bluuebunny/crossref_metadata_2025 huggingface dataset:
Case series of docetaxel-induced dorsal hand–foot syndrome
Authors: Patel Jolly , Ringley J. Tanner , Moore Donald C.
Published: May 2018

Palmar–plantar erythrodysesthesia, also known as hand–foot syndrome (HFS), is a well-known dermatologic adverse event that can occur with a variety of cytotoxic chemotherapies including fluoropyrimidines, cytarabine, liposomal doxorubicin, and taxanes. HFS often presents as painful erythemas and desquamation of the skin involving the palms of the hands and the soles of the feet. Three cases are presented of patients with breast cancer who received multiagent chemotherapy regimens containing docetaxel that developed an atypical presentation of HFS on the dorsal aspect of the hands and feet. All patients received supportive care to manage the symptoms of their dermatologic toxicity. Dorsal HFS improved with supportive care or dose reduction and resolved following completion of the docetaxel-based chemotherapy. Based on the temporal relationship of the event and previous reports, we found that docetaxel was the probable offending agent.
Morphological changes and myocardial function assessed by traditional and novel echocardiographic methods in preadolescent athlete’s heart
Authors: Bjerring Anders W , Landgraff Hege EW , Leirstein Svein , Aaeng Anette , Ansari Hamza Z , Saberniak Jørg , Murbræch Klaus , Bruun Henrik , Stokke Thomas M , Haugaa Kristina H , Hallén Jostein , Edvardsen Thor , Sarvari Sebastian I
Published: May 2018

Background

Athlete’s heart is a term used to describe the morphological and functional changes in the hearts of athletes. Recent studies suggest that these changes may occur even in preadolescent athletes. This study aims to improve our understanding of the changes occurring in the preadolescent athlete’s heart.

Design and methods

Cardiac morphology and function in 76 preadolescent cross-country skiers (aged 12.1 ± 0.2 years) were compared with 25 age-matched non-competing preadolescents. Echocardiography was performed in all subjects, including 2D speckle-tracking strain echocardiography and 3D echocardiography. All participants underwent cardiopulmonary exercise testing to assess oxygen uptake and exercise capacity.

Results

Athletes had greater indexed VO2 max (62 ± 7 vs. 44 ± 5 mL/kg per min, p < 0.001), indexed left ventricular end-diastolic volume (79 ± 7 vs. 68 ± 7 mL/m2, p < 0.001), left ventricular mass (69 ± 12 vs. 57 ± 13 g/m2, p < 0.001), indexed right ventricular basal diameter (28.3 ± 3.0 vs. 25.4 ± 3.5 mm/m2, p < 0.001) and right atrial area (10.6 ± 1.4 vs. 9.7 ± 1.2 cm2/m2, p < 0.01). There was no difference in left ventricular ejection fraction, global longitudinal strain, and global circumferential strain and right ventricular fractional area change between the groups. Controls had higher right ventricular global longitudinal strain (−28.1 ± 3.5 vs. −31.1 ± 3.3%, p < 0.01). VO2 max was highly correlated to left ventricular end-diastolic volume ( r = 0.76, p < 0.001).

Conclusion

Athletes had greater left ventricular mass and greater left and right ventricular chamber dimensions compared with controls, while left ventricular function did not differ. Interestingly, right ventricular deformation was significantly lower compared with controls. This supports the notion that there is physiological, adaptive remodelling in preadolescent athlete’s heart.
Treatment of homozygous familial hypercholesterolaemia in paediatric patients: A monocentric experience
Authors: Buonuomo Paola S , Macchiaiolo Marina , Leone Giovanna , Valente Paola , Mastrogiorgio Gerarda , Gnazzo Maria , Rana Ippolita , Gonfiantini Michaela V , Gagliardi Maria G , Romano Francesca , Bartuli Andrea
Published: May 2018

Background

Homozygous familial hypercholesterolaemia is a rare life-threatening disease characterized by markedly elevated low-density lipoprotein cholesterol (LDL-C) concentrations and accelerated atherosclerosis. The presence of double gene defects in the LDL-Receptor, either the same defect (homozygous) or two different LDL-raising mutations (compound heterozygotes) or other variants, identify the homozygous phenotype (HopFH). Apheresis is a procedure in which plasma is separated from red blood cells before the physical removal of LDL-C or the LDL-C is directly removed from whole blood. It is currently the treatment of choice for patients with HopFH whose LDL-C levels are not able to be reduced to target levels with conventional lipid-lowering drug therapy.

Design

The aim of this study is to report a cohort of six paediatric patients and to evaluate the long term efficacy of combined medical therapy and LDL-apheresis on LDL-C reduction.

Methods

We collected data from six children with confirmed diagnosis of HopFH (two females and four males; age range at diagnosis 3–8 years, mean 6 ± 1 years) from a single clinical hospital in Italy from 2007 to 2017.

Results

Clinical manifestations and outcomes may greatly vary in children with HopFH. Medical therapy and LDL-apheresis for the severe form should be started promptly in order to prevent cardiovascular disease.

Conclusions

Lipoprotein apheresis is a very important tool in managing patients with HopFH at high risk of cardiovascular disease. Based on our experience and the literature data, the method is feasible in very young children, efficient regarding biological results and cardiac events, and safe with minor side-effects and technical problems. We advise treating homozygous and compound heterozygous children as soon as possible.
End-of-life decision making by family caregivers of persons with advanced dementia: A literature review of decision aids
Authors: Xie Bo , Berkley Amy S , Kwak Jung , Fleischmann Kenneth R , Champion Jane Dimmitt , Koltai Kolina S
Published: May 2018

Objectives:

To investigate existing knowledge in the literature about end-of-life decision making by family caregivers of persons with dementia, focusing on decision aids for caregivers of persons with advanced dementia, and to identify gaps in the literature that can guide future research.

Methods:

A literature review through systematic searches in PubMed, CINAHL Plus with Full Text, and PsycINFO was conducted in February 2018; publications with full text in English and published in the past 10 years were selected in multiple steps.

Results:

The final sample included five decision aids with predominantly Caucasian participants; three of them had control groups, and three used audiovisual technology in presenting the intervention materials. No other technology was used in any intervention. Existing interventions lacked tailoring of information to caregivers’ preferences for different types and amounts of information necessary to make decisions consistent with patients’ values.

Conclusion:

Research is needed in exploring the use of technology in decision aids that could provide tailored information to facilitate caregivers’ decision making. More diverse samples are needed.
Intellectual disability in patients with epilepsy with eyelid myoclonias
Authors: Arvio Maria , Sauna-aho Oili , Nyrke Timo , Bjelogrlic-Laakso Nina
Published: May 2018

We describe here the clinical outcome of four women with epilepsy with eyelid myoclonia (aged 21–53 years). All patients had an uneventful early history, normal physical growth and appearance and no comorbid sensory or motor disability and normal brain magnetic resonance imaging finding. Two women were moderately and one mildly intellectually disabled and one showed a low-average intelligence. The overall well-being of the patients was hampered by psychiatric or various somatic comorbidities and related psychosocial problems. The three women with an intellectual disability had been treated with narrow-spectrum antiepileptic drugs and one also with vigabatrin during childhood and adolescence. The patient with a low-average intelligence had been on broad-spectrum antiepileptic medication (i.e. valproate and ethosuximide) since the epilepsy diagnosis but she has had compliance problems. Based on these cases, the cognitive deficits in patients with epilepsy with eyelid myoclonia may occur more commonly than what has been thought hitherto. We discuss the role of narrow-spectrum antiepileptic drugs as a contributing factor to poor seizure control and an impaired intelligence.
Multiple spontaneous hemorrhages after commencing warfarin therapy
Authors: Akuzawa Nobuhiro , Kurabayashi Masahiko
Published: May 2018

A 94 year-old Japanese woman with renal dysfunction was admitted to our hospital for congestive heart failure caused by atrial fibrillation with rapid ventricular response. Considering the risk of stroke, warfarin was commenced. However, she developed shock following brachial and retroperitoneal hemorrhage 4 days after starting warfarin despite not being over-anticoagulated. She recovered after receiving blood transfusion and intravenous vitamin K2. Bleeding during warfarin administration occurs more frequently in older individuals with lower glomerular filtration rates, especially within the first 30 days of warfarin treatment. Physicians should therefore check for unexpected bleeding after commencing warfarin and be prepared to reverse anticoagulation.
Laparoscopic Harvesting of Omental Flaps for Breast Reconstruction—A Review of the Literature and Outcome Analysis
Authors: Shash Hani , Al-halabi Becher , Aldekhayel Salah , Dionisopoulos Tassos
Published: May 2018

Background:

Evidence on the use of omental flaps for breast reconstruction in patients with breast cancer is lacking, and no published reviews report an outcome-based assessment of such flap. This review explores available data and evidence for change in complication rates following the shift toward laparoscopic harvesting.

Methods:

We searched the databases Excerpta Medica database, MEDLINE, and PubMed from inception until December 2015 using search terms “omental flaps“ and “breast reconstruction.” Data extracted were patient characteristics, technique used, and outcome measures reported and were then analyzed based on the technique of harvesting.

Results:

Twenty-two articles reporting 651 patients who underwent mastectomies and breast-conserving surgeries were included in this review. Most flaps, 537 (82.5%), were harvested by laparoscopy, and 626 (96.2%) of the flaps were pedicle flaps. The mean age was 47.7 years (standard deviation: 4.29), and mean follow-up was 38.1 months. There were 88 reported complications among 562 patients in 16 reports. The rate of any complication was calculated to be 15.0%, with a higher rate (29.1%) occurring with the open technique in comparison to laparoscopy (12.6%). The commonest complications were postoperative infection and breast firmness each reported in 2.22%. Most authors reported advantages of malleability and excellent aesthetic outcomes and disadvantages in terms of inability to estimate the volume of the flap and variability in size.

Conclusion:

Omentum use is safe and has advantages in breast reconstruction where other options are limited including a natural feeling and minimal donor site morbidity if harvested laparoscopically.
Can Weakness in End-Range Plantar Flexion After Achilles Tendon Repair Be Prevented?
Authors: Orishimo Karl F. , Schwartz-Balle Sidse , Tyler Timothy F. , McHugh Malachy P. , Bedford Benjamin B. , Lee Steven J. , Nicholas Stephen J.
Published: May 2018

Background:

Disproportionate end-range plantar flexion weakness, decreased passive stiffness, and inability to perform a heel rise on a decline after Achilles tendon repair are thought to reflect increased tendon compliance or tendon lengthening. Since this was first noted, we have performed stronger repairs and avoided stretching into dorsiflexion for the first 12 weeks after surgery.

Hypothesis:

Using stronger repairs and avoiding stretching into dorsiflexion would eliminate end-range plantar flexion weakness and normalize passive stiffness.

Study Design:

Case series; Level of evidence, 4.

Methods:

Achilles repairs with epitendinous augmentation were performed on 18 patients. Plantar flexion torque, dorsiflexion range of motion (ROM), passive joint stiffness, and standing single-legged heel rise on a decline were assessed at 43 ± 24 months after surgery (range, 9 months to 8 years). Maximum isometric plantar flexion torque was measured at 20° and 10° of dorsiflexion, neutral position, and 10° and 20° of plantar flexion. Passive dorsiflexion ROM was measured with a goniometer. Passive joint stiffness was computed from the increase in passive torque from 10° to 20° of dorsiflexion. Tendon thickness was measured by use of digital calipers. Plantar flexion electromyographic (EMG) data were recorded during strength and functional tests. Analysis of variance and chi-square tests were used to assess weakness and function.

Results:

Marked weakness was evident on the involved side at 20° of plantar flexion (deficit, 26% ± 18%; P < .001), with no weakness at 20° of dorsiflexion (deficit, 6% ± 17%; P = .390). Dorsiflexion ROM was decreased 5.5° ± 8° ( P = .015), and tendon width was 8 ± 3 mm greater on the involved side ( P < .001). Passive joint stiffness was similar between the involved and noninvolved sides. Only 2 of 18 patients could perform a decline heel rise on the involved side compared with 18 of 18 on the noninvolved side ( P = .01). No difference in EMG amplitude was found between the involved and noninvolved sides during the strength or heel rise tests.

Conclusion:

The use of stronger repair techniques and attempts to limit tendon elongation by avoiding dorsiflexion stretching did not eliminate weakness in end-range plantar flexion. EMG data confirmed that end-range weakness was not due to neural inhibition. Physiological changes that alter the force transmission capability of the healing tendon may be responsible for this continued impairment. This weakness has implications for high-demand jumping and sprinting after Achilles tendon repair.
A Global Overview of the Geographical Distribution of Dentists: A Scoping Review
Authors: Gabriel M. , Cayetano M.H. , Galante M.L. , Carrer F.C. , Dussault G. , Araujo M.E.
Published: May 2018

The objective of this study was to identify and analyze the geographic distribution of dentists, in the global context, through available scientific evidence, highlighting the following aspects: 1) the determinants of the geographic distribution of dentists, 2) corrective intervention implemented, and 3) their monitoring and evaluation. A scoping review of the published and gray literature was carried out in scientific databases and in relevant websites. We used an adaptation of a World Health Organization framework to study the distribution of human resources in health to analyze selected publications. After applying the eligibility criteria, 53 publications were included in the review; 10 related to the determinants of geographical distribution, 5 to interventions implemented, and 38 to the monitoring and evaluation process. More studies are needed to identify local determinants of the geographical distribution of dentists and to define adapted intervention strategies to make it more equitable.

Knowledge Transfer Statement: The geographic inequality of dentists is a problem for health systems because it has a direct impact on access to services and the oral health conditions of a population. Our study was based on a theoretical conceptual framework formulated in 3 components: 1) determinants of the geographical distribution, 2) strategies implemented to correct the problem, and 3) monitoring and evaluation. It can assist in designing oral health policy and guide decisions by policy makers.
Sleep-Disordered Breathing Is Associated with Reduced Mandibular Cortical Width in Children
Authors: Eimar H. , Al-Saleh M.A.Q. , Cortes A.R.G. , Gozal D. , Graf D. , Flores-Mir C.
Published: May 2018

Introduction:

Evidence from the adult population suggests that sleep-disordered breathing (SDB) (i.e., obstructive sleep apnea [OSA]) is negatively associated with bone mineral density. Whether a similar association exists in children with SDB has not been investigated. Using the mandibular cortical width (MCW) as a proxy for skeletal bone density, we investigated if children at risk of SDB or diagnosed with OSA have a reduced mandibular cortical width compared to children without SDB.

Methods:

Two retrospective cross-sectional studies were performed. The first study included comparison of MCW between 24 children with polysomnographically (PSG) diagnosed OSA and 72 age- and sex-matched control children. The second study included a cohort of children in which SDB was suggested by the Pediatric Sleep Questionnaire (PSQ) ( n = 101). MCW was measured from panoramic radiographs.

Results:

Multiple-predictors regression analysis from the first study indicated that in children with a severe form of SDB, as induced by OSA severity, there was a negative association with MCW (β = –0.290, P = 0.049). Moreover, PSG-diagnosed OSA children had thinner MCW (2.9. ± 0.6mm) compared to healthy children (3.5 ± 0.6 mm; P = 0.002). These findings were further supported by the second study illustrating that PSQ total scores were negatively associated with MCW (β = –0.391, P < 0.001).

Conclusions:

Findings suggest that children at risk for or diagnosed with SDB exhibit reduced mandibular cortical width that purportedly may reflect alterations in bone homeostasis.

Knowledge Transfer Statement:

We report that sleep-disordered breathing (including its severe form, obstructive sleep apnea) in children is associated with reduced mandibular cortical width. This association might be a direct consequence of reduced bone health to sleep-disordered breathing or a reflection that reduced bone formation underlies the development of sleep-disordered breathing. Our findings suggest that mandibular cortical width can be used as an adjunct diagnostic parameter for the diagnosis of sleep-disordered breathing.
Thyroid Cancer and Iodine Deficiency Status: A 10‐Year Review at a Single Cancer Center in Tanzania
Authors: Sakafu Lulu L. , Mselle Teddy F. , Mwaiselage Julius D. , Maunda Khamza K. , Eddin Bouyoucef S. , Zafereo Mark E.
Published: May 2018

Objective

To highlight the magnitude and distribution of thyroid cancer at the largest cancer center in Tanzania and to correlate patient region of residence with regions of dietary iodine adequacy and deficiency in the country.

Study Design

A retrospective cross‐sectional chart review to characterize patients with thyroid cancer and regions of residence.

Setting

Ocean Road Cancer Institute (ORCI), the largest cancer center in Tanzania.

Subjects and Methods

Subjects had histologically confirmed thyroid cancer and no history of cancer treatment. Between January 2006 and April 2016, the cases of 139 consecutive patients with thyroid cancer at ORCI were retrospectively reviewed. Patients were grouped into those from iodine‐adequate and iodine‐deficient regions, based on the Tanzania demographic and health survey.

Results

Patients’ median age was 47 years (range, 17‐73 years), and the male:female ratio was 1:5. The number of people with thyroid cancer seen at ORCI increased steadily during the study period, with no significant difference between papillary (46%) and follicular (45%) diagnoses. Nonpapillary cancers occurred more frequently among males and patients ≥45 years of age, but these did not reach statistical significance. Seventy‐five percent of all thyroid cancers were from areas of iodine deficiency, and this was similar in papillary and follicular cancer subtypes.

Conclusion

The incidence of differentiated thyroid cancer is increasing at the largest cancer center in Tanzania, whereby papillary and follicular subtypes were significantly higher in regions with long‐standing dietary iodine deficiency.
Easy as A-B-C: Data-Based Guidelines for Implementing a Multitiered System of Supports Into Rural Schools
Authors: Pierce Corey D. , Mueller Tracy Gershwin
Published: May 2018

The challenges of working within rural schools can impact successful implementation of a multitiered system of supports (MTSS). Although special education and general education teachers’ responsibilities within a MTSS framework have been addressed through a myriad of school districts across the nation, rural districts face unique challenges that can impact successful MTSS implementation. Some of these rural challenges include, but are not limited to, teacher preparation and training, recruitment and retention, limited flexibility of teacher time, and inadequate access to material and space resources. This article addresses critical issues related to successful rural implementation of a MTSS, including the presentation of three data-based strategies rural districts can employ, referred to as the rural A-B-C’s: (a) approach academic and behavior instruction simultaneously, (b) be creative with data opportunities, and (c) collaborate with purpose. Case study application and tables are provided for ease of implementation.
Risk-adapted treatment of acute promyelocytic leukemia: results from the International Consortium for Childhood APL
Authors: Testi Anna Maria , Pession Andrea , Diverio Daniela , Grimwade David , Gibson Brenda , de Azevedo Amilcar Cardoso , Moran Lorena , Leverger Guy , Elitzur Sarah , Hasle Henrik , ten Bosch Jutte van der Werff , Smith Owen , De Rosa Marisa , Piciocchi Alfonso , Lo Coco Francesco , Foà Robin , Locatelli Franco , Kaspers Gertjan J. L.
Published: May 2018

Key Points

Risk-adapted therapy allowed achieving remarkable cure rates in an international trial on childhood APL. Reduction of the anthracycline cumulative dose coupled with ATRA extended use does not compromise the outcome of children with APL.
Inhibition of ATR acutely sensitizes acute myeloid leukemia cells to nucleoside analogs that target ribonucleotide reductase
Authors: Fordham Sarah E. , Blair Helen J. , Elstob Claire J. , Plummer Ruth , Drew Yvette , Curtin Nicola J. , Heidenreich Olaf , Pal Deepali , Jamieson David , Park Catherine , Pollard John , Fields Scott , Milne Paul , Jackson Graham H. , Marr Helen J. , Menne Tobias , Jones Gail L. , Allan James M.
Published: May 2018

Key Points

Loss of ATR signaling is cytotoxic to AML cells in combination with gemcitabine and hydroxyurea via the induction of replication stress. A small molecule inhibitor of ATR in combination with gemcitabine completely eradicates AML in an orthotopic xenograft mouse model.
Effect of canagliflozin on left ventricular diastolic function in patients with type 2 diabetes
Authors: Matsutani Daisuke , Sakamoto Masaya , Kayama Yosuke , Takeda Norihiko , Horiuchi Ryuzo , Utsunomiya Kazunori
Published: May 2018

Background

Type 2 diabetes mellitus (T2DM) greatly increases the risks of cardiovascular disease and heart failure. In particular, left ventricular diastolic dysfunction that develops from the early stages of T2DM is an important factor in the onset and exacerbation of heart failure. The effect of sodium-glucose cotransporter 2 inhibitors on left ventricular diastolic function has not been elucidated. We have performed the first prospective study on the effects of canagliflozin on left ventricular diastolic function in T2DM.

Methods

This study was performed to evaluate the effects of additional treatment with canagliflozin for 3 months on left ventricular diastolic function in patients with T2DM. A total of 38 patients with T2DM were consecutively recruited for this study. Left ventricular diastolic function was assessed by echocardiography. The primary study outcome was a change in the septal E/e′ as a parameter of left ventricular diastolic function.

Results

A total of 37 patients (25 males and 12 females) were included in the analysis. Mean age of participants was 64.2 ± 8.1 years (mean ± SD), mean duration of diabetes was 13.5 ± 8.1 years, and mean HbA1c was 7.9 ± 0.7%. Of the participants, 86.5% had hypertension, 100% had dyslipidemia, and 32.4% had cardiovascular disease. Canagliflozin significantly improved left ventricular diastolic function (septal E/e′ ratio 13.7 ± 3.5–12.1 ± 2.8, p = 0.001). Furthermore, among the various parameters that changed through the administration of canagliflozin, only changes in hemoglobin significantly correlated with changes in the septal E/e′ ratio (p = 0.002). In multiple regression analysis, changes in hemoglobin were also revealed to be an independent predictive factor for changes in the septal E/e′ ratio.

Conclusions

This study showed for the first time that canagliflozin could improve left ventricular diastolic function within 3 months in patients with T2DM. The benefit was especially apparent in patients with substantially improved hemoglobin values.

Trial registration UMIN Clinical Trials Registry UMIN000028141
An observational cohort study of the use of five-grass-pollen extract sublingual immunotherapy during the 2015 pollen season in France
Authors: Blin Patrick , Demoly Pascal , Drouet Martine , Falissard Bruno , Lignot-Maleyran Séverine , Maizi Hélène , Lorrain Simon , Lassalle Régis , Droz-Perroteau Cécile , Moore Nicholas , Molimard Mathieu
Published: May 2018

Background

Allergic rhinitis affects around one quarter of the Western European population. Prophylactic allergen immunotherapy may be useful to reduce the risk of acute symptomatic attacks (hayfever). A five-grass pollen extract sublingual immunotherapy (5GPE-SLIT) has been developed for the treatment of allergic rhinitis to grass pollen. The objective of this study was to describe real-world treatment patterns with 5GPE-SLIT in France with respect to the prescribing information.

Methods

This prospective cohort study was conducted by 90 community and hospital allergists. Adults and children (> 5 years old) starting a first treatment with 5GPE-SLIT prior to the 2015 pollen season were eligible. Data was collected at the inclusion visit and at the end of the pollen season. The primary outcome variable was compatibility of 5GPE-SLIT prescription with the prescribing information. This was determined with respect to four variables: (1) interval between 5GPE-SLIT initiation and onset of the pollen season ≥ 3 months, (2) age of patient ≥ 5 years, (3) intermittent symptoms or mild symptom severity (4) confirmatory diagnostic test. At study end, symptoms reported during the pollen season and any modifications to treatment or adverse events were documented.

Results

280 adults and 203 children were enrolled. The prescribing information was respected for 82.5% of adults and 86.7% of children. A skin test was performed for all patients. 5GPE-SLIT was started 3–5 months before the pollen season for 85.3%. Treatment was discontinued before the start of the pollen season in 11.0% of patients overall, generally because of an adverse event (78.8% of discontinuations). The mean duration of treatment was 5.2 months in adults and 5.6 months in children. At the end of follow-up, symptoms during the pollen season were intermittent for 75.0% of adults and 85.7% of children, and severity was mild for 61.8 and 66.0% respectively. During 5GPE-SLIT, the following symptoms reported during the previous year were not reported again in > 50% of patients: nasal congestion, rhinorrhoea, repeated sneezing, conjunctivitis and nasal pruritus.

Conclusions

5GPE-SLIT use was generally consistent with prescribing recommendations and was associated with an improvement of AR severity, with resolution of the principal AR symptoms in around half the patients treated.

Trial registration EUPAS9358. Registered 13 May 2015. Not prospectively registered. http://www.encepp.eu/encepp/viewResource.htm?id=16229
A regularized approach for estimation of a composite focal mechanism from a set of microearthquakes
Authors: Zhang Hongliang , Eaton David W.
Published: May 2018

We have developed a novel regularized approach to estimate a composite focal mechanism for microseismic events that share a similar source mechanism. The method operates by minimizing the weighted misfits of the SH/P amplitude ratios (in absolute sense and logarithmic scale) and P-wave polarities, using a regularization parameter determined from the trade-off curve for these values. This approach overcomes the low signal-to-noise ratio (S/N) and single-event azimuthal gaps that may otherwise limit the effectiveness of sparse surface arrays. Compared with focal mechanisms derived from P-wave polarity or amplitude-based methods, our regularized approach reduces the multiplicity of solutions and avoids the use of signed amplitude ratios, which may be ambiguous for data with low S/N. We apply our method to a set of 13 microseismic events recorded during hydraulic-fracture stimulation of the Marcellus Shale in West Virginia and Pennsylvania, USA, yielding a strike-slip focal mechanism accompanied by a minor normal component. Our solution is similar to previously reported focal mechanisms in this area. Jackknife analysis, which tests stability of the inversion based on random sampling of the observation, indicates 95% confidence intervals of 1° and 2°, respectively, for the plunge and azimuth of the P and T axes. By analyzing the event subsets, outliers are identified and the assumption of a single dominant focal mechanism is validated. Numerical modeling demonstrates that our approach is robust in the presence of variations of up to 0°–10° and 0°–35°, respectively, for the plunge and azimuth of P and T axes of the focal mechanisms of these events. Sensitivity analysis using synthetic data also indicates that the algorithm is tolerant to mispicks as well as errors in polarity and amplitude ratio. In the presence of some dissimilar focal mechanisms, the dominant focal mechanism can be reliably estimated if at least 70% of the events have similar source mechanisms.
Failure to tackle suicide inequalities across Europe
Authors: Das-Munshi Jayati , Thornicroft Graham
Published: May 2018

In this issue, Lorant et al. confirm a social gradient in risk of suicide, across 15 European countries, over a period of marked social change. Understanding contextual and life-course factors, and acknowledging under-funding for mental health and failures to implement national mental health policies, may provide the reasons for these disparities.

Declaration of interest

None.
Investigator Disclosure and Advanced Cancer Patient Understanding of Informed Consent and Prognosis in Phase I Clinical Trials
Authors: Hlubocky Fay J. , Kass Nancy E. , Roter Debra , Larson Susan , Wroblewski Kristen E. , Sugarman Jeremy , Daugherty Christopher K.
Published: May 2018

Purpose:

Advanced cancer patients (ACPs) who participate in phase I clinical trials often report a less-than-ideal understanding of the required elements of informed consent (IC) and unrealistic expectations for anticancer benefit and prognosis. We examined phase I clinical trial enrollment discussions and their associations with subsequent ACP understanding.

Methods:

Clinical encounters about enrollment in phase I trials between 101 ACPs and 29 oncologists (principal investigators [PIs] and fellows) at three US academic medical institutions were recorded. The Roter Interaction Analysis System was used for analysis. ACPs completed follow-up questionnaires to assess IC recall.

Results:

PIs disclosed the following phase I IC elements to ACPs in encounters: trial purpose in 40%; specific physical risks in 60%; potential specific medical benefits gained by trial participation (eg, disease stabilization) in 48.2%; and alternatives to phase I trial participation in 47.1%, with 1.1% of encounters containing palliative and 2.3% hospice information. PIs provided ACP-specific prognoses in 29.0% of encounters but used precise terms of death in only 4.7% and terminal in 1.2%. A significant association existed between PI disclosure of the trial purpose as dosage/toxicity, and ACPs subsequently correctly recalled trial purpose versus PIs who did not disclose it (85% v 13%; P < .05).

Conclusion:

Many oncologists provide incomplete disclosures about phase I trials to ACPs. When disclosure of certain elements of IC occurs, it seems to be associated with better recall, especially with regard to the research purpose of phase I trials.
Organ Donation After Circulatory Death: Ethical Issues and International Practices
Authors: Jericho Barbara G.
Published: May 2018

Donation after circulatory death (DCD) is an increasingly utilized practice that can contribute to reducing the difference between the supply of organs and the demand for organs for transplantation. As the number of transplanted organs from DCD donors continues to increase, there is an essential need to address the ethical aspects of DCD in institutional DCD protocols and clinical practice. Ethical issues of respecting the end-of-life wishes of a potential donor, respecting a recipient’s wishes, and addressing potential conflicts of interest are important considerations in developing policies and procedures for DCD programs. Although there may be diversity among DCD programs in Europe, Australia, Israel, China, the United States, and Canada, addressing ethical considerations in these DCD programs is essential to respect donors and recipients during the altruistic and generous act of organ donation.
Identifying Barriers to Implementation of the National Partnership for Maternal Safety Obstetric Hemorrhage Bundle at a Tertiary Center: Utilization of the Delphi Method
Authors: De Tina Annemaria , Chau Anthony , Carusi Daniela A. , Robinson Julian N. , Tsen Lawrence C. , Farber Michaela K.
Published: May 2018

BACKGROUND:

In 2015, the National Partnership for Maternal Safety (NPMS) developed an obstetric hemorrhage consensus bundle to provide birthing facilities in the United States with consistent, validated practice guidelines for postpartum hemorrhage management. The process of implementing each bundle element at a large tertiary labor and delivery unit has not been described; we sought to identify practice deficiencies and perceived barriers to bundle implementation among multidisciplinary providers.

METHODS:

We conducted a prospective, cross-sectional, consensus-building study based on the Delphi method. A multidisciplinary expert panel comprised of anesthesiologists, obstetricians, nurses, and surgical technicians was assembled and participated in 4 sequential questionnaires. The first round identified bundle elements that experts determined as not currently adequate and perceived barriers to implementation. The second round established prioritization of elements within each professional group; and the third round ranked the elements with at least 60% agreement on feasibility of implementation and positive impact on patient care. The last round revealed responses across all 4 professional groups to derive a final consensus. Descriptive statistics were performed.

RESULTS:

A total of 38 experts completed the study (11 anesthesiologists, 11 obstetricians, 10 nurses, and 6 surgical technicians). While all 13 (100%) NPMS obstetric bundle elements were described as deficient in our labor and delivery unit by a provider in at least 1 discipline, consensus among at least 3 of the 4 disciplines was achieved for 6 element deficiencies. Barriers to implementation were determined. The initiatives that achieved consensus as possessing high patient impact and implementation feasibility were protocol-driven management, unit-based simulation drills, blood loss quantification, and team huddles and debriefings.

CONCLUSIONS:

The NPMS obstetric hemorrhage bundle was created to help guide practice and systems improvement for US birthing facilities. The Delphi method enabled identification of deficient elements and perceived barriers to element implementation, as well as group consensus on elements with highest patient impact and feasibility. Multidisciplinary group consensus can identify deficiencies and promote tangible, quality improvements in a large, tertiary-care labor and delivery unit. Institutions may utilize our described technique to guide implementation of future care bundles.
CLERK is a novel receptor kinase required for sensing of root-active CLE peptides in Arabidopsis
Authors: Anne Pauline , Amiguet-Vercher Amelia , Brandt Benjamin , Kalmbach Lothar , Geldner Niko , Hothorn Michael , Hardtke Christian S.
Published: May 2018

CLAVATA3/EMBRYO SURROUNDING REGION (CLE) peptides are secreted endogenous plant ligands that are sensed by receptor kinases (RKs) to convey environmental and developmental inputs. Typically, this involves an RK with narrow ligand specificity that signals together with a more promiscuous co-receptor. For most CLEs, biologically relevant (co-)receptors are unknown. The dimer of the receptor-like protein CLAVATA 2 (CLV2) and the pseudokinase CORYNE (CRN) conditions perception of so-called root-active CLE peptides, the exogenous application of which suppresses root growth by preventing protophloem formation in the meristem. clv2 as well as crn null mutants are resistant to root-active CLE peptides, possibly because CLV2-CRN promotes expression of their cognate receptors. Here, we have identified the CLE-RESISTANT RECEPTOR KINASE (CLERK) gene, which is required for full sensing of root-active CLE peptides in early developing protophloem. CLERK protein can be replaced by its close homologs, SENESCENCE-ASSOCIATED RECEPTOR-LIKE KINASE (SARK) and NSP-INTERACTING KINASE 1 (NIK1). Yet neither CLERK nor NIK1 ectodomains interact biochemically with described CLE receptor ectodomains. Consistently, CLERK also acts genetically independently of CLV2-CRN. We, thus, have discovered a novel hub for redundant CLE sensing in the root.
The Mauthner cell in a fish with top-performance and yet flexibly-tuned C-starts II. Physiology
Authors: Machnik Peter , Leupolz Kathrin , Feyl Sabine , Schulze Wolfram , Schuster Stefan
Published: May 2018

The parallel occurrence in archerfish of fine-tuned and yet powerful predictive C-starts as well as of kinematically identical escape C-starts makes archerfish an interesting system to test hypotheses on the roles played by the Mauthner cells, a pair of giant reticulospinal neurons. In this study we show that the archerfish Mauthner cell shares all hallmark physiological properties with that of goldfish. Visual and acoustic inputs are received by the ventral and lateral dendrite, respectively, and cause complex postsynaptic potentials (PSPs) even in surgically anaesthetised fish. PSP shape did not indicate major differences between the species, but simple light flashes caused larger PSPs in archerfish, often driving the cell to fire an action potential. Probing archerfish in the classical tests for feedback inhibition, established in the Mauthner-associated networks in goldfish, revealed no differences between the two species, including the indications for electrical and chemical synaptic components. Also the established hallmark experiments on feed-forward inhibition showed no differences between the goldfish and archerfish Mauthner system. Extending these experiments to visual stimuli also failed to detect any differences between the two species and suggests that acoustical and visual input cause feed-forward inhibition, whose magnitude, time course and duration matches that of the respective PSPs both in archerfish and goldfish. Our findings question simple views on the role of the Mauthner cell and suggest that the archerfish Mauthner cell should be a good system to explore the function of these giant neurons in more sophisticated C-start behaviours.
The Mauthner cell in a fish with top-performance and yet flexibly-tuned C-starts I. Identification and comparative morphology
Authors: Machnik Peter , Leupolz Kathrin , Feyl Sabine , Schulze Wolfram , Schuster Stefan
Published: May 2018

Archerfish use two powerful C-starts: One to escape threats, the other to secure prey that they have downed with a shot of water. The two C-starts are kinematically equivalent, are variable in both phases, and the predictive C-starts – used in hunting – are adjusted in the angle of turning and in the final linear speed to where and when their prey will hit the water surface. Presently nothing is known about the circuits that drive the archerfish C-starts. As the starting point for a neuroethological analysis, we first explored the presence and morphology of any paired Mauthner cell, a key cell in the teleost fast-start system. We show that archerfish have a typical Mauthner cell in each medullary hemisphere and that these send by far the largest axons down the spinal cord. Stimulation of the spinal cord caused short-latency all-or-none field potentials that could be detected even at the surface of the medulla and that had the archerfish Mauthner cell as its only source. The archerfish's Mauthner cell is remarkably similar morphologically to that of equally sized goldfish, except that the archerfish's ventral dendrite is slightly longer and its lateral dendrite thinner. Our data provide the necessary starting point for the dissection of the archerfish fast-start system and of any role potentially played by its Mauthner cell in the two C-start manoeuvres. Moreover, they do not support the recently expressed view that Mauthner cells should be reduced in animals with highly variable fast-start manoeuvres.
Isometric versus Dynamic Measurements of Fatigue: Does Age Matter? A Meta-analysis
Authors: KRÜGER RENATA L. , ABOODARDA SAIED JALAL , SAMOZINO PIERRE , RICE CHARLES L. , MILLET GUILLAUME Y.
Published: May 2018

Purpose

The assessment of power changes after fatiguing exercise provides important additional information about neuromuscular function compared with traditional isometric measurements, especially when exploring age-related changes in fatigability. Therefore, the aim of this review was to explore the effects of age on neuromuscular fatigue (NMF) when measured in isometric compared with dynamic contractions. The importance of central and peripheral mechanisms contributing to age-related NMF was discussed.

Methods

Medline, EMBASE, Cochrane Central Register of Controlled Trials, and SPORT Discus databases were searched. The combination of terms related to the intervention (fatiguing exercise), population (old people) and outcomes (isometric force and power) were used. This meta-analysis was registered on PROSPERO (CRD42016048389).

Results

Thirty-one studies were included. The meta-analyses revealed that force decrease was greater (there was more NMF) in young subjects than their older counterparts when fatigue was induced by isometric tasks (effect size [ES], 0.913; confidence interval [CI], 0.435–1.391; P < 0.001), but not when the fatiguing exercise was performed in dynamic mode (ES, 0.322; CI, −0.039 to 0.682; P = 0.08). Older individuals demonstrated a greater reduction in power after fatigue induced by either dynamic or isometric tasks (ES, −0.891; CI, −1.657 to −0.125; P = 0.023).

Conclusions

There is no difference in the isometric force loss between young and old people when fatigue is induced by dynamic tasks. However, maximal power is more decreased after fatigue tasks in older adults. Thus, the assessment of fatigue (isometric force vs power) must be considered in identifying age-related NMF mechanisms.
Hypothermia Decreases O2 Cost for Ex Vivo Contraction in Mouse Skeletal Muscle
Authors: FERRARA PATRICK J. , VERKERKE ANTHONY R. P. , BRAULT JEFFREY J. , FUNAI KATSUHIKO
Published: May 2018

Introduction

Evidence suggests that the energy efficiency of key ATPases involved in skeletal muscle contractile activity is improved in a hypothermic condition. However, it is unclear how a decrease in temperature affects skeletal muscle O2 consumption (mVO2) induced by muscle contraction.

Methods

Isolated mouse extensor digitorum longus (EDL) muscles were incubated in a temperature-controlled (37°C or 25°C) bath that included an O2 probe. EDL muscles from one limb were subjected to the measurement of resting mVO2, and the contralateral EDL muscles were used for the measurement of mVO2 with electrically stimulated contraction. For the resting protocol, muscles were suspended at resting tension for 15 min with continuous O2 recordings. For the contraction protocol, EDL muscles underwent 10 electrically stimulated isometric contractions with continuous O2 recordings for 15 min. The rate of O2 disappearance was quantified as micromoles of O2 per minute and normalized to the wet weight of the muscle.

Results

Resting mVO2 was greater at 37°C than at 25°C, consistent with the idea that lower temperature reduces basal metabolic rate. Electrically stimulated contraction robustly increased mVO2 at both 37°C and 25°C, which was sustained for ~3 min postcontraction. During that period, mVO2 was elevated approximately fivefold at both 37°C and 25°C. Greater contraction-induced mVO2 at 37°C compared with 25°C occurred despite lower force generated at 37°C than at 25°C.

Conclusions

Together, O2 cost for muscle contraction (force–time integral per O2 consumed) was greater at 37°C than at 25°C. Levels of high-energy phosphates were consistent with greater energy demand at 37°C compared with 25°C. In conclusion, these results indicate that muscle contraction that occurs at subnormal temperature requires less O2 than at 37°C.
Maternal Physical Activity and Sex Impact Markers of Hepatic Mitochondrial Health
Authors: CUNNINGHAM RORY P. , MOORE MARY P. , MEERS GRACE M. , RUEGSEGGER GREGORY N. , BOOTH FRANK W. , RECTOR R. SCOTT
Published: May 2018

Introduction

Maternal exercise and physical activity during the gestational period can be protective against maternal high-fat diet–induced hepatic steatosis in older offspring. However, it is unknown whether these protective effects are seen in younger offspring. In this study, we investigated whether maternal physical activity would attenuate maternal western diet (WD)–induced steatosis in young adult rats.

Methods

Female Wistar rats (7–8 wk of age) were randomized into WD (42% fat, 27% sucrose) or normal chow diet (ND), and further randomized into physical activity (RUN) or sedentary (SED) conditions for a total of four groups. Dams returned to ND/SED conditions after parturition. Postweaning, offspring were maintained in ND/SED conditions for 18 wk.

Results

Maternal WD-induced increases in male offspring body mass was attenuated in the WD/RUN offspring (P < 0.05). Maternal WD feeding significantly increased hepatic steatosis in male (but not female offspring), which was not attenuated by maternal RUN. However, maternal RUN increased (P < 0.05) hepatic markers of mitochondrial biogenesis and mitophagy (mitochondrial transcription factor A, peroxisome proliferator activator receptor γ, and nuclear factor E2–related factor 2) in all offspring and the mitophagy marker BCL2-interacting protein 3 in WD/RUN offspring. Interestingly, hepatic markers of de novo lipogenesis (fatty acid synthase and acetyl coenzyme A carboxylase), mitophagy (autophagy-related gene 12:5, BCL2-interacting protein 3, P62, and LC3 II/I), and mitochondria biogenesis/content (mitochondrial transcription factor A and OXPHOS-Complex II) were significantly increased in female versus male offspring.

Conclusion

Although maternal physical activity did not attenuate maternal WD-induced hepatic steatosis as has been previously reported in older adult offspring, it did significantly increase hepatic markers of mitochondrial biogenesis and mitophagy. Furthermore, female offspring had elevated hepatic markers of mitochondrial health, possibly explaining why female rats are protected against maternal WD-induced hepatic steatosis. Future studies are warranted to shed light on the time line of hepatic steatosis development under the influence of maternal physical activity.
Workplace Signaling and Financial Commitment: Evidence from a Field Experiment
Authors: Breza Emily , Kanz Martin , Klapper Leora
Published: May 2018

We provide evidence of strategic behavior in financial decisions that occur in the workplace and are observable to one's employer. We offer factory workers the opportunity to sign up for a commitment savings account that credibly signals the intention to remain employed with the firm. Workers are more likely to sign up when the account is endorsed by their employer and their decision is observed by the firm. An experiment with the firm's managers shows that the firm is more likely to invest in the human capital of workers with accounts, suggesting that financial commitment is rewarded by the employer.