bluuebunny/crossref_metadata_2025 huggingface dataset:
Variation in thermal niche of a declining river‐breeding frog: From counter‐gradient responses to population distribution patterns
Authors: Catenazzi Alessandro , Kupferberg Sarah J.
Published: May 2017

When dams or climate change alter the thermal regimes of rivers, conditions can shift outside optimal ranges for aquatic poikilothermic vertebrates. Plasticity in thermal performance and preference, however, may allow temperature‐vulnerable fauna to persist under challenging conditions.

To determine the effects of thermal regime on Rana boylii (Ranidae), a threatened frog species endemic to rivers of California and Oregon, we quantified tadpole thermal preferences and performance in relation to thermal conditions. We monitored temperature and censused populations across a coastal to inland cline in six catchments where dams have altered thermal environments in close proximity to river reaches with natural conditions.

We found geographic variation in population distribution and abundance based on river size combined with water temperature. The large inland rivers that supported breeding frogs, although cooler in spring due to snowmelt, became warmer during the summer than occupied coastal sites. Inland populations were constrained to reaches where the average temperature over the warmest 30 days ranged from 17.6 to 24.2°C, higher than coastal rainfall‐driven systems where averages ranged from 15.7 to 22.0°C. Frogs in rivers with hypolimnetic‐release dams bred in colder waters than they did in free‐flowing rivers.

Common‐garden and field translocation experiments revealed local adaptations in larval growth and phenotypically plastic thermoregulatory behaviour. Tadpoles from all rivers had a positive linear growth response to temperature, but individuals from inland rivers displayed intrinsically higher growth rates. Consistent with a counter‐gradient model of selection in which the response to temperature change is in the opposite direction of the change, individuals from cooler rivers selected warmer temperatures. When reared under common conditions, however, tadpoles showed similar temperature preferences regardless of source river.

Our results suggest a role for local growth rate adaptation in structuring the distribution of Rana boylii. Plastic thermoregulatory behaviour by tadpoles may explain how small populations are able to persist where dams release cold water. Management of edgewater habitats to increase the availability of warm micro‐sites may ameliorate this impact.
Delayed coral recovery in a warming ocean
Authors: Osborne Kate , Thompson Angus A. , Cheal Alistair J. , Emslie Michael J. , Johns Kerryn A. , Jonker Michelle J. , Logan Murray , Miller Ian R. , Sweatman Hugh P. A.
Published: May 2017

Climate change threatens coral reefs across the world. Intense bleaching has caused dramatic coral mortality in many tropical regions in recent decades, but less obvious chronic effects of temperature and other stressors can be equally threatening to the long‐term persistence of diverse coral‐dominated reef systems. Coral reefs persist if coral recovery rates equal or exceed average rates of mortality. While mortality from acute destructive events is often obvious and easy to measure, estimating recovery rates and investigating the factors that influence them requires long‐term commitment. Coastal development is increasing in many regions, and sea surface temperatures are also rising. The resulting chronic stresses have predictable, adverse effects on coral recovery, but the lack of consistent long‐term data sets has prevented measurement of how much coral recovery rates are actually changing. Using long‐term monitoring data from 47 reefs spread over 10 degrees of latitude on Australia's Great Barrier Reef (GBR), we used a modified Gompertz equation to estimate coral recovery rates following disturbance. We compared coral recovery rates in two periods: 7 years before and 7 years after an acute and widespread heat stress event on the GBR in 2002. From 2003 to 2009, there were few acute disturbances in the region, allowing us to attribute the observed shortfall in coral recovery rates to residual effects of acute heat stress plus other chronic stressors. Compared with the period before 2002, the recovery of fast‐growing Acroporidae and of “Other” slower growing hard corals slowed after 2002, doubling the time taken for modest levels of recovery. If this persists, recovery times will be increasing at a time when acute disturbances are predicted to become more frequent and intense. Our study supports the need for management actions to protect reefs from locally generated stresses, as well as urgent global action to mitigate climate change.
Association between body composition parameters and risk of mild cognitive impairment in older Japanese adults
Authors: Bae Seongryu , Shimada Hiroyuki , Park Hyuntae , Lee Sangyoon , Makizako Hyuma , Doi Takehiko , Yoshida Daisuke , Tsutsumimoto Kota , Anan Yuya , Suzuki Takao
Published: May 2017

Aim

The aim of the present study was to investigate the association between various body composition parameters and the risk of mild cognitive impairment (MCI) in older Japanese adults, as well as potential sex‐related differences in the risk of MCI.

Methods

Participants underwent cognitive tests, and were divided into 840 participants with MCI (mean age 71.9 ± 5.5 years) and 1740 without MCI (mean age 71.3 ± 5.2 years). Body composition parameters were measured using a bioelectrical impedance analyzer. Multiple logistic regression analysis was then carried out to examine the associations between body composition parameters and risk of MCI.

Results

After adjusting for confounding factors, those in the lowest quartile for fat‐free mass had a higher risk of MCI than those in the highest quartile (men: odds ratio [OR] 1.96, 95% confidence interval CI 1.24–3.10; women: OR 1.49, 95% CI 1.01–2.19). Loss of muscle mass in the upper (OR 2.17, 95% CI 1.40–3.37) and lower (OR 1.99, 95% CI 1.25–3.15) limbs was associated with a higher MCI risk in men. However, only loss of muscle mass in the lower limbs was associated with a higher MCI risk (OR 1.61, 95% CI 1.06–2.44) in women. No associations were found between obesity measures and MCI.

Conclusions

We found that loss of fat‐free mass was associated with MCI in older adults, regardless of sex. We also found that appendicular muscle mass was more closely associated with MCI in men than in women. These results suggest that the association between appendicular muscle mass and MCI might have different underlying mechanisms based on sex. Geriatr Gerontol Int 2017; 17: 2053–2059.
Case of Mycobacterium mucogenicum in a home hemodialysis patient
Authors: Dhruve Miten J. , Bunce Paul E. , D'Gama Celine , Chan Christopher T
Published: May 2017

We present a case of a patient on home hemodialysis who developed Mycobacterium mucogenicum bacteremia. While infections with this particular organism are rare, disseminated infections have been reported and have been associated with significant morbidity and mortality. Diagnosis required appropriate cultures, understanding of natural habitat of organism and complete environmental analysis including blood, dialysis sample port, reverse osmosis and incoming water supply cultures. The patient was treated successfully with systemic antibiotics, removal of central venous catheter, patient education and complete exchange of the hemodialysis circuit.
PACAP38: Emerging Drug Target in Migraine and Cluster Headache
Authors: Vollesen Anne Luise Haulund , Ashina Messoud
Published: May 2017

Here, we review the role of pituitary adenylate cyclase‐activating peptide‐38 (PACAP38) in migraine and cluster headache (CH). Mounting evidence implicates signaling molecule PACAP38 in the pathophysiology of migraine. Human provocation studies show PACAP38 induces migraine attacks in migraine patients without aura and marked and sustained dilation of extracerebral arteries. PACAP38 selectively targets the PAC1 receptor making this receptor a promising candidate for targeted migraine therapy. Randomized clinical trials are warranted to pursue this possible treatment pathway. PACAP38 provocation studies in CH could elucidate possible involvement of PACAP38 in CH pathophysiology and predict efficacy of PACAP38 antagonists in this primary headache.
Amylin
Authors: Hay Debbie L.
Published: May 2017

Amylin is a 37 amino acid peptide hormone that is closely related to calcitonin gene‐related peptide (CGRP). Amylin and CGRP share a receptor and are reported to have several similar biological actions. Given the important role of CGRP in migraine and intense efforts to develop drugs against this target, it is important to consider potential areas of overlap between the amylin and CGRP systems. This short review provides a brief introduction to amylin biology, the use of an amylin analog to treat diabetes, and consideration of whether amylin could have any role in headache disorders. Finally, this review informs readers about the AMY1 (amylin subtype 1) receptor, which is a dual receptor for amylin and CGRP and potentially plays a role in the bioactivity of both of these peptides.
Oxytocin and Migraine Headache
Authors: Tzabazis Alexander , Kori Shashi , Mechanic Jordan , Miller James , Pascual Conrado , Manering Neil , Carson Dean , Klukinov Michael , Spierings Egilius , Jacobs Daniel , Cuellar Jason , Frey William H. , Hanson Leah , Angst Martin , Yeomans David C.
Published: May 2017

This article reviews material presented at the 2016 Scottsdale Headache Symposium. This presentation provided scientific results and rationale for the use of intranasal oxytocin for the treatment of migraine headache. Results from preclinical experiments are reviewed, including in vitro experiments demonstrating that trigeminal ganglia neurons possess oxytocin receptors and are inhibited by oxytocin. Furthermore, most of these same neurons contain CGRP, the release of which is inhibited by oxytocin. Results are also presented which demonstrate that nasal oxytocin inhibits responses of trigeminal nucleus caudalis neurons to noxious stimulation using either noxious facial shock or nitroglycerin infusion. These studies led to testing the analgesic effect of intranasal oxytocin in episodic migraineurs—studies which did not meet their primary endpoint of pain relief at 2 h, but which were highly informative and led to additional rat studies wherein inflammation was found to dramatically upregulate the number of oxytocin receptors available on trigeminal neurons. This importance of inflammation was supported by a series of in vivo rat behavioral studies, which demonstrated a clear craniofacial analgesic effect when a pre‐existing inflammatory injury was present. The significance of inflammation was further solidified by a small single‐dose clinical study, which showed analgesic efficacy that was substantially stronger in chronic migraine patients that had not taken an anti‐inflammatory drug within 24 h of oxytocin dosing. A follow‐on open label study examining effects of one month of intranasal oxytocin dosing did show a reduction in pain, but a more impressive decrease in the frequency of headaches in both chronic and high frequency episodic migraineurs. This study led to a multicountry double blind, placebo controlled study studying whether, over 2 months of dosing, “as needed” dosing of intranasal oxytocin by chronic and high frequency migraineurs would reduce the frequency of their headaches compared to a 1‐month baseline period. This study failed to meet its primary endpoint, due to an extraordinarily high placebo rate in the country of most of the patients (Chile), but was also highly informative, showing strong results in other countries and strong post hoc indications of efficacy. The results provide a strong argument for further development of intranasal oxytocin for migraine prophylaxis.
EGFR gene mutation in gastrointestinal stromal tumours
Authors: Shi Shan‐Shan , Wu Nan , He Yan , Wei Xue , Xia Qiu‐Yuan , Wang Xuan , Ye Sheng‐Bin , Li Rui , Rao Qiu , Zhou Xiao‐Jun
Published: May 2017

Aims

The aim of this study was to evaluate the mutation status of epidermal growth factor receptor (EGFR) in gastrointestinal stromal tumours (GISTs) and its association with various clinicopathological variables, as well as to discuss further the effects of EGFR mutations on tumour formation and progression.

Methods and results

A well‐characterized cohort of 323 GISTs, obtained between 2010 and 2015 from the surgical pathology files of at the Department of Pathology of the Nanjing Jinling Hospital, was screened for mutations in exons 19 and 21 of the EGFR gene. Patient clinical data and clinicopathological features were collected if available in the medical records. Among the 323 primary GISTs, we identified three cases (0.93%) of EGFR mutations; these mutations never occurred together with KIT, PDGFRα, KRAS or BRAF mutations. In two cases, tumour cells exhibited spindle cell morphology and, in one case, epithelioid cell morphology. Additionally, the morphology and immunophenotype of these three cases did not show significant differences compared to common GISTs. The clinical results in summary were that two cases of EGFR‐mutated GISTs occurred in females and in the stomach. The mean age of EGFR‐mutated cases was 54.33 years, and the follow‐up data indicated that these tumours were low risk and exhibited low recurrence.

Conclusions

We first established that GISTs carrying EGFR mutation are relatively benign tumours. Although EGFR mutations were rarely present in GIST, EGFR seems to play a significant role in the development and progression of GIST.
Stratigraphic records of tsunamis along the Japan Sea, southwest Hokkaido, northern Japan
Authors: Kawakami Gentaro , Nishina Kenji , Kase Yoshihiro , Tajika Jun , Hayashi Keiichi , Hirose Wataru , Sagayama Tsumoru , Watanabe Tatsuya , Ishimaru Satoshi , Koshimizu Ken'ichi , Takahashi Ryo , Hirakawa Kazuomi
Published: May 2017

The stratigraphy of tsunami deposits along the Japan Sea, southwest Hokkaido, northern Japan, reveals tsunami recurrences in this particular area. Sandy tsunami deposits are preserved in small valley plains, whereas gravelly deposits of possible tsunami origin are identified in surficial soils covering a Holocene marine terrace and a slope talus. At least five horizons of tsunami events can be defined in the Okushiri Island, the youngest of which immediately overlies the Ko‐d tephra layer (1640 AD) and was likely formed by the historical Oshima‐Ohshima tsunami in 1741 AD. The four older tsunami deposits, dated using accelerator mass spectrometry 14C, were formed at around the 12th century, 1.5–1.6, 2.4–2.6, and 2.8–3.1 ka, respectively. Tsunami sand beds of the 1741 AD and circa 12th century events are recognized in the Hiyama District of Hokkaido Island, but the older tsunami deposits are missing. The deposits of these two tsunamis are found together at the same sites and distributed in regions where wave heights of the 1993 tsunami (Hokkaido Nansei‐oki earthquake, Mw = 7.7) were less than 3 m. Thus, the 12th century tsunami waves were possibly generated near the south of Okushiri Island, whereas the 1993 tsunami was generated towards the north of the island. The estimated recurrence intervals of paleotsunamis, 200–1100 years with an average of 500 years, likely represents the recurrence interval of large earthquakes which would have occurred along several active faults offshore of southwest Hokkaido.
Duplex of metamorphic units including ultramafic rocks in the central region of Tokunoshima, Southwest Japan
Authors: Ueda Shuro , Yamamoto Hiroshi , Terabayashi Masaru
Published: May 2017

Geological observations in the central part of Tokunoshima in the Amami Islands, Southwest Japan, reveal that discrete layers of serpentinite, dioritic gneiss, and amphibolite are intercalated into pelitic schist and these rock bodies form a northwest‐dipping tectonic stack. A subhorizontal psammitic schist layer overlies them. These rocks underwent ductile deformation that is denoted by penetrative foliation and mineral lineation. Microstructures of the sheared metamorphic rocks and serpentinite indicate top‐to‐the‐east, ‐southeast or ‐south (hanging‐wall up) displacements. The en echelon array of rock bodies is interpreted as a duplex with the psammitic schist layer on its top and the pelitic schist layer on its bottom. It is inferred that the serpentinite‐bearing duplex was formed due to the tectonic erosion and the subsequent accretionary growth operated in a Cretaceous or older subduction zone. Tokunoshima has been considered to belong to the Shimanto Belt. However, regional low‐pressure and high‐temperature type amphibolite‐facies metamorphism and related ductile deformation have not been recognized in the other areas of the Shimanto Belt. There is no metamorphic rock occurrence comparable to that of Tokunoshima in the neighboring islands. The metamorphic rocks in Tokunoshima can be correlated to any of low‐pressure/temperature type metamorphic regions in Kyushu.
Italian Scientists Abroad in Europe's Scientific Research Scenario: High skill migration as a resource for development in Italy
Authors: Sbalchiero Stefano , Tuzzi Arjuna
Published: May 2017

In recent years, the brain drain issue has gained such momentum that it has become necessary to adopt tools and methods to take a picture of a phenomenon that is, by its very nature, dynamic and changeable (Portes, ; Meyer, ; Ackers, 2005 Scott, ). This particular study focuses on clarifying the reasons why Italian scientists choose to look elsewhere for the best place to conduct their scientific research, and in what way their scientific experience abroad shapes the image of the Italian scientific system. A first exploratory analysis involving 83 in‐depth interviews with Italian scientists (mathematicians, engineers and physicists) working in Europe was conducted based on qualitative and quantitative analytical methods, and the content emerging from these interviews was used for a systematic mapping of the situation that provided the foundations for our preparation of a second tool – a questionnaire – that was subsequently used to conduct a much more broad‐based survey that involved 602 respondents. While our findings add complexity to existing theories on the brain drain and brain circulation, they also confirm the potential of highly skilled migration to improve the national development of Italian academic system.
Survey of practices around pharmaceutical company funding for continuing professional development among medical oncologists and trainees in Australia
Authors: Lee Yeh Chen , Kroon René , Koczwara Bogda , Haines Ian , Francis Kay , Millward Michael , Kefford Richard , Olver Ian , Mileshkin Linda
Published: May 2017

Background

The completion of continuing professional development (CPD) is mandatory for medical oncologists and trainees (MO&T). Pharmaceutical companies may fund some CPD activities, but there is increasing debate about the potential for conflicts of interest (COI).

Aim

To assess current practices around funding to attend CPD activities.

Methods

An electronic survey was distributed to Australian MO&T. The survey asked questions about current practices, institutional policies and perceptions about attending CPD funded by pharmaceutical companies. The design looked at comparing responses between MO&T as well as their understanding of and training around institutional and ethical process.

Results

A total of 157 of 653 (24%) responses was received, the majority from MO (76%). Most CPD activities attended by MO&T were self‐funded (53%), followed by funding from institutions (19%), pharmaceutical companies (16%) and salary award (16%). Most institutions allowed MO&T to receive CPD funding from professional organisations (104/157, 66%) or pharmaceutical companies (90/157, 57%). A minority of respondents (13/157, 8%) reported that the process to use pharmaceutical funds had been considered by an ethics committee. Although 103/157 (66%) had received pharmaceutical funding for CPD, most (109/157, 69%) reported never receiving training about potential COI. The lack of education was more noticeable among trainees (odds ratio (OR) 8.61, P = 0.02). MO&T acknowledged the potential bias towards a pharmaceutical product (P = 0.05) but believed there was adequate separation between themselves and pharmaceutical companies (P < 0.01).

Conclusion

Majority of CPD attended by MO&T is self‐funded. There is lack of clarity in institutional policies regarding external funding support for CPD activities. Formal education about potential COI is lacking.
Giant cell arteritis: beyond temporal artery biopsy and steroids
Authors: Ninan Jem V. , Lester Susan , Hill Catherine L.
Published: May 2017

Giant cell arteritis is the most common primary vasculitis of the elderly. The acute complications of untreated giant cell arteritis, such as vision loss or occasionally stroke, can be devastating. The diagnosis is, however, not altogether straightforward due to variable sensitivities of the temporal artery biopsy as a reference diagnostic test. In this review, we discuss the increasing role of imaging in the diagnosis of giant cell arteritis. Glucocorticoid treatment is the backbone of therapy, but it is associated with significant adverse effects. A less toxic alternative is required. Conventional and novel immunosuppressive agents have only demonstrated modest effects in a subgroup of steroid refractory Giant cell arteritis due to the different arms of the immune system at play. However, recently a study of interleukin‐6 blockade demonstrated benefits of giant cell arteritis. The current status of these immunosuppressive agents and novel therapies are also discussed in this review.
Role of telehealth in perioperative medicine for regional and rural patients in Queensland
Authors: Tam Alec , Leung Amy , O'Callaghan Cara , Fagermo Narelle
Published: May 2017

Background

Australians living in regional, rural and remote areas face a myriad of complexities resulting in a trend to poorer health outcomes. Telehealth is being utilised as an alternative mode of service delivery to overcome such barriers. However, there is limited published information concerning the use of telehealth in perioperative medicine.

Aims

To review the performance of the telehealth preoperative assessment service at Mater Hospital Brisbane to determine last‐minute cancellation rates secondary to medical reasons.

Methods

A retrospective chart audit of all patients referred to perioperative medicine telehealth consultation services was provided at Mater Hospital Brisbane.

Results

During a 1‐year period, 229 patients across eight surgical subspecialties were referred for telehealth assessment (85 females, 144 males) with a median age of 67 years. Patients lived a median distance of 1597 km from Brisbane. Of the 229 patients included in the study, 7 (3.1%) experienced last‐minute cancellations. From these data, the last‐minute cancellation rate due to medical reasons was 1.3%, which is consistent with the international average.

Conclusion

The Mater Hospital Perioperative Medicine Telehealth Programme is a means of providing comprehensive perioperative assessment to regional, rural and remote patients that result in reduced last‐minute surgical cancellations and surgery within or below the national recommended guidelines.
Effects of Na+ substitution Cs+ on the microstructure and thermal expansion behavior of ceramic derived from geopolymer
Authors: Yuan Jingkun , He Peigang , Jia Dechang , You Jinsong , Liu Xuzhao , Zhang Yao , Cai Delong , Yang Zhihua , Duan Xiaoming , Wang Shengjin , Zhou Yu
Published: May 2017

As part of a series of studies, effects of Na+ substitution on the thermal evolution of cesium‐based geopolymers on heating were studied. A series of sodium‐substituted cesium‐based geopolymers, Cs(1−x)NaxGPs (where x=0, 0.1, 0.2, 0.3, and 0.4), were prepared and treated at 1300°C for 2 hours to obtain the corresponding ceramic products. The thermal evolution process was disclosed by virtue of a variety of technical, including TG‐DTA, thermal shrinkage, XRD analysis, SEM, and TEM investigation. The results indicated that unheated Cs(1−x)NaxGPs was not completely amorphous after the substitution of Na+ and the crystallinity of Cs(1−x)NaxGPs gradually increased with the rise of sodium content. Meanwhile, the average particle sizes of Cs(1−x)NaxGPs also increased evidently with increases in sodium substitution. The final product after heat treatment mainly consisted of pollucite (CsAlSi2O6) and amorphous glass phase. The particle size of pollucite grain gradually decreased as more Cs+ were replaced maybe owing to the role of Na+ in the nucleation process of pollucite. Two forms of Na+ present in the final products: A small portion was present in the pollucite grains due to Na+ partial occupied the crystallographic sites of Cs+; and the rest were present in the amorphous glass phase among the pollucite grains. The average coefficient of thermal expansion (CTE) of resulting Cs(1−x)NaxGPs ceramics increased from 4.80×10‐6 K−1 (x=0) to 7.26×10−6 K−1 (x=0.4) with increases in sodium substitution, which could be due to the amorphous glass phase had a relatively higher CTE than that of pollucite.
Surface and grain‐boundary excess of ZnO‐doped SnO2 nanopowders by the selective lixiviation method
Authors: Gouvêa Douglas , do Rosário Deise C.C. , Caliman Lorena B.
Published: May 2017

The primary characteristic of nanopowders is the high surface area and consequently high fraction of atoms on the interfaces, which changes the energy of the system. The additive distribution in the nanopowder interfaces is a fundamental aspect to control the energy, particle size, and final properties of nanopowders. In this work, the surface excess was determined using a selective lixiviation method, where a low‐water‐soluble oxide, SnO2, was used as the matrix, and a high‐water‐soluble oxide, ZnO, was used as the additive. The X‐ray photoelectron spectroscopy (XPS) analysis confirmed that ZnO segregated on SnO2 surfaces. However, after acid lixiviation the same analysis showed an undetectable surface concentration of ZnO. The evaluation of the nanostructure change and surface composition enables us to calculate the heat of segregation for the grain boundary and surface and the interface energy reduction because of segregation. At low‐ZnO concentrations, the additive solubilizes in the bulk and promotes particle growth. However, the segregation to the grain boundary and surface determines the relative stability of each interface, which promotes hard agglomeration and particle size stabilization at intermediated ZnO amounts. At high‐ZnO concentrations, the surface segregation stabilizes the solid‐gas interface and decreases the agglomeration and final particle size.
Crack opening behavior in ceramic matrix composites
Authors: Sevener Kathleen M. , Tracy Jared M. , Chen Zhe , Kiser James D. , Daly Samantha
Published: May 2017

The evolution of matrix cracks in a melt‐infiltrated SiC/SiC ceramic matrix composite (CMC) under uniaxial tension was examined using scanning electron microscopy (SEM) combined with digital image correlation (DIC) and manual crack opening displacement (COD) measurements. CMC modeling and life prediction strongly depend a thorough understanding of when matrix cracks occur, the extent of cracking for given conditions (time‐temperature‐environment‐stress), and the interactions of matrix cracks with fibers and interfaces. In this work, strain relaxation due to matrix cracking, the relationship between CODs and applied stress, and damage evolution at stresses below the proportional limit were assessed. Direct experimental observation of strain relaxation adjacent to regions of matrix cracking is presented and discussed. Additionally, crack openings were found to increase linearly with increasing applied stress, and no crack was found to pass fully through the gage cross‐section. This calls into question the modeling assumption of through‐cracks for all loading conditions and fiber architectures, which can obscure oxidation mechanisms that are active in realistic cracking conditions. Finally, the combination of SEM with DIC is demonstrated throughout to be a powerful means for damage identification and quantification in CMCs at stresses well below the proportional limit.
Consensus statement of the International Summit on Intellectual Disability and Dementia related to end‐of‐life care in advanced dementia
Authors: McCallion Philip , Hogan Mary , Santos Flavia H , McCarron Mary , Service Kathryn , Stemp Sandy , Keller Seth , Fortea Juan , Bishop Kathleen , Watchman Karen , Janicki Matthew P ,   the Working Group of the International Summit on Intellectual Disability and Dementia
Published: May 2017

Background

Adults with intellectual disability are affected by dementia at equivalent and elevated rates, many surviving into advanced age. End of life care and support considerations come into play among these individuals when most are in the advanced stage of dementia.

Methods

A preliminary report summarizing available literature and making initial recommendations was developed by a workgroup, reviewed by all conference participants and then was finalized by the workgroup.

Results

The International Summit on Intellectual Disability and Dementia produced a report on End of life care in advanced dementia that provides a synthesis statement which encompasses defining the state of advanced dementia, proposes use of palliative care services (including hospice) and recommends special efforts for enabling advanced directives and advance care planning prior to the extensive progression of dementia. The Summit further recommended that when aiding adults with advanced dementia, the following be undertaken: integrative efforts between intellectual disability and palliative care providers, specialized training for carers on end of life care and supports, and involvement of adults with intellectual disability early on in their advance care planning.

Conclusions

The Consensus recommendations will ensure greater and more appropriate support at end of life for persons with intellectual disabilities and advanced dementia.
Increased prevalence of HCV and hepatic decompensation in adults with psoriasis: a population‐based study in the United Kingdom
Authors: Noe M.H. , Grewal S.K. , Shin D.B. , Ogdie A. , Takeshita J. , Gelfand J.M.
Published: May 2017

Background

The hepatitis C virus (HCV) is a major cause of global morbidity and mortality, with conflicting evidence regarding a possible association with psoriasis.

Objective

To determine the prevalence of HCV in psoriasis patients, compared to controls, and to determine the incidence of hepatic decompensation in HCV+ psoriasis patients compared to HCV+ controls.

Methods

Cross‐sectional and cohort studies were conducted in The Health Improvement Network (THIN).

Results

In fully adjusted models, a statistically significant increase in prevalence was seen in the adults with psoriasis (OR: 1.24, 95% CI 1.10–1.40). A “dose–response” of HCV prevalence with increasing psoriasis severity was not observed. HCV+ patients with psoriasis had a non‐statistically significant increased incidence of hepatic decompensation compared to HCV+ individuals without psoriasis (aHR: 1.58, 95% CI: 0.90–2.77). The risk was highest and statistically significant, in those with moderate‐to‐severe psoriasis (aHR: 21.51, 95% CI: 7.58–61.03).

Conclusions

These results demonstrate a higher prevalence of HCV in adults with psoriasis and a higher rate of hepatic decompensation in HCV+ individuals with moderate‐severe psoriasis.
Adverse events associated with discontinuation of the biologics/classic systemic treatments for moderate‐to‐severe plaque psoriasis: data from the Spanish Biologics Registry, Biobadaderm
Authors: Belinchón I. , Ramos J.M. , Carretero G. , Ferrándiz C. , Rivera R. , Daudén E. , De la Cueva‐Dobao P. , Gómez‐García F.J. , Herrera‐Ceballos E. , Sánchez‐Carazo J.L. , López‐Estebaranz J.L. , Alsina M. , Ferrán M. , Torrado R. , Carrascosa J.M. , Llamas‐Velasco M. , Ortiz P.L. , García‐Doval I. , Descalzo M.A. ,   The Biobadaderm Study Group
Published: May 2017

Background

Little is known about the adverse events (AEs) that lead to suspension of systemic treatments for psoriasis in clinical practice.

Objective

The study aimed to investigate AEs associated with discontinuation of systemic therapy in patients with psoriasis in a clinical setting (Biobadaderm).

Materials and methods

Multicentre, prospective, cohort study of patients with moderate‐to‐severe plaque psoriasis receiving systemic therapies from January 2008 to November 2015, in 12 hospitals in Spain. The incidence rate (IR) was used to compare biologics and classic systemic therapies.

Results

A total of 4218 courses of treatment were given to 1938 patients. A total of 447 (11%) treatments were discontinued due to AEs. The IR of AE associated with discontinuation of systemic therapies was 13 events/100 patient‐years (PY) (95% CI: 12.14–13.93), 9.34 events/100 PY (95% CI: 8.44–10.33) for biologics and 19.67 (95% CI: 17.9–21.6) events/100 PY for classics (P < 0.001). Of 810 discontinuation‐related AEs, 117 (14%) were serious. The highest IRs were for cyclosporine [49.18/100 PY (95% CI: 41.91–57.72)] and infliximab [26.52/100 PY (95% CI: 20.98–33.51). Ustekinumab presented the lowest IR (2.6/100 PY (95% CI: 1.83–3.69).

Limitations

Observational study with potential selection bias.

Conclusion

Biologic therapies are associated with a lower rate of discontinuation‐related AEs than are classic therapies in real clinical practice. Ustekinumab showed the lowest incidence.
The combined effects of temporal autocorrelation and the costs of plasticity on the evolution of plasticity
Authors: Siljestam M. , Östman Ö.
Published: May 2017

Adaptive phenotypic plasticity is an important source of intraspecific variation, and for many plastic traits, the costs or factors limiting plasticity seem cryptic. However, there are several different factors that may constrain the evolution of plasticity, but few models have considered costs and limiting factors simultaneously. Here we use a simulation model to investigate how the optimal level of plasticity in a population depends on a fixed maintenance fitness cost for plasticity or an incremental fitness cost for producing a plastic response in combination with environmental unpredictability (environmental fluctuation speed) limiting plasticity. Our model identifies two mechanisms that act, almost separately, to constrain the evolution of plasticity: (i) the fitness cost of plasticity scaled by the nonplastic environmental tolerance, and (ii) the environmental fluctuation speed scaled by the rate of phenotypic change. That is, the evolution of plasticity is constrained by the high cost of plasticity in combination with high tolerance for environmental variation, or fast environmental changes in combination with slow plastic response. Qualitatively similar results are found when maintenance and incremental fitness costs of plasticity are incorporated, although a larger degree of plasticity is selected for with an incremental cost. Our model highlights that it is important to consider direct fitness costs and phenotypic limitations in relation to nonplastic environmental tolerance and environmental fluctuations, respectively, to understand what constrains the evolution of phenotypic plasticity.
The evolution of a complex trait: cuticular hydrocarbons in ants evolve independent from phylogenetic constraints
Authors: Menzel F. , Schmitt T. , Blaimer B. B.
Published: May 2017

Cuticular hydrocarbons (CHCs) are ubiquitous and highly diverse in insects, serving as communication signal and waterproofing agent. Despite their vital function, the causes, mechanisms and constraints on CHC diversification are still poorly understood. Here, we investigated phylogenetic constraints on the evolution of CHC profiles, using a global data set of the species‐rich and chemically diverse ant genus Crematogaster. We decomposed CHC profiles into quantitative (relative abundances, chain length) and qualitative traits (presence/absence of CHC classes). A species‐level phylogeny was estimated using newly generated and previously published sequences from five nuclear markers. Moreover, we reconstructed a phylogeny for the chemically diverse Crematogaster levior species group using cytochrome oxidase I. Phylogenetic signal was measured for these traits on genus and clade level and within the chemically diverse C. levior group. For most quantitative CHC traits, phylogenetic signal was low and did not differ from random expectation. This was true on the level of genus, clade and species group, indicating that CHC traits are evolutionary labile. In contrast, the presence or absence of alkenes and alkadienes was highly conserved within the C. levior group. Hence, the presence or absence of biosynthetic pathways may be phylogenetically constrained, especially at lower taxonomic levels. Our study shows that CHC composition can evolve rapidly, allowing insects to quickly adapt their chemical profiles to external selection pressures, whereas the presence of biosynthetic pathways appears more constrained. However, our results stress the importance to consider the taxonomic level when investigating phylogenetic constraints.
Is Geriatric Medicine Possible in a Middle‐Income Country? The Case of Costa Rica
Authors: Morales‐Martínez Fernando
Published: May 2017

This article outlines the current and future‐projected demographic data, organization, networks for the care of older people, and perspectives in Costa Rica in relation to the challenges resulting from exponential growth of the older adult population, most notably those aged 80 and older. It includes consideration of the Norms of Integrated Care of the Older Adult of Costa Rica's national social security system and contributions from other public and private institutions. It also makes note of commentaries on the need for ever‐increasing efforts to manage the care of Costa Rica's burgeoning older adult population.
Selective Serotonin Reuptake Inhibitors as First‐Line Antidepressant Therapy for Perinatal Depression
Authors: Latendresse Gwen , Elmore Christina , Deneris Ann
Published: May 2017

One in 7 women experience depression during the prenatal and/or postpartum period. Nonpharmacologic approaches are known to be as effective as pharmacologic therapies for mild to moderate depression. However, for women who suffer from moderate to severe depression, antidepressant therapy may be the best option, in combination with nonpharmacologic approaches. Considering the substantial negative impact of untreated perinatal depression, providers of prenatal care need to be prepared to diagnose depression, prescribe first‐line antidepressants, and refer to other professionals. The purpose of this article is to assist providers to select the safest, most effective selective serotonin reuptake inhibitor (SSRI) as the first‐line antidepressant during pregnancy and lactation. Information about side effects, adverse effects, contraindications, and clinical considerations associated with the use of SSRIs is provided. A brief discussion of nonpharmacologic therapies is provided but is not the focus of this article.
Sonic hedgehog signalling mediates astrocyte crosstalk with neurons to confer neuroprotection
Authors: Ugbode Christopher I. , Smith Imogen , Whalley Benjamin J. , Hirst Warren D. , Rattray Marcus
Published: May 2017

Sonic hedgehog (SHH) is a glycoprotein associated with development that is also expressed in the adult CNS and released after brain injury. Since the SHH receptors patched homolog‐1 and Smoothened are highly expressed on astrocytes, we hypothesized that SHH regulates astrocyte function. Primary mouse cortical astrocytes derived from embryonic Swiss mouse cortices, were treated with two chemically distinct agonists of the SHH pathway, which caused astrocytes to elongate and proliferate. These changes are accompanied by decreases in the major astrocyte glutamate transporter‐1 and the astrocyte intermediate filament protein glial fibrillary acidic protein. Multisite electrophysiological recordings revealed that the SHH agonist, smoothened agonist suppressed neuronal firing in astrocyte‐neuron co‐cultures and this was abolished by the astrocyte metabolic inhibitor ethylfluoroacetate, revealing that SHH stimulation of metabolically active astrocytes influences neuronal firing. Using three‐dimensional co‐culture, MAP2 western blotting and immunohistochemistry, we show that SHH‐stimulated astrocytes protect neurons from kainate‐induced cell death. Altogether the results show that SHH regulation of astrocyte function represents an endogenous neuroprotective mechanism.

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Y5 receptor signalling counteracts the anorectic effects of PYY3‐36 in diet‐induced obese mice
Authors: Shi Y.‐C. , Ip C. K. , Reed F. , Sarruf D. A. , Wulff B. S. , Herzog H.
Published: May 2017

Peptide YY 3‐36 (PYY3‐36) is known as a critical satiety factor that reduces food intake both in rodents and humans. Although the anorexic effect of PYY3‐36 is assumed to be mediated mainly by the Y2 receptor, the involvement of other Y‐receptors in this process has never been conclusively resolved. Amongst them, the Y5 receptor (Y5R) is the most likely candidate to also be a target for PYY3‐36, which is considered to counteract the anorectic effects of Y2R activation. In the present study, we show that short‐term treatment of diet‐induced obese wild‐type (WT) and Y5R knockout mice (Y5KO) with PYY3‐36 leads to a significantly reduced food intake in both genotypes, which is more pronounced in Y5R KO mice. Interestingly, chronic PYY3‐36 infusion via minipumps to WT mice causes an increased cumulative food intake, which is associated with increased body weight gain. By contrast, lack of Y5R reversed this effect. Consistent with the observed increased body weight and fat mass in WT‐treated mice, glucose tolerance was also impaired by chronic PYY3‐36 treatment. Again, this was less affected in Y5KO mice, suggestive of a role of Y5R in the regulation of glucose homeostasis. Taken together, our data suggest that PYY3‐36 mediated signalling via Y5 receptors may counteract the anorectic effects that it mediates via the Y2 receptor (Y2R), consequently lowering bodyweight in the absence of Y5 signalling. These findings open the potential of combination therapy using PYY3‐36 and Y5R antagonists to enhance the food intake reducing effects of PYY3‐36.
PELP1: a key mediator of oestrogen signalling and actions in the brain
Authors: Thakkar R. , Sareddy G. R. , Zhang Q. , Wang R. , Vadlamudi R. K. , Brann D.
Published: May 2017

Proline‐, glutamic acid‐ and leucine‐rich protein 1 (PELP1) is an oestrogen receptor (ER) coregulator protein identified by our collaborative group. Work from our laboratory and others has shown that PELP1 is a scaffold protein that interacts with ERs and kinase signalling factors, as well as proteins involved in chromatin remodelling and DNA repair. Its role in mediating 17β‐oestradiol (E2) signalling and actions has been studied in detail in cancer cells, although only recently has attention turned to its role in the brain. In this review, we discuss the tissue, cellular and subcellular localisation of PELP1 in the brain. We also discuss recent evidence from PELP1 forebrain‐specific knockout mice demonstrating a critical role of PELP1 in mediating both extranuclear and nuclear ER signalling in the brain, as well as E2‐induced neuroprotection, anti‐inflammatory effects and regulation of cognitive function. Finally, the PELP1 interactome and unique gene network regulated by PELP1 in the brain is discussed, especially because it provides new insights into PELP1 biology, protein interactions and mechanisms of action in the brain. As a whole, the findings discussed in the present review indicate that PELP1 functions as a critical ER coregulator in the brain to mediate E2 signalling and actions.
Response inhibition and interference control: Effects of schizophrenia, genetic risk, and schizotypy
Authors: Ettinger Ulrich , Aichert Désirée S. , Wöstmann Nicola , Dehning Sandra , Riedel Michael , Kumari Veena
Published: May 2017

The ability to inhibit inappropriate responses and suppress irrelevant information is a core feature of executive control. In this study, we provide a detailed analysis of prepotent response inhibition and interference in patients with schizophrenia. To further test the role of genetic factors and subclinical schizophrenia‐like traits, we additionally studied clinically unaffected, first‐degree relatives of schizophrenia patients and assessed dimensions of schizotypy in both relatives and healthy controls. Inhibition and interference control were assessed using a battery comprising the antisaccade, Stroop, stop signal, go/no‐go, flanker, and Simon tasks. Schizophrenia patients differed from both relatives and controls in making more errors on the antisaccade task and having longer response times on the Stroop task, especially the incongruent condition. Patients also had general, that is, condition independent, increases in reaction times on the go/no‐go and flanker tasks and made more errors on the flanker and Simon tasks, suggesting general performance impairments independent of inhibitory demand. Relatives were characterized by hypometric antisaccade amplitude gain despite normal prosaccades, suggesting a selective deficit in non‐standard sensorimotor transformations. Schizotypy was correlated with inhibitory performance across a number of tasks in both relatives and controls. Generally, these effects were independent of verbal intelligence levels. Overall, the findings point to rather selective impairments of inhibitory control in the schizophrenia spectrum and confirm a previously observed deficit in antisaccade spatial accuracy as an endophenotype of schizophrenia.
Deletion of Sarm1 gene is neuroprotective in two models of peripheral neuropathy
Authors: Turkiew Elliot , Falconer Debbie , Reed Nicole , Höke Ahmet
Published: May 2017

Distal axon degeneration seen in many peripheral neuropathies is likely to share common molecular mechanisms with Wallerian degeneration. Although several studies in mouse models of peripheral neuropathy showed prevention of axon degeneration in the slow Wallerian degeneration (Wlds) mouse, the role of a recently identified player in Wallerian degeneration, Sarm1, has not been explored extensively. In this study, we show that mice lacking the Sarm1 gene are resistant to distal axonal degeneration in a model of chemotherapy induced peripheral neuropathy caused by paclitaxel and a model of high fat diet induced putative metabolic neuropathy. This study extends the role of Sarm1 to axon degeneration seen in peripheral neuropathies and identifies it as a likely target for therapeutic development.
Benefactors and Beneficiaries? Disability and Care to Others
Authors: Shandra Carrie L. , Penner Anna
Published: May 2017

Individuals with disabilities often have limitations that require care from others to increase functioning and facilitate activities of daily living. Despite these care‐receiving needs, evidence suggests people with disabilities are also care givers. This study uses the 2008–2015 American Time Use Survey to examine the association between the presence of sensory, mental or cognitive, physical, or multiple limitations and the likelihood and intensity of time spent in primary child care, secondary child care, adult care, care of nonhouseholders, and support care (housework). Net of socioeconomic characteristics, the authors do not observe consistent differences in predicted child care time by disability status, although men with disabilities spend less time in care to adults and nonhouseholders. The largest difference in predicted care time by disability status occurs in support care. Overall, the results challenge the traditional focus on people with disabilities as only beneficiaries of care to document their role as benefactors.