bluuebunny/crossref_metadata_2025 huggingface dataset:
Buprenorphine for the treatment of posttraumatic stress disorder
Authors: Lake Elizabeth P. , Mitchell Brian G. , Shorter Darryl I. , Kosten Thomas , Domingo Coreen B. , Walder Annette M.
Published: January 2019

Background and Objectives

The core pharmacological treatment of Post‐Traumatic Stress Disorder (PTSD) is selective serotonin reuptake inhibitors (SSRIs), although remission is only around 30% with them. Many patients will self‐treat with opioids and due to the opiate system involvement in dysphoric mood and anxiety/stress responses, it is likely that antagonism of the kappa opioid receptor (KOR) system represents a potential target for treatment of PTSD. The aim of this study is to compare response of PTSD symptoms when antagonizing KOR via buprenorphine/naloxone compared to SSRIs or opioid therapy.

Methods

A retrospective chart review of patients in the MEDVAMC between June 1, 2010 and June 30, 2016 was conducted. Inclusion criteria included patients with a documented diagnosis of PTSD with at least two documented PTSD scores (either PCLC or PC‐PTSD). Exclusion criteria included patients not prescribed one of the study medications (ie, buprenorphine, SSRI, or opiate for chronic pain), and patients not on the study medication for at least 30 days.

Results

Buprenorphine patients exhibited the lowest final average PTSD score (2.47) and the largest change from baseline (−24.0%) compared to opioids (−16.1%) or SSRIs (1.16%). The average buprenorphine dose was 23.3 mg/day, and the average length of therapy was 860 days.

Conclusions

Buprenorphine may help decrease PTSD symptoms more than SSRIs or opioids alone. Prospective studies are needed to determine whether these effects are reproducible.

Scientific Significance

Pharmacotherapy advancements in PTSD treatment have been limited and the kappa opioid receptor system presents a new target that warrants further research. (Am J Addict 2019;XX:1–6)
Comparison of opioid use disorder among male veterans and non‐veterans: Disorder rates, socio‐demographics, co‐morbidities, and quality of life
Authors: Rhee Taeho Greg , Rosenheck Robert A.
Published: January 2019

Background and Objectives

Amidst a surging national crisis of opioid use, concern has been expressed about its impact on veterans, but no study has presented a population‐based comparison of opioid use disorder (OUD) among veterans and non‐veterans. We analyzed national epidemiologic data to compare rates, correlates and impacts of the opioid crisis on male veterans and non‐veterans.

Methods

Restricted data from 2012 to 2013 National Epidemiologic Survey on Alcohol and Related Conditions‐III (NESARC‐III) were used to compare veteran and non‐veteran men on rates of OUD, as well as correlates of OUD including socio‐demographic characteristics, psychiatric and substance use co‐morbidities, and reductions in health‐related quality of life (HRQOL).

Results

About 2.0% of veterans and 2.7% of non‐veterans, estimated at 418,000 and 2.5 million men, respectively, met criteria for life‐time OUD. In both groups, OUD was associated with younger age, lower income levels, and fewer years of education. OUD was associated minority race among veterans, but with non‐Hispanic white race among non‐veterans. Both veteran and non‐veteran adults with OUD were at least five times more likely than their peers to have both psychiatric and substance use co‐morbidities (p < .001) and they experienced strongly reduced HRQOL scores (Cohen's d = −.50 to −.93).

Discussion and Conclusion

Veterans and non‐veterans experience similar risk of OUD, similar correlates and adverse HRQOL impacts suggesting that similar treatment approaches may be effective for both groups.

Scientific Significance

Our findings highlight comparable vulnerability of veterans to non‐veterans in both the risk of OUD and adverse effects on HRQOL. (Am J Addict 2018;XX:1–9)
Needs of people with dementia and their spousal carers: A study of those living in the community
Authors: Morrisby Claire , Joosten Annette , Ciccarelli Marina
Published: January 2019

Objective

To identify care and support needs, as reported by people with dementia and their spousal carers living in the community in metropolitan Western Australia.

Methods

An interpretive description approach was utilised. Semi‐structured interviews were conducted with 10 dyads of spousal carers and people with dementia. Comparative analysis was used to develop themes regarding need, which were reviewed using two focus groups of spousal carers.

Results

Three major themes were developed through analysis of data from the interviews and were refined by the focus groups: (a) environmental enablers to support care; (b) strong caring relationships; and (c) adaptation of daily life roles.

Conclusions

As dementia progresses, continued support to maintain participation in meaningful activity is needed. Strong caring relationships, knowledge and an understanding of dementia among health professionals, service providers and family members were key to maintaining support for the needs of people with dementia and their spousal carers.
Incidence of adverse events, preventability and mortality in gynaecological hospital admissions: A systematic review and meta‐analysis
Authors: Tanaka Keisuke , Eriksson Lars , Asher Rebecca , Obermair Andreas
Published: January 2019

Background

Adverse events (AEs) are unintended consequences of healthcare management that result in temporary or permanent disability, death or prolonged hospital stay. The incidence of AEs has been reported to be higher in surgical specialties compared to medical specialties but information on the incidence of AEs in gynaecology is sparse.

Aims

To collect evidence on the incidence, preventability and mortality of AEs in gynaecological hospital admissions by conducting a systematic review and meta‐analysis.

Materials and methods

A systematic search of the PubMed, EMBASE, and CINAHL electronic medical databases was performed. Identified articles were screened and a full‐text review was conducted by two independent reviewers.

Results

Of the 49 studies assessed for eligibility, three studies were included in this systematic review. Meta‐analysis showed that the incidence of AEs in gynaecological hospital admissions was 10.8% (95% CI 9.4–12.1%), preventability was 52.5% (95% CI 47.3–57.7%) and mortality was 1.2% (95% CI 0–2.5%).

Conclusions

Evidence on AEs in gynaecological hospital admissions is limited. Available evidence suggests that approximately one in ten gynaecological inpatients suffer at least one AE and half of AEs are considered preventable. Further research is needed to determine strategies regarding how the incidence of preventable AEs can be reduced.
The puzzling incidence of testicular cancer in New Zealand: what can we learn?
Authors: Gurney J. K.
Published: January 2019

Background

Testicular germ cell tumour is the most common cancer to be diagnosed among young men. In New Zealand, we have observed some puzzling trends in the epidemiology of this disease.

Methods

We have conducted a narrative review of available evidence regarding the puzzling epidemiology of testicular germ cell tumour in New Zealand and discussed the possible drivers of these trends.

Results and discussion

Whereas testicular cancer is most commonly a disease of White men, in New Zealand it is the indigenous Māori population that suffer by far the greatest rate of disease (age‐adjusted relative risk: 1.80, 95% CI 1.58–2.05). Even more curiously, the rate of testicular germ cell tumour among Māori men aged 15–44 (28/100,000) is substantially greater than for Pacific Island men (9/100,000), a rare example of divergence between these two populations in terms of the incidence of any disease (cancer or otherwise).

Our observations beg the following questions: first, why are rates of testicular germ cell tumour so much higher among Māori New Zealanders compared to the already high rates observed among European/Other New Zealanders? Second, why are rates of testicular germ cell tumour so completely divergent between Māori and Pacific New Zealanders, when these two groups typically move in parallel with respect to the incidence of given diseases? Finally, what might we learn about the factors that cause testicular germ cell tumour in general by answering these questions?

Conclusion

This review examines the possible drivers of our observed disparity, discusses their feasibility, and highlights new work that is underway to further understand these drivers.
The epididymal amyloid matrix: structure and putative functions
Authors: Cornwall G. A. , Do H. Q. , Hewetson A. , Muthusubramanian A. , Myers C.
Published: January 2019

Background

We previously demonstrated the normal mouse epididymal lumen contains a non‐pathological amyloid matrix that surrounds spermatozoa and plays important roles in sperm maturation and protection.

Objective

The objective herein was to present a review of this work, including studies showing the amyloid structures of four members of the CRES (cystatin‐related epididymal spermatogenic) subgroup are integral and essential components of the amyloid matrix.

Methods

We used conformation‐dependent reagents that recognize the cross‐β‐sheet structure characteristic of amyloid, including thioflavin S (ThS), thioflavin T (ThT), anti‐amyloid antibodies, and X‐ray diffraction, as well as negative‐stain transmission electron microscopy (TEM) to visualize amyloid structures in the epididymal lumen. Antibodies that specifically detect each CRES subgroup family member were also used in indirect immunofluorescence analysis.

Results and Discussion

The epididymal lumen contains an amyloid matrix that surrounds maturing spermatozoa and represents a functional amyloid. Alterations in the structure of the amyloid matrix by the loss of the CRES subgroup members or the overexpression of cystatin C result in epididymal pathologies, including infertility. Preliminary data suggest the epididymal amyloid matrix is structurally and functionally similar to bacterial biofilms.

Conclusion

Together, these results suggest the amyloid matrix serves important roles in epididymal function including sperm maturation and protection.
Regulating for telecommunications competition in developing countries: Papua New Guinea
Authors: Howell Bronwyn E. , Potgieter Petrus H. , Sofe Ronald
Published: January 2019

Papua New Guinea is a low‐middle income, developing, Pacific country whose telecommunications market has developed under regulatory arrangements strongly influenced by Australian policymaking. Nevertheless, it demonstrates very weak performance compared to similar low‐middle income countries. Why does a country whose regulatory regime draws on current international recommended ‘best practice’ perform so poorly? We develop an inquiry framework based on World Bank and the International Telecommunications Union guidelines for assessing the effectiveness of regulatory arrangements in a developing country. The framework takes account of developing country challenges: limited capacity, limited commitment, limited accountability, limited fiscal efficiency, and trade‐offs between factors that take account of these limits. The analysis indicates the most likely explanation for poor performance derives from lack of investment and an unstable set of ownership arrangements constraining government‐owned Telikom from being an effective competitor. Weaknesses in regulator accountability provisions may have contributed to obscuring poor performance. Introducing at least one more foreign operator will improve outcomes only with clear separation of government ownership and regulatory activities and credible commitment from political agents to refrain from interfering in operations of both the incumbent firm and regulatory agencies.
From financial repression to financial crisis? The case of China
Authors: Xu Guangdong , Gui Binwei
Published: January 2019

This study explores the connections between financial repression policies and the possibility of financial crisis, a relationship that has been overlooked in previous literature. We focus on China, a country with one of the highest levels of financial repression in the world. China's case shows that when financial repression is maintained at a modest level, as the government did before 2008, the possibility of a financial crisis is low; however, when financial repression policies are pushed to an excessive level, as the government did after 2008, the national asset‐liability structure may be damaged to such an extent that a financial crisis becomes likely. The key to understanding the changing role of China's financial repression policies lies in the survival strategy of the Chinese party‐state, which regards finance as a powerful weapon and is eager to use it to address certain economic, political, or social problems that may endanger its rule.
Letter: different risks of venous thromboembolism in subsets of patients with inflammatory bowel diseases
Authors: Ding Ru , Xu Jianjiang , He Zhiqing , Chen Yihong , Hultgårdh‐Nilsson Anna , Liang Chun
Published: January 2019

Linked Content

This article is linked to Chu et al papers. To view these articles, visit https://doi.org/10.1111/apt.15010 and https://doi.org/10.1111/apt.15103.
Comprehensive evaluation of growth performance and meat characteristics of a fattening system combining grazing with feeding rice whole‐crop silage in Japanese Black steers
Authors: Shibata Masahiro , Hikino Yasuko , Imanari Mai , Matsumoto Kazunori
Published: January 2019

We investigated the effect of a system for fattening steers combining grazing with feeding rice whole‐crop silage (rWCS) on growth performance, meat characteristics, and the expression of genes involved in skeletal muscle growth. Steers were randomly assigned to grazing or concentrate‐fed groups (CT). The grazing group (GZ) was fed rWCS after grazing until 16 months of age. The final body weight was the same in the two groups, but the dressed weight was lower in the GZ than in the CT. The beef color standard was higher in the GZ than in the CT. Although beef marbling did not differ between the two groups, there was less intramuscular fat and subcutaneous fat in the GZ than in the CT. The α‐tocopherol and β‐carotene contents in the muscle were higher in the GZ than in the CT. The GZ showed a lower daily gain (DG) during the grazing period, which may have resulted from decelerating skeletal muscle growth caused by the increased expression of genes encoding myostatin and atrogin‐1. However, the DG and feed efficiency of the GZ increased after grazing. The two groups exhibited a similar level of beef productivity.
Clinical and translational pharmacology of the cathepsin K inhibitor odanacatib studied for osteoporosis
Authors: Stone Julie A. , McCrea Jacqueline B. , Witter Rose , Zajic Stefan , Stoch S. Aubrey
Published: January 2019

Cathepsin K (CatK) is a cysteine protease abundantly expressed by osteoclasts and localized in the lysosomes and resorption lacunae of these cells. CatK is the principal enzyme responsible for the degradation of bone collagen. Odanacatib is a selective, reversible inhibitor of CatK at subnanomolar potency. The pharmacokinetics of odanacatib have been extensively studied and are similar in young healthy men, postmenopausal women and elderly men, and were qualitatively similar throughout Phase 1 development and in‐patient studies. Following 3 weeks of 50 mg once weekly dosing the geometric mean area under the curve from 0 to 168 hours was 41.1 μM h, the concentration at 168 hours was 126 nM and the harmonic mean apparent terminal half‐life was 84.8 hr. Odanacatib exposure increased in a less than dose proportional manner due to solubility limited absorption. It is estimated that approximately 70% of the absorbed dose of odanacatib is eliminated via metabolism, 20% is excreted as unchanged drug in the bile or faeces, and 10% is excreted as unchanged drug in the urine. The systemic clearance was low (approximately 13 mL/min). Odanacatib decreases the degradation of bone matrix proteins and reduces the efficiency of bone resorption with target engagement confirmed by a robust decrease in serum C‐telopeptides of type 1 collagen (approximately 60%), urinary aminoterminal crosslinked telopeptides of type 1 collagen to creatinine ratio (approximately 50%) and total urine deoxypyridinoline/Cr (approximately 30%), with an increase in serum cross‐linked carboxy‐terminal telopeptide of type 1 collagen (approximately 55%). The 50‐mg weekly dosing regimen evaluated in Phase 3 achieved near maximal reduction in bone resorption throughout the treatment period. The extensive clinical programme for odanacatib, together with more limited clinical experience with other CatK inhibitors (balicatib and ONO‐5334), provides important insights into the clinical pharmacology of CatK inhibition and the potential role of CatK in bone turnover and mineral homeostasis. Key findings include the ability of this mechanism to: (i) provide sustained reductions in resorption markers, increases in bone mineral density, and demonstrated fracture risk reduction; (ii) be associated with relative formation‐sparing effects such that sustained resorption reduction is achieved without accompanying meaningful reductions in bone formation; and (iii) lead to increases in osteoclast number as well as other osteoclast activity (including build‐up of CatK enzyme), which may yield transient increases in resorption following treatment discontinuation and the potential for nonmonotonic responses at subtherapeutic doses.
Long‐term survival rates of patients undergoing vitrectomy for diabetic retinopathy in an Australian population: a population‐based audit
Authors: Liu Ebony , Estevez Jose , Kaidonis Georgia , Hassall Mark , Phillips Russell , Raymond Grant , Saha Niladri , Wong George H.C. , Gilhotra Jagjit , Burdon Kathryn , Landers John , Henderson Tim , Newland Henry , Lake Stewart , Craig Jamie E.
Published: January 2019

Importance

Five‐year survival rates in patients undergoing vitrectomy for diabetic retinopathy (DR) vary from 68% to 95%. No study has been conducted in an Australian population.

Background

We aimed to determine the survival rates of patients undergoing diabetic vitrectomy in an Australian population.

Design

Retrospective audit, tertiary centre hospitals and private practices.

Participants

All individuals in South Australia and the Northern Territory who underwent their first vitrectomy for diabetic complications between January 1, 2007 and December 31, 2011.

Methods

An audit of all eligible participants has been completed previously. Survival status as of July 6, 2018 and cause of death were obtained using SA/NT DataLink. Kaplan‐Meier survival curves and multivariate cox‐regressions were used to analyse survival rates and identify risk factors for mortality.

Main outcome measures

Five‐, seven‐ and nine‐year survival rates.

Results

The 5‐, 7‐ and 9‐year survival rates were 84.4%, 77.9% and 74.7%, respectively. The most common cause of death was cardiovascular disease. Associated with increased mortality independent of age were Indigenous ethnicity (HR = 2.04, 95% confidence interval [CI]: 1.17‐3.57, P = 0.012), chronic renal failure (HR = 1.76, 95% CI: 1.07‐2.89, P = 0.026) and renal failure requiring dialysis (HR = 2.32, 95% CI: 1.25‐4.32, P = 0.008).

Conclusions and relevance

Long‐term survival rates after diabetic vitrectomy in Australia are similar to rates reported in other populations. Indigenous ethnicity and chronic renal failure were the most significant factors associated with long‐term mortality. This information can guide allocation of future resources to improve the prognosis of these high risk groups.
Choroidal structure in subtypes of polypoidal choroidal vasculopathy determined by binarization of optical coherence tomographic images
Authors: Liu Bing , Zhang Xiongze , Mi Lan , Peng Yuting , Wen Feng
Published: January 2019

Importance

Chorodial structure in subtypes of polypoidal choroidal vasculopathy (PCV).

Background

To evaluate choroidal vascularity in the eyes of patients with PCV with and without choroidal vascular hyperpermeability (CVH).

Design

A hospital‐based retrospective study.

Participants

Fifty‐eight PCV patients (28 with CVH; 30 without CVH) and 30 normal controls were included in this study.

Methods

All study subjects underwent spectral‐domain optical coherence tomography with enhanced depth imaging, and the choroidal images were binarized into the luminal area and stromal area.

Main Outcome Measures

Choroidal vascularity index (CVI) and subfoveal choroidal thickness (SFCT).

Results

Compared to normal controls, patients with PCV showed no obvious difference in SFCT (P = 0.510), but significantly lower CVI (P = 0.003). Among PCV patients, the CVI in eyes with CVH was significantly greater than that in those without CVH (65.78 ± 4.70 vs 62.28 ± 3.90; P = 0.002), and a significant difference in SFCT was also found between the two subtypes of PCV (340.8 ± 89.2 vs 250.4 ± 67.7; P < 0.001).

Conclusions and Relevance

PCV eyes with CVH have a greater CVI and a thicker SFCT than those without CVH. The significant differences in choroidal vascularity between the two subtypes of PCV may broaden our understanding of the pathogenesis of this disease and contribute to significant improvements in treatment.
The Liverpool Peritonsillar abscess Score: Development of a predictive score through a prospective multicentre observational study
Authors: Lau Andrew S. , Selwyn David M. , Yang Ding , Swainbank Liam , Ridley Paul , Carmichael Nicola , Metcalfe Christopher , Watson George , Emerson Hannah
Published: January 2019

Objectives

While uncommon in the population at large, peritonsillar abscess (PTA) is a common subject of ENT referrals. Missed or uncertain diagnosis is a source of concern for non‐specialist referrers. In line with the NHS England Second Sepsis Action Plan, we aimed to develop a predictive score for the presence of PTA. This would help to improve non‐specialist colleagues’ diagnostic certainty as well as to support ENT surgeons’ triage of these referrals.

Design

Prospective, multicentre observational study.

Setting

Primary and secondary care.

Participants

Patients >16 years with symptoms of sore throat.

Data

We prospectively collected comprehensive data on patient demographics, symptoms and clinical status. We documented whether the patient had aspiration‐proven PTA or not. We performed binary logistic regression analysis, iterative development of a predictive score which we validated internally.

Results

100 patients were included (46 PTA and 54 tonsillitis). Five variables added significantly to the logistic regression model: unilateral sore throat; trismus; male gender; pharyngeal voice change; and uvular deviation. Using the odds ratio outputs, we developed the Liverpool Peritonsillar abscess Score (LPS) iteratively. We validated the latest (third) iteration of the LPS internally (ie, on the same sample), yielding sensitivity 96%; specificity 85%; positive predictive value 85%; and negative predictive value 96%. The area under the receiver operating characteristics (AUROC) curve was 0.970.

Conclusions

We have developed the first predictive score for PTA based on symptoms and signs that do not require the user to have specialist experience. Its high negative predictive value may be particularly helpful to non‐specialist colleagues.
Concomitant contact‐allergic reactions to iodopropynyl butylcarbamate and iodine
Authors: Vanhoutte Charlotte , Goossens An , Gilissen Liesbeth , Huygens Sarah , Vital‐Durand Dominique , Dendooven Ella , Aerts Olivier
Published: January 2019

Background

Iodopropynyl butylcarbamate (IPBC) is a broad‐spectrum preservative for use in several product types, including cosmetics, in which its concentrations have been limited by EU legislation because of concerns related to its iodine content and release, and the risk of subsequent iodine overdose.

Objectives

To report on concomitant patch test reactions observed with iodine and IPBC in patients sensitized to iodine‐containing antiseptics.

Patients

Between 2012 and 2018, seven patients, six from Belgium and one from France, two suffering from acute dermatitis during surgical interventions, four from dermatitis caused by wound treatment, and one from occupational dermatitis, were shown to be sensitized to iodine and/or povidone‐iodine (PVP‐I), which was considered to be relevant for their dermatitis. All patients were coincidentally also patch tested with IPBC.

Results

All patients showed positive patch test reactions to several other allergens, including IPBC. No relevance could be detected for IPBC.

Conclusions

We suspect that, notwithstanding the absence of firm evidence for IPBC being dehalogenated to produce free iodine in animals or in humans, the patch test reactions to IPBC in iodine‐allergic subjects were possibly caused by free iodine released from this preservative agent, thus underlining the EU restrictions regarding the use of this preservative in cosmetics.
PENSION CONTRIBUTIONS, PENSION AWARENESS, AND CHANGING PERSONAL FINANCES
Authors: Lay Margaret J.
Published: January 2019

Workers with 401(k)s and similar defined contribution pensions adjust contributions facing large fluctuations in personal finances. Using administrative tax records linked to the Health and Retirement Study, this paper shows that adjustments differ for contributors who are aware and unaware of their pension coverage. Unaware contributors are more likely to stop contributing facing deteriorating finances, but adjust contributions similarly along the intensive margin. For example, 25% of unaware contributors stop contributing facing earnings declines, but only 15% of aware contributors do so. These findings have implications for policies like automatic enrollment and information campaigns that encourage retirement savings. (JEL D14, J14, J32, D83)
Nipple leiomyoma: A rare neoplasm with a broad spectrum of histologic appearances
Authors: Hammer Phoebe , White Kevin , Mengden Stephanie , Korcheva Vessy , Raess Philipp W.
Published: January 2019

Cutaneous leiomyomas are rare benign smooth‐muscle tumors. These lesions are distinguished based on their cell of origin and are subclassified as pilar leiomyoma, angioleiomyoma, and genital‐type leiomyoma. Nipple leiomyoma is the least common genital‐type leiomyoma, arising from the dartoic muscle cell of the nipple. Histologic examination of the lesion is necessary for definitive diagnosis, and these uncommon tumors can pose a diagnostic challenge. We describe herein a series of six nipple leiomyomas with a spectrum of histologic appearances.
Does Information Technology Substitute for or Complement Human Labor? A Dynamic Stratified Analysis on European Countries
Authors: Peng Gang , Zhang Dawei (David)
Published: January 2019

The interaction between information technology (IT) and human labor in manufacturing and service provision has always been a topic of much debate. Anchored from the skill‐biased technological change theory and the organizational complementarity theory, this study proposes a dynamic stratified analysis and argues that the relationship between IT and labor is more nuanced than what has been conceptualized in prior literature. We find that IT can not only substitute for human labor but also can complement it—the exact nature depends on the skill levels of the labor. In addition, as the capability of IT continues to grow, the substitution/complementarity relationship between IT and labor evolves over time. We test our hypotheses using the EU KLEMS dataset covering 31 industries from 13 EU countries from year 1970 to 2005. The findings shed light on the nature of interaction between IT and human labor and contribute to both the information systems literature and the operations management literature by providing a deeper understanding on how IT can influence labor input, tasks, jobs, and productivity.
Submucosal painting for gastroduodenal stent placement
Authors: Morita Shinichi , Suda Takeshi , Terai Shuji
Published: January 2019

Watch a video of this article
Time in a bottle: challenges to disaster studies in Latin America and the Caribbean
Authors: Alcántara‐Ayala Irasema
Published: January 2019

LA RED (Network of Social Studies on the Prevention of Disasters in Latin America) has become the most influential group analysing disasters in Latin America and the Caribbean. Its contributions have paved the way for a new way of understanding disasters, disaster risk, and their management, concerning: (i) that disasters are not natural, but socially constructed; (ii) the inherent nexus between disaster risk, development, and the environment; (iii) the significance of small‐ and medium‐sized disasters and extensive and intensive risks; (iv) disaster risk management at the local level; and (v) integrated disaster risk research and the need for forensic investigations of disasters. As a result of this unification of challenges, intellectual communities of connected individuals were formed. Nonetheless, a focus on territorial management, exposure, and vulnerability remains a challenge for academia. In addition, the labyrinths of disaster risk governance must be disentangled by other stakeholders, such as national authorities, policymakers, and practitioners.
Clinical features of facioscapulohumeral muscular dystrophy 1 in childhood
Authors: Steel Dora , Main Marion , Manzur Adnan , Muntoni Francesco , Munot Pinki
Published: January 2019

Aim

To explore the clinical course of patients presenting with facioscapulohumeral dystrophy type 1 (FSHD1) in childhood, with a view to identifying areas where they differed from older patients and where extra support or monitoring might be required.

Method

A retrospective case‐notes review of children with FSHD1 seen at a tertiary paediatric neuromuscular centre between 2002 and 2016 was performed. Data collected included age at and nature of presentation, path to diagnosis, genetic testing results, motor function, and occurrence of extramuscular features and complications.

Results

Eighteen children (11 females, seven males; mean [SD] age at latest review 13y 10mo [3y 9mo], range 8–19y) from 16 families were identified. Age at onset of FSHD1 correlated with the size of deletion (r=0.81) and most presentations were in children either younger than 5 years or older than 10 years. Children with onset before 5 years were more likely to present with non‐muscular symptoms and to develop extramuscular pathology, including developmental and psychiatric issues, hearing or visual impairments, and problems involving respiratory function and nutrition. No cases of epilepsy or cardiac arrhythmia were identified but two children died.

Interpretation

The complexity and severity of FSHD1 presenting in early childhood underlines the importance of a multidisciplinary approach to the disorder.

What this paper adds

Young children often present with non‐muscular pathology in facioscapulohumeral dystrophy type 1 (FSHD1), especially hearing loss.

Age at onset in paediatric FSHD1 appears bimodal: under 5 years or in adolescence.

Prolonged delays to diagnosis are common.

Children with very early‐onset FSHD1 may require nutritional and/or respiratory support.

Developmental and psychiatric comorbidities are common.
Prevalence of metabolic syndrome and cardiovascular disease risk factors in adults with cerebral palsy
Authors: Heyn Patricia C , Tagawa Alex , Pan Zhaoxing , Thomas Sruthi , Carollo James J
Published: January 2019

Aim

To investigate the prevalence of metabolic syndrome and cardiovascular disease (CVD) risk factors and the association between common metabolic markers and Gross Motor Function Classification System (GMFCS) levels in ambulatory adults with cerebral palsy (CP).

Method

Metabolic markers and GMFCS levels were evaluated in a cross‐sectional study of 70 ambulatory adults with CP (34 males, 36 females; mean age 24y 5mo [SD 5y 4mo], range 18y 6mo–48y 8mo) to determine the prevalence of metabolic syndrome and CVD risk factors, and were compared to age‐matched, population norms from the National Health and Nutrition Examination Survey (NHANES) registry. The Framingham Heart Study (FHS) CVD risk estimation was also used to evaluate an individual's risk for CVD.

Results

Metabolic syndrome was identified in 17.1% of the cohort, higher than the 10% in the NHANES registry. The FHS CVD 30‐year lipid and body mass index (BMI)‐based risk factor results showed that 20% to 40% of the cohort was at greater risk of developing CVD (BMI‐based: 39.7% ‘full’ CVD risk factor; lipid‐based: 26.5% ‘full’ CVD risk factor) as compared to the FHS normative population data. There was a positive correlation between GMFCS level, waist circumference (r=0.28, p=0.02), and waist‐to‐hip ratio (r=0.28, p=0.02).

Interpretation

Adults with CP are at higher risk of CVD and metabolic syndrome compared to the general population, which is probably because of impaired mobility.

What this paper adds

Gross Motor Function Classification System levels can predict cardiovascular disease (CVD) risk factors in adults with cerebral palsy (CP).

Anthropometric measures are significant in predicting CVD risk factors in adults with CP.

Early CVD screening and ongoing risk factor monitoring are important in adults with CP.
Pleiotropic effects of liraglutide in patients with type 2 diabetes and moderate renal impairment: Individual effects of treatment
Authors: Zobel Emilie H. , von Scholten Bernt J. , Goldman Bryan , Persson Frederik , Hansen Tine W. , Rossing Peter
Published: January 2019

Liraglutide has pleiotropic effects favouring cardiovascular and renal risks. We investigated individual responses to liraglutide in six cardio‐renal risk factors to examine whether responses in one risk factor are associated with changes in other risk factors (cross‐dependency). We performed secondary analysis of the LIRA‐RENAL trial (n = 279) in type 2 diabetes. HbA1c, body weight, systolic blood pressure (SBP), low density lipoprotein (LDL)‐cholesterol, urine albumin‐to‐creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were measured at baseline and after 26 weeks of liraglutide/placebo treatment: “Good responders” had a change within the best quartile. In the liraglutide‐treated group, good HbA1c responders showed similar changes in other risk factors analysed to low responders (P ≥ 0.17). Good body weight responders had a larger reduction in HbA1c than low body weight responders (−1.6 ± 0.94 vs. –1.0 ± 0.82%; P = 0.003), but similar changes in the other risk factors (P ≥ 0.11). Good and low responders in SBP, UACR, LDL‐cholesterol or eGFR showed similar changes in other risk factors (P ≥ 0.07). Treatment response to liraglutide is largely individual; aside from an association between body weight and HbA1c reduction, there are no obvious cross‐dependencies in risk factor response.
One‐hour post‐load plasma glucose predicts progression to prediabetes in a multi‐ethnic cohort of obese youths
Authors: Tricò Domenico , Galderisi Alfonso , Mari Andrea , Santoro Nicola , Caprio Sonia
Published: January 2019

AIMS

One‐hour post‐load hyperglycaemia has been proposed as an independent predictor of type 2 diabetes in adults. We examined whether 1‐hour plasma glucose (1hPG) during an oral glucose tolerance test (OGTT) can predict changes in the glucose tolerance status of a multi‐ethnic cohort of youths with normal glucose tolerance (NGT).

Materials and methods

A total of 202 obese youths with NGT (33.7% Caucasian, 31.1% Hispanic, 32.2% African American) underwent a 3‐hour OGTT at baseline and after a 2‐year follow‐up period. Whole‐body insulin sensitivity, insulin secretion, β‐cell function and insulin clearance were estimated by modeling plasma glucose, insulin and C‐peptide levels.

Results

Obese youths with 1hPG ≥7.4 mmol/L (or 133 mg/dL; n = 83) exhibited higher body mass index (BMI), plasma triglycerides and fasting and post‐load glucose concentrations than individuals with 1hPG <7.4 mmol/L. Also, 1hPG ≥7.4 mmol/L was associated with a lower disposition index (DI) (P < 0.0001) and with alterations in whole‐body insulin sensitivity, β‐cell function and insulin clearance. Adolescents with 1hPG ≥7.4 mmol/L were approximately three times more likely to develop prediabetes (ie, impaired glucose tolerance and/or impaired fasting glucose) over time (OR, 2.92 [1.22‐6.98]; P = 0.02), independent of age, sex, race/ethnicity, BMI, insulin sensitivity, DI and plasma glucose concentrations. No differences emerged in the risk of prediabetes related to 1‐hour hyperglycaemia among different ethnic groups.

Conclusions

A plasma glucose concentration ≥ 7.4 mmol/L at 1 hour during an OGTT is associated with a worse clinical and metabolic phenotype and may be an independent predictor of progression to prediabetes in obese youths with NGT.
Two conifer species native to Patagonia threatened by Phytophthora austrocedri
Authors: Taccari Leonardo E. , Greslebin Alina G. , Salgado Salomón María E. , Vélez María L.
Published: January 2019

Phytophthora austrocedri is a pathogen of Austrocedrus chilensis causing “Mal del Ciprés” (cypress sickness) in Patagonia and killing Juniperus communis in Britain, along with other species in the Cupressaceae. The evident association of the pathogen with members of the Cupressaceae makes it necessary to study the susceptibility of other species related to A. chilensis to prevent the emergence of new diseases. The present study tested the pathogenicity of P. austrocedri to three native and endemic conifers in South America: Fitzroya cupressoides, Pilgerodendron uviferum and Araucaria araucana. The results showed that F. cupressoides and P. uviferum were highly susceptible to P. austrocedri. Since these are endangered tree species, the outcome of this study is crucial for governmental agencies, policymakers and stakeholders.
Single versus double‐unit transfusion: Safety and efficacy for patients with hematologic malignancies
Authors: Bowman Zelia , Fei Naomi , Ahn Janice , Wen Sijin , Cumpston Aaron , Shah Nilay , Craig Michael , Perrotta Peter L. , Kanate Abraham S.
Published: January 2019

Objectives

Although hemoglobin thresholds for red blood cell (RBC) transfusion have decreased, double‐unit RBC transfusion practices persist. We studied the effects switching from predominantly double‐unit to single‐unit RBC transfusions had on utilization and clinical outcomes for malignant hematology patients.

Methods

Retrospective chart review compared malignant hematology patients before and after implementing single‐unit RBC transfusion policy. Hemoglobin threshold was 8.0 g/dL for both groups. RBC utilization metrics included number of RBC units transfused, RBC units transfused per admission, and number of transfusion episodes. Clinical outcomes included length of stay, 30‐day mortality, and outpatient RBC transfusion 30‐days post‐discharge.

Results

Baseline hemoglobin was similar in both groups. The single‐unit group was transfused with fewer RBC units per admission (5.1 vs 4.5, P = 0.01) than the double‐unit group, but had more transfusion episodes per admission (4.1 vs 2.7, P < 0.001). After implementing single‐unit policy, a 29% reduction in RBC utilization was observed. Mean hemoglobin at discharge was lower in the single‐unit group (8.9 vs 9.5 g/dL, P = 0.005). No significant differences in length of stay or 30‐day mortality were observed.

Conclusion

Transfusing malignant hematology patients with single RBC units is safe and efficacious. Electronic provider order systems facilitating RBC transfusion requests provide excellent adherence to transfusion policy.
Insight into the complex pathophysiology of sickle cell anaemia and possible treatment
Authors: Piccin Andrea , Murphy Ciaran , Eakins Elva , Rondinelli Maria Beatrice , Daves Massimo , Vecchiato Cinzia , Wolf Dominik , Mc Mahon Corrina , Smith Owen P.
Published: January 2019

Sickle cell anaemia (SCA) is the consequence of abnormal haemoglobin production due to an inherited point mutation in the β‐globin gene. The resulting haemoglobin tetramer is poorly soluble when deoxygenated, and when this is prolonged, intracellular gelation of sickle haemoglobin occurs, followed by haemoglobin polymerisation. If many cycles of sickling and unsickling occur, the red cell membrane will be disrupted leading to haemolysis and vaso‐occlusive events. Recent studies have also shown that leucocyte adhesion molecules and nitric oxide (NO) depletion are involved in endothelial damage. New insights in SCA pathophysiology and vascular biology have shown that cell‐derived microparticle (MP) generation is also involved in the vaso‐occlusion. Endothelial damage is perpetuated by impaired production or increased consumption of protective modulators such as protein C, protein S and NO. New therapeutic interventions should address these aspects of SCA pathogenesis. To date, the only US‐FDA‐approved therapy to prevent painful vaso‐occulsive episodes is hydroxyurea that reduces haemoglobin polymerisation in sickle cells by increasing the production of foetal haemoglobin and L‐glutamine. However, several new drugs have been tested in the last years in randomised clinical trials. We here report an update on the current status of knowledge on SCA.
Improving the SVM gender classification accuracy using clustering and incremental learning
Authors: Dagher Issam , Azar Fady
Published: January 2019

Gender recognition has been playing a very important role in various applications such as human–computer interaction, surveillance, and security. Nonlinear support vector machines (SVMs) were investigated for the identification of gender using the Face Recognition Technology (FERET) image face database. It was shown that SVM classifiers outperform the traditional pattern classifiers (linear, quadratic, Fisher linear discriminant, and nearest neighbour). In this context, this paper aims to improve the SVM classification accuracy in the gender classification system and propose new models for a better performance. We have evaluated different SVM learning algorithms; the SVM‐radial basis function with a 5% outlier fraction outperformed other SVM classifiers. We have examined the effectiveness of different feature selection methods. AdaBoost performs better than the other feature selection methods in selecting the most discriminating features. We have proposed two classification methods that focus on training subsets of images among the training images. Method 1 combines the outcome of different classifiers based on different image subsets, whereas method 2 is based on clustering the training data and building a classifier for each cluster. Experimental results showed that both methods have increased the classification accuracy.
Ran1 is essential for parental macronuclear import of apoptosis‐inducing factor and programmed nuclear death in Tetrahymena thermophila
Authors: Liang Haixia , Xu Jing , Wang Wei
Published: January 2019

During programmed nuclear death (PND), apoptosis‐inducing factor (AIF) translocates from mitochondria to the parental macronucleus (MAC) in Tetrahymena thermophila. In the degenerating parental MAC, AIF induces chromatin condensation and large‐scale DNA fragmentation in a caspase‐independent manner. However, the regulation of AIF nuclear translocation and molecular mechanism of PND are less clear. In this study, we demonstrated that the asymmetric distribution of nuclear GDP‐bound Ran1‐mimetic mutant Ran1T25N and cytoplasmic GTP‐bound Ran1‐mimetic mutant Ran1Q70L exists across the parental macronuclear‐cytoplasmic barrier during PND. Knockdown of RAN1 led to defects in PND progression and failure of parental macronuclear accumulation of AIF. Moreover, AIF parental macronuclear import occurred in Ran1T25N mutants, while it was inhibited in Ran1Q70L mutants. Importantly, artificial accumulation of AIF in the parental MAC rescued PND progression defects in RAN1 knockdown mutants. These data suggest that Ran1 is essential for parental macronuclear import of AIF and PND in T. thermophila.
Kinetic and mechanistic studies of p38α MAP kinase phosphorylation by MKK6
Authors: Wang Yu‐Lu , Zhang Yuan‐Yuan , Lu Chang , Zhang Wenhao , Deng Haiteng , Wu Jia‐Wei , Wang Jue , Wang Zhi‐Xin
Published: January 2019

Bistability (coexistence of two stable steady states in a dynamical system) is a key mechanism of cellular decision‐making and has been observed in many biochemical reaction networks such as mitogen‐activated protein kinase (MAPK) signaling pathways. Theoretical studies have shown that bistability can arise in a single two‐site MAPK phosphorylation and dephosphorylation cycle. However, the bistable behavior mostly relies on the kinetic mechanisms and parameters of this two‐site modification. In exploring the system‐level properties of MAPK regulation, most models to date focus on two limiting reaction regimes, distributive and processive, and are characterized by high levels of parametric uncertainty. Here, we developed a combined kinetic method which applies a continuous spectrophotometric enzyme‐coupled assay incorporated with the viscosity approach, to perform detailed kinetic analyses of p38α MAPK dual phosphorylation by MKK6. Almost all kinetic rate constants for the first and second phosphorylation steps in p38α activation have been quantitatively determined, supporting that the phosphorylation occurs randomly in the first step, albeit preferring the tyrosine residue. The release rates of monophosphorylated p38α from MKK6, either as the product in the first modification or as the substrate in the second step, were comparable to the respective adjacent phosphoryl transfer steps. These results indicated that dual phosphorylation of p38α by MKK6 involves a random, partially processive mechanism. Based on the experimentally determined models and parameters, dynamics of the p38α‐MKK6‐MKP5 system were explored, demonstrating for the first time that bistability can arise with this model at biologically feasible parameter values.

Enzymes

p38α (EC 2.7.11.24); MKK6 (EC 2.7.12.2).
Persistently rare species experience stronger negative frequency dependence than common species: A statistical attractor that is hard to avoid
Authors: Rovere Jacob , Fox Jeremy W.
Published: January 2019

Aim

Why are so many species rare, yet persistent? Possibly, rare species experience strong negative frequency dependence (NFD, i.e. strong intraspecific competition relative to interspecific competition), which both makes them rare and buffers them against extinction. A second, not mutually exclusive, possibility is that rare species that experience weak NFD go extinct quickly due to demographic and environmental stochasticity. Both possibilities predict that persistent rare species will experience stronger NFD than common ones. A previous study confirmed this prediction in a range of mostly terrestrial communities. Here, we test that prediction in lake zooplankton and explore its theoretical basis.

Location

Fifty‐three temperate lakes.

Time period

1970–2011.

Major taxa studied

Cladocerans, copepods.

Methods

We used long‐term time series data to estimate the covariance between strength of NFD and mean frequency (relative abundance) for crustacean zooplankton. We used a randomization test to ask whether the covariance between NFD and mean frequency is stronger than expected, given sampling error. We also calculated the covariance between NFD and mean frequency in simulated communities from three different ecological models.

Results

Rare species experience significantly stronger NFD than common species in over half of the communities. The distribution of associations between NFD and rarity is skewed towards weak associations, which always occur in communities with high evenness. All three theoretical models reproduce these empirical results, even though they are based on different mechanisms (demographic or environmental stochasticity, and mathematical constraints on possible NFD–frequency relationships).

Main conclusions

Rare species typically experience stronger NFD than common ones because there are many different ecological scenarios in which they will do so, and only a few scenarios in which they won’t. Like several other macroecological patterns, the tendency for rare species to experience stronger NFD than common ones is a “statistical attractor” that is hard to avoid.