patients of 11 families with autosomal recessive inheritance and childhood onset. All patients had hyperextensible skin without atrophic scarring. Hypermobility of the joints was observed in 16 of 17 patients. Deformities of the hands and feet were observed frequently. TNX serum level was tested and absent in 11 patients (seven families). Genetic testing was performed in all families; 12 different mutations were detected, most of which are suspected to lead to non‐sense mRNA mediated decay. In short, patients with the TNX‐deficient type EDS typically have generalized joint hypermobility, skin hyperextensibility and easy bruising. In contrast to the classical type, the inheritance pattern is autosomal recessive and atrophic scarring is absent. Molecular analysis of TNXB in a diagnostic setting is challenging.
The effect of experimental osteoporosis on bone regeneration: part 2, proteomics results
Authors: Calciolari E. , Mardas N. , Dereka X. , Anagnostopoulos A. K. , Tsangaris G. T. , Donos N.
Published: September 2016

Objectives

To identify and describe protein expression in a Wistar rat calvarial critical size defect (CSD) model following treatment with guided bone regeneration in healthy and osteoporotic conditions.

Material and methods

Thirty‐six 10‐month‐old female Wistar rats were used. Half of them were ovariectomized (OVX) and fed with a low‐calcium diet to induce an osteoporotic‐like status. In each animal of both groups, two 5‐mm calvarial CSDs were treated with deproteinized bovine bone mineral graft particles and a bilayer collagen membrane. Six OVX and six control rats were randomly euthanized at 7, 14, and 30 days. One defect/animal was randomly chosen for proteomic analysis. Differently expressed proteins between the two groups were identified with matrix‐assisted laser desorption time‐of‐flight mass spectrometry and liquid chromatography–mass spectrometry/mass spectrometry.

Results

At 7 days, 29 and 27 proteins were, respectively, identified in the healthy and OVX animals. At 14 days, 103 proteins were detected in the healthy controls and 20 proteins in the OVX rats, while at 30 days, 31 and 75 proteins were identified, respectively. Only limited proteins known to play a role in the later stages of bone formation and maturation were identified within the animals ‘proteomes.

Discussion

The osseous formation process was quite immature even at 30 days of healing. An overexpression of inflammatory and stress response pathways was detected in the OVX animals, as well as a tendency toward a delayed maturation of the osseous wound and a reduced/delayed differentiation of osteoblast cell precursors.
Recanalized umbilico‐caval anastomosis as a temporary portosystemic shunt in pediatric living donor liver transplantation: the crossed fingers method
Authors: Urahashi Taizen , Ihara Yoshiyuki , Sanada Yukihiro , Okada Noriki , Yamada Naoya , Hirata Yuta , Katano Takumi , Mizuta Koichi
Published: September 2016

A temporary portocaval shunt (TPCS) associated with retrohepatic vena cava preservation prevents the edema caused by splanchnic congestion during liver transplantation (LT), especially for non‐cirrhotic cases. We herein report a modified TPCS technique using the recanalized umbilical vein and an end‐to‐side recanalized umbilico‐caval anastomosis for use during pediatric living donor liver transplantation (LDLT). This work evaluated a group of pediatric patients who underwent LDLT between 2001 and 2014 with the conventional TPCS (n=16) vs the recanalized umbilico‐caval shunt (the crossed fingers method, n=10). The crossed fingers method was performed by suturing an end‐to‐side anastomosis of the patent or recanalized umbilical vein to the vena cava using a continuous monofilament suture like “crossing the fingers,” that is, placing the left portal vein across the portal vein trunk next to it. The preoperative, surgical, and postoperative characteristics were similar in both groups except for the significantly shorter portal vein clamping time for the crossed fingers method. This method can allow the portal circulation to be totally decompressed before and after implanting the graft and while maintaining the hemodynamic stability throughout all stages of pediatric LDLT.
Allograft biopsy findings in patients with small bowel transplantation
Authors: Koo Jamie , Dawson David W. , Dry Sarah , French Samuel W. , Naini Bita V. , Wang Hanlin L.
Published: September 2016

In this study, we sought to determine the incidence of post‐transplant complications including acute cellular rejection (ACR), infection, and post‐transplant lymphoproliferative disease (PTLD) in mucosal allograft biopsies in patients with small bowel transplant at our institution. We retrospectively reviewed pathology reports from 5675 small bowel allograft biopsies from 99 patients and analyzed the following: indications for biopsy, frequency and grade of ACR, the presence of infectious agents, results of workup for potential PTLD, results of C4d immunohistochemistry (IHC), features of chronic mucosal injury, and findings in concurrent native bowel biopsies. Findings from 42 allograft resection specimens were also correlated with prior biopsy findings. Indeterminate, mild, moderate, and severe ACR were seen in 276 (4.9%), 409 (7.2%), 100 (1.8%), and 207 (3.6%) of biopsies, respectively. Although ACR may show histologic overlap with mycophenolate mofetil toxicity, we found the analysis of concurrent native bowel biopsies to be helpful in this distinction. Adenovirus was the most common infectious agent seen (11%), and we routinely performed adenovirus IHC on biopsies. Eighteen patients (18%) developed PTLD, 83% of which were EBV associated, but only 28% of PTLD cases were diagnosed on mucosal allograft biopsies. C4d IHC did not correlate with the presence of donor‐specific antibodies in limited cases.
Attitudes toward organ donation among waitlisted transplant patients: results of a cross‐sectional survey
Authors: Merola Jonathan , Pei Kevin Y. , Rodriguez‐Davalos Manuel I. , Gan Geliang , Deng Yanhong , Mulligan David C. , Davis Kimberly A.
Published: September 2016

Organ shortage remains a major barrier to transplantation. While many efforts have focused on educating the general population regarding donation, few studies have examined knowledge regarding donation and donor registration rates among waitlisted candidates. We aimed to determine waitlisted patients' willingness to donate, elucidate attitudes surrounding organ allocation, and identify barriers to donation. A cross‐sectional survey was distributed to assess demographics, knowledge regarding organ donation, and attitudes regarding the allocation process. Responses from 225 of 579 (39%) waitlisted patients were collected. Seventy‐one respondents (32%) were registered donors, while 64 patients (28%) noted no interest in participating in donation. A total of 19% of respondents felt their medical treatment would change by being a donor, while 86 patients (38%) felt their condition precluded them from donation. Forty patients (18%) felt they should be prioritized on the waitlist if they agreed to donate. A minority of patients (28%) reported discussion of organ donation with their physician. Waitlisted candidates constitute a population of willing, although often unregistered, organ donors. Moreover, many endorse misconceptions regarding the allocation process and their donation eligibility. In a population for which transplantation is not always possible, education is needed regarding organ donation among waitlisted patients, as this may enhance donation rates.
Macroevolution of perfume signalling in orchid bees
Authors: Weber Marjorie G. , Mitko Lukasz , Eltz Thomas , Ramírez Santiago R.
Published: September 2016

Theory predicts that both stabilising selection and diversifying selection jointly contribute to the evolution of sexual signalling traits by (1) maintaining the integrity of communication signals within species and (2) promoting the diversification of traits among lineages. However, for many important signalling traits, little is known about whether these dynamics translate into predictable macroevolutionary signatures. Here, we test for macroevolutionary patterns consistent with sexual signalling theory in the perfume signals of neotropical orchid bees, a group well studied for their chemical sexual communication. Our results revealed both high species‐specificity and elevated rates of evolution in perfume signals compared to nonsignalling traits. Perfume complexity was correlated with the number of congeners in a species’ range, suggesting that perfume evolution may be tied to the remarkably high number of orchid bee species coexisting together in some neotropical communities. Finally, sister‐pair comparisons were consistent with both rapid divergence at speciation and character displacement upon secondary contact. Together, our results provide new insight into the macroevolution of sexual signalling in insects.
Retinal structure and function in vigabatrin‐treated adult patients with refractory complex partial seizures
Authors: Sergott Robert C. , Johnson Chris A. , Laxer Kenneth D. , Wechsler Robert T. , Cherny Katya , Whittle JoAnn , Feng Ge , Lee Deborah , Isojarvi Jouko
Published: September 2016

Objective

Evaluate visual‐field and retinal‐structure changes following adjunctive vigabatrin treatment in vigabatrin‐naive adults with refractory complex partial seizures (rCPS).

Methods

Prospective, longitudinal, single‐arm, open‐label study (NCT01278173). Eligible patients (≥2 seizures/month who failed ≥3 therapies) who could reliably perform perimetry (Humphrey automated static) and retinal‐structure assessment (spectral‐domain optical coherence tomography) prior to vigabatrin exposure. Following vigabatrin initiation, testing occurred within 1 month (reference) and 3, 6, 9, and 12 months. End points included mean change from reference in mean deviation (dB) and average retinal nerve fiber layer (RNFL) thickness, visual‐acuity changes from baseline, and number of patients who met predefined vision‐parameter changes at two (confirmed) or three (persistent) consecutive visits.

Results

Sixty‐five of 91 screened patients received ≥1 vigabatrin dose (all‐patients‐treated set [APTS]); 55 had valid reference and ≥1 post–reference assessments (full‐analysis set [FAS]). Thirty‐six APTS patients with valid pre–/post–reference values completed all planned visits (per‐protocol set [PPS]). Thirty‐eight (59%) APTS patients completed the study; 27 (42%) withdrew (none for visual‐field changes); 32% and 15% had abnormally thin RNFL and abnormal visual acuity at baseline, respectively; 20% had abnormal central 30 degree visual fields in the reference period. No significant mean near visual‐field changes were observed (PPS); mean change in average RNFL thickness increased significantly (1‐year data: Left‐eye: 6.37 μm, confidence interval (CI) 4.66–8.09; right‐eye: 7.24 μm CI 5.47–9.01; PPS). No confirmed three‐line decreases in visual acuity (FAS) were observed; five patients had predefined confirmed/persistent visual‐field changes (FAS). All vision‐related adverse events were nonserious; the most common was vision blurred (9%).

Significance

Prior to vigabatrin initiation, rCPS patients may already exhibit vision deficits. Up to 1 year of adjunctive vigabatrin treatment did not significantly change population near visual fields. Five patients met predefined visual‐field‐change criteria. RNFL thickening of unknown clinical significance was observed. Limitations include single‐arm, open‐label design; patients’ inability to perform ophthalmic/visual‐field examinations; and limited vigabatrin‐exposure duration.
Articular sagittal and medial parasagittal patellar fracture repair using lag screws in two mature horses
Authors: Vautravers G. , Brandenberger O. , Vitte A. , Rossignol F.
Published: September 2016

This report describes the clinical experience with internal fixation of a sagittal and a medial parasagittal patellar fracture using lag screws. Severely displaced sagittal and medial parasagittal fractures of the patella were diagnosed in 2 horses (a 10‐year‐old Thoroughbred gelding and a 5‐year‐old Thoroughbred mare) and were repaired using internal fixation. A direct approach through thefascia lataewas used. In both cases, the leg was placed in full extension and the fracture was corrected by a combination of digital manipulation and application of bone reduction forceps. Articular congruency was assured by arthrotomy and digital assessment, and radiographic skyline projection. Then, the leg was placed in flexion and two 5.5 mm cortical screws with washers were inserted in lag fashion, under radiographic guidance (skyline projection). In one case, an additional 6.5 mm cancellous screw was used. Both fractures healed without evidence of degenerative joint disease. However, the first horse's wound dehisced, then healed by second intention uneventfully. The second horse was put in a sling in order to prevent lying down. Both horses were able to be used for their intended purpose. In these clinical cases, sagittal and medial parasagittal patellar fractures were treated successfully by open reduction and internal fixation. Post‐operative management in a sling was used successfully in the second case to prevent wound dehiscence.
Which psychoactive substances are used by patients seen in the healthcare system in French overseas territories? Results of the OPPIDUM survey
Authors: Daveluy Amélie , Frauger Elisabeth , Peyrière Hélène , Moracchini Christophe , Haramburu Françoise , Micallef Joëlle
Published: September 2016

Addiction to illicit substances or medicines is influenced by cultural, religious, ethnic factors as well as local availability. The purpose of this study was to evaluate the profile of drug users and characteristics of the psychoactive substances used in French overseas territories, using data from the OPPIDUM survey. OPPIDUM is an annual, nationwide, multicentric, cross‐sectional study based on specialized care centres that included subjects presenting a drug addiction or under opiate maintenance treatment. The current study includes data from the 2012 and 2013 surveys and focuses on patients included by drug addiction centres located in French overseas departments and territories: French Pacific Ocean (French Polynesia, New Caledonia), French Americas (Guadeloupe, Saint Martin, French Guiana) and Reunion Island. Data from metropolitan France (2013 survey) were included as reference. Two hundred and forty‐five patients were included. The sex ratio was 3.7 for the Pacific Ocean, 3.5 for the French Americas and 3.3 for Reunion Island. Cannabis was consumed in all the territories, from 50.8% in Reunion Island to 81.7% in Pacific Ocean. Cocaine was most frequently consumed in the French Americas (61%), mainly in the ‘freebase’ form (91%), whereas 6.5% of cocaine users in metropolitan France did so. Problematic use of medicines was most frequent in Reunion Island. Heroin seems rarely used in all overseas territories. This study highlights the complexity of substances used in French overseas territories, which often differ from that in mainland France. The relative difference between different areas provides valuable information for future investigations and possible interventions.
Revealing the pathways by which agricultural land‐use affects stream fish communities in South Brazilian grasslands
Authors: Dala‐Corte Renato B. , Giam Xingli , Olden Julian D. , Becker Fernando G. , Guimarães Taís de F. , Melo Adriano S.
Published: September 2016

Understanding mechanisms by which agricultural practices affect freshwater ecosystems helps to inform land‐use policies and management strategies aimed at mitigating effects of agriculture on biodiversity. Land‐use activities in the catchment, riparian and local scales likely influence stream fish communities via multiple pathways, for instance, by modifying the instream habitat.

We investigated the mechanisms driving local stream fish taxonomic richness and functional diversity in South Brazilian grasslands by testing a theoretical path model in which we specified a priori relationships predicting how land use at multiple scales affects instream habitat and fish communities.

Agricultural activities adjacent to streams (i.e. local impact on the streambank) and catchment‐scale cropland area were positively related to macrophyte cover and negatively associated with coarse particulate organic matter (CPOM, i.e. woody debris and leaf litter). Local impact also increased substrate siltation and homogenisation. Riparian vegetation in the upstream buffer ameliorated instream habitat condition by dampening macrophyte proliferation and providing CPOM.

Fish species richness increased with both macrophyte cover and CPOM, revealing multiple pathways of agricultural influence. However, functional diversity decreased only with substrate siltation, revealing a response to agricultural activities adjacent to sample sites. Agricultural streams showed a replacement of benthic and lithophilic species by a larger number of morphologically similar and macrophyte‐associated nektonic fish.

Our study indicates that land‐use adjacent to streams and upstream riparian zones is critical for maintaining taxonomically and functionally diverse fish communities due to their strong effects on instream habitat. Protection and recovery of riparian zones from land‐use change can mitigate the effects of agriculture on fish communities in South Brazilian grasslands.
Lessons from the fish: a multi‐species analysis reveals common processes underlying similar species‐genetic diversity correlations
Authors: Fourtune Lisa , Paz‐Vinas Ivan , Loot Géraldine , Prunier Jérôme G. , Blanchet Simon
Published: September 2016

Species‐genetic diversity correlations (SGDCs) have been investigated over a large spectra of organisms, which has greatly improved our understanding of parallel processes potentially driving both species and genetic diversity. However, there are still few studies comparing SGDCs (and underlying processes) for multiple species sampled over a single landscape.

Here, focusing on freshwater fish sampled across a large river basin (the Garonne‐Dordogne river basin, France), we combined a multi‐species approach and causal analyses to (i) assess and compare both α‐SGDCs and β‐SGDCs among species, and (ii) infer processes underlying α‐SGDCs and β‐SGDCs. Genetic, intraspecific diversity was assessed for four sympatric fish (Barbatula barbatula, Gobio occitaniae, Phoxinus phoxinus and Squalius cephalus) using microsatellite markers. Species diversity was quantified as species richness using electric fishing, and environmental conditions were thoroughly described for 81 sites.

We found significant and moderate positive α‐SGDCs for all four fish species, whereas β‐SGDCs were weaker in strength and positively significant for two of the four species. Causal analyses identified two common variables (geographical isolation and area of available habitats) underlying the α‐SGDC relationships. Although weak, we found that β‐SGDC correlations related to a direct relationship between taxonomic and genomic differentiation, and to the common influence of the abiotic environment acting as a filter on both species and alleles.

Our study shows that similar ecological and evolutionary processes related to environmental filtering, migration, drift and colonisation history act for explaining both species and genetic diversity of fish communities.
Does Intelligence Affect Economic Diversification?
Authors: Kodila-Tedika Oasis , Asongu Simplice A.
Published: September 2016

This paper extends the growing literature on knowledge economy by investigating the effect of intelligence on economic diversification. Using a battery of estimation techniques that are robust to endogeneity, we find that human capital has positive correlations with export diversification, manufactured added value and export manufactures. This empirical evidence is based on a world sample of 170 countries for the year 2010. The findings have significant implications for the fight against the Dutch disease. In essence, investing in human capital could bring economic diversity and therefore dampen negative external shocks related to resource-dependence. Other knowledge-economy implications are discussed.
Comprehensive behavioral study and proteomic analyses of CRMP2‐deficient mice
Authors: Nakamura Haruko , Yamashita Naoya , Kimura Ayuko , Kimura Yayoi , Hirano Hisashi , Makihara Hiroko , Kawamoto Yuko , Jitsuki‐Takahashi Aoi , Yonezaki Kumiko , Takase Kenkichi , Miyazaki Tomoyuki , Nakamura Fumio , Tanaka Fumiaki , Goshima Yoshio
Published: September 2016

Collapsin response mediator protein 2 (CRMP2) plays a key role in axon guidance, dendritic morphogenesis and cell polarization. CRMP2 is implicated in various neurological and psychiatric disorders. However, in vivo functions of CRMP2 remain unknown. We generated CRMP2 gene‐deficient (crmp2−/−) mice and examined their behavioral phenotypes. During 24‐h home cage monitoring, the activity level during the dark phase of crmp2−/− mice was significantly higher than that of wild‐type (WT) mice. Moreover, the time during the open arm of an elevated plus maze was longer for crmp2−/− mice than for WT mice. The duration of social interaction was shorter for crmp2−/− mice than for WT mice. Crmp2−/− mice also showed mild impaired contextual learning. We then examined the methamphetamine‐induced behavioral change of crmp2−/− mice. Crmp2−/− mice showed increased methamphetamine‐induced ambulatory activity and serotonin release. Crmp2−/− mice also showed altered expression of proteins involved in GABAergic synapse, glutamatergic synapse and neurotrophin signaling pathways. In addition, SNAP25, RAB18, FABP5, ARF5 and LDHA, which are related genes to schizophrenia and methamphetamine sensitization, are also decreased in crmp2−/− mice. Our study implies that dysregulation of CRMP2 may be involved in pathophysiology of neuropsychiatric disorders.
Gender, the Body and Organization Studies: Que(e)rying Empirical Research
Authors: de Souza Eloisio Moulin , Brewis Jo , Rumens Nick
Published: September 2016

Even in organization studies scholarship that treats gender as performative and fluid, a certain ‘crystallization’ of gender identities as somehow unproblematic and stable may occur because of our methodological decision‐making, and especially our categorization of participants. Mobilizing queer theory — and Judith Butler's work on the heterosexual matrix and performativity in particular — as a conceptual lens, we examine this crystallization, suggesting it is based on two implicit assumptions: that gender is a cultural mark over a passive biological body, or is a base identity ‘layered over’ by other identities (class, race, age etc.). Following Butler, we argue that in order to foreground the fluidity and uncertainty of gender categories in our scholarship, it is necessary to understand gender identity as a process of doing and undoing gender that is located very precisely in time and space. Given this perspective on gender identities as complex processes of identification, non‐identification and performativity, we offer some pointers on how the methodological decision‐making underpinning empirical research on gender, work and organization could and should begin from this premise.
Recognizing the need for personalization of haemophilia patient‐reported outcomes in the prophylaxis era
Authors: Recht M. , Konkle B. A. , Jackson S. , Neufeld E. J. , Rockwood K. , Pipe S.
Published: September 2016

The safety and efficacy of treatment options for patients with haemophilia have significantly improved over the last two decades, particularly with greater utilization of prophylactic approaches. Consequently, it is becoming increasingly difficult to differentiate the treatment benefits of available choices based on standard endpoints such as annualized bleeding rates and joint health scores. Patient‐reported outcomes (PROs) have shown limited ability to discriminate between treatment outcomes, in part because of their comprehensive nature; i.e. differences in specific outcomes meaningful to individual patients are masked by a global scoring system based on a fixed set of items, many of which may be unimportant for any given patient. There is a clear need for new outcome measures. Initiatives to develop patient‐centric outcomes that capture clinically meaningful change are ongoing. One such approach, goal attainment scaling (GAS), allows patients, in collaboration with a trained clinician, to select goals from a medical condition‐specific menu of options and subsequently facilitates quantitative assessment of goal realization. Thus, it is fully personalized and sensitive to small, often idiosyncratic, treatment benefits, such as improvements in functional capacity. In this paper, we present the underlying rationale for GAS and one other novel approach to PRO personalization, and discuss their potential to augment current outcome measures by reliably detecting and quantifying treatment effects in individuals with haemophilia on prophylaxis.
HLA‐DQ gene polymorphisms are associated with hepatocellular carcinoma and hepatitis B surface antigen in chronic hepatitis B virus infection
Authors: Ochi Yuka , Hashimoto Senju , Kawabe Naoto , Murao Michihito , Nakano Takuji , Kan Toshiki , Nakaoka Kazunori , Ohki Masashi , Kurashita Takamitsu , Takamura Tomoki , Nomura Sayuri , Nishikawa Toru , Fukui Aiko , Osakabe Keisuke , Ichino Naohiro , Yoshioka Kentaro
Published: September 2016

Aim

Genome‐wide association studies have revealed that single nucleotide polymorphism (SNP) of human leukocyte antigen (HLA)‐DQ is associated with the clearance of hepatitis B surface antigen (HBsAg) in acute hepatitis B virus (HBV) infection. We examined the effects of SNPs on the development of hepatocellular carcinoma (HCC) and markers of HBV in chronic HBV infection.

Methods

The SNPs of HLA‐DQ (rs2856718 and rs7453920) were determined in 299 patients with chronic HBV infection.

Results

In 224 hepatitis B e antigen (HBeAg)‐negative patients, those with rs2856718 genotype AG + GG had significantly lower hepatitis B core‐related antigen levels (P = 0.0184), less frequent treatment with nucleotide/nucleoside analogs (NAs) (P = 0.0433), and less frequent HCC development (P = 0.0256) than those with genotype AA. Multivariate analysis selected age (P = 0.0460), platelet count (P = 0.0481), γ‐glutamyl transpeptidase (P = 0.0030), and nucleotide/nucleoside analog treatment (P = 0.0003) as factors independently associated with HCC development. HBeAg‐negative patients with rs7453920 genotype GG had significantly lower HBsAg levels (P < 0.0001), a higher prevalence of HBV genotype C (P = 0.0063), and a lower prevalence of the wild‐type basal core promoter region (P = 0.0045) than those with genotype AA + AG. Multivariate analysis selected age (P < 0.0001), platelet count (P = 0.0021), HBV DNA levels (P = 0.0314), wild type of precore region (P = 0.0015), and rs7453920 (P < 0.0001) as factors independently associated with HBsAg levels.

Conclusion

This study revealed an association between rs2856718 and HCC development and an association between rs7453920 and HBsAg levels.
Reversal of tubo‐ovarian atypical epithelial patterns after cessation of ovarian stimulation by letrozole
Authors: Abdel‐Hamid Ahmed A.M. , Mesbah Yaser , Soliman Mona F.M.
Published: September 2016

Letrozole (LTZ), one of the ovulation induction medications, is increasingly prescribed in various gynaecological conditions. Previous studies have demonstrated its potential hazardous effect on the ovarian surface epithelium (OSE) as well as on tubal epithelial cells (TEC). However, it is not clear whether this effect could be reversed by LTZ cessation. Therefore, the objective of our study was to investigate the effect of stoppage of LTZ on these cells after 12 cycles of ovarian stimulation. A total of 54 Sprague Dawley rats were used in this study, divided equally into control, LTZ12 and CES12 groups (received saline, 12 cycles of LTZ and 12 cycles of cessation post‐LTZ12 respectively). Samples from the ovaries as well as fallopian tubes (FTs) were studied histologically for the changes associated with LTZ12 and CES12 respectively. There was evident increase in the proliferative activity and Ki67 immunoexpression in the OSE of LTZ12. The OSE was hyperchromatic, and abnormally frequent deep invaginations, micropapillae and cortical cysts. Their TEC showed frequent multilayering, papillary projections and loss of cilia. Almost all these changes disappeared 12 cycles after LTZ cessation. While the tubal IL‐1β, IL‐6, TNF‐α and serum MCP‐1 levels significantly increased in the LTZ12 group compared with the control group, their levels decreased in the CES12 group compared with those of the control. Therefore, the abnormal tubo‐ovarian epithelial patterns may completely regress after cessation of LTZ stimulation for a reasonable duration. This is a potentially good omen and a positive indicator of the relatively safe use of LTZ after its intake has been stopped.
Fell‐Muir Lecture: Regulatory mechanisms of skeletal and connective tissue development and homeostasis – lessons from studies of human disorders
Authors: Olsen Bjorn R. , Berendsen Agnes D. , Besschetnova Tatiana Y. , Duan Xuchen , Hu Kai
Published: September 2016

Studies of proliferative hemangiomas have led to the discovery that interactions of endothelial cells with extracellular matrix and/or Vascular Endothelial Growth Factor (VEGF)‐A stimulate the expression of VEGFR1, the VEGF decoy receptor, and suppress VEGF‐dependent VEGFR2 signalling by a mechanism that requires the matrix‐binding receptor Anthrax Toxin Receptor (ANTXR)1, VEGFR2, β1 integrin and the Nuclear Factor of Activated T cells (NFAT). In hemangioma endothelial cells, all these components are present, but are functionally compromised, so that the levels of VEGFR1 are extremely low and VEGFR2 signalling is constitutively active. Consequently, the levels of Hypoxia Inducible Factor (HIF)‐1α and its transcriptional targets, VEGF‐A and C‐X‐C motif chemokine 12 (CxCl12), are elevated and a positive VEGF‐A feedback loop is established. Overexpression of ANTXR1, carrying a heterozygous Ala‐to‐Thr mutation, induces hemangioma‐like signalling in control endothelial cells; VEGF signalling is normalized when wild‐type ANTXR1 is overexpressed in hemangioma cells. These findings suggest that ANTXR1 functions as a negative regulator of VEGF‐A signalling. Studies of a mouse model of the Growth Retardation, Alopecia, Pseudo‐anodontia and Optic Atrophy (GAPO) syndrome, caused by the loss‐of‐function mutations in ANTXR1, as well as knock‐in mice carrying the Ala‐to‐Thr ANTXR1 mutation, confirm that ANTXR1 functions as a suppressor of VEGF‐A signalling. Cutaneous endothelial cells isolated from ANTXR1‐deficient mice exhibit low levels of VEGFR1, elevated levels of VEGF‐A, HIF‐1α and CxCl12 and activated VEGFR2 signalling as in hemangioma. Increased numbers of myeloid cells in the skin of ANTXR1‐deficient mice are associated with reduced vascularity and increased skin fibrosis, suggesting a mechanism for hemangioma involution and replacement by fibrotic scars. Through controlling VEGF‐A signalling and extracellular matrix synthesis, ANTXR1 is emerging as a key regulator of skeletal and connective tissue development and homeostasis.