bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of episodic rainfall on aqueous metal mobility from historical mine sites
Authors: Valencia-Avellan Magaly , Slack Rebecca , Stockdale Anthony , Mortimer Robert John George
Published: March 2018

Environmental contextEpisodic extreme rainfall events may affect metal dynamics in rivers flowing within historical metal mining areas. This study provides an analysis of the water chemistry and geochemical processes associated with mobilisation of metals during episodic rainfall events. Findings could be used to assess the environmental quality of streams draining spoil waste areas with similar geochemical conditions, and thereby be used to guide future management strategies.
AbstractThe increasing frequency and magnitude of episodic rainfall events may affect historical metal mining areas by remobilisation and deposition of metal-rich sediments and enhancing metal-rich run off, impacting river water quality. This study assesses the effects of episodic rainfall in a Carboniferous headwater catchment contaminated by historical Pb and Zn mining. Comprehensive hourly water chemistry measurements combined with modelling using PHREEQC, WHAM/Model VII and WHAM-FTOX were used in this assessment. For the episodic event, we measured flow increases from a baseline of 0.05 to 2.12 m3 s−1 at peak flow. Changes in metal concentration were most marked for ephemeral tributary, with Pb increasing from a baseline concentration of 55 μg L−1 to a peak of 576 μg L−1. Behaviour for Pb showed great affinity to form organic complexes or bind to colloidal Al and Fe oxides, whereas for Zn and the tributary flowing subsurface a more complex behaviour was observed. For example, the dissolution of secondary metal carbonate minerals (e.g. smithsonite (ZnCO3)) is likely constrained by higher concentrations of carbonate and bicarbonate derived from increased bedrock weathering under flow conditions induced by episodic rainfall. The abundance of secondary mineral sources and circumneutral pH present during episodic rainfall are important factors controlling the mobilisation of Pb and Zn. Furthermore, episodic rainfall events could enhance metal toxicity but there are aggravating and mitigating factors that depend on site-specific chemical changes. Overall, this study highlighted the complexity of metal mobility and toxicity during these events.
Minimal prophylactic concentration of dietary zinc compounds in a mouse model of swine dysentery
Authors: Zhang Peng , Carlson Michael P. , Schneider Norman R. , Duhamel Gerald E.
Published: March 2018

Dietary supplementation with 6000 mg of Zn2+/kg of feed has been shown to modify the clinicopathologic expression ofBrachyspira hyodysenteriaeinfection in a laboratory mouse model of swine dysentery. However, this concentration impaired the body weight gain of the mice. The purpose of the present study was to determine a minimal prophylactic concentration of feed-grade zinc compounds that would not affect the growth of mice challenge-exposed withB. hyodysenteriae. A total of 440, 6- to 8-week-old, C3H/HeN mice were allocated randomly to groups and fed either a defined diet or a defined diet containing either 1000, 2000 or 4000 mg/kg ZnO, ZnSO4or zinc-methionine for 7 days before intra- gastric inoculation withB. hyodysenteriae. From days 7 to 35 after inoculation, mice in each group were necropsied at weekly intervals for determination of body weight, presence ofB. hyodysenteriaein the cecum, and histological assessment of cecal lesions. Only ZnO fed at 2000 mg/kg had a prophylactic effect againstB. hyodysenteriaeinfection without affecting the body weight gain of the mice. The prophylactic effect of Zn2+against infection withB. hyodysenteriaewas also affected by the relative concentration of Fe2+and Zn2+/Fe2+ratio of the diet.
Multidisciplinary group information for patients with tinnitus
Authors: Zarenoe Reza , Bohn Eriksson Therese , Dahl Jakob , Ledin Torbjörn , Andersson Gerhard
Published: March 2018

Purpose:

The aim of this study was to investigate the effects of a multidisciplinary group information as a part of a Stepped Care tinnitus management model. The Tinnitus Handicap Inventory (THI) and the Hospital Anxiety and Depression Scale (HADS) were administered before and after the group information to evaluate the effects.

Method:

In total, 627 patients participated in half-day tinnitus information meetings from 2004 to 2011 in our clinic. We retrieved 426 patients for analysis with complete scores on the THI, HADS, and a questionnaire covering background information. These three questionnaires were used before the information meeting, and the THI and HADS at a 1-month follow-up.

Results:

Significant decreases were found in scores on the THI (p < .001) and the HADS-A (p < .05), pre- and post-information session. However, no significant changes were observed on the HADS-D.

Conclusion:

An information meeting as a part of multidisciplinary Stepped Care model can be an effective initial approach to manage tinnitus, and serve as a filter for patients who need additional treatment.
Breast Shape Analysis With Curvature Estimates and Principal Component Analysis for Cosmetic and Reconstructive Breast Surgery
Authors: Catanuto Giuseppe , Taher Wafa , Rocco Nicola , Catalano Francesca , Allegra Dario , Milotta Filippo Luigi Maria , Stanco Filippo , Gallo Giovanni , Nava Maurizio Bruno
Published: March 2018

Background

Breast shape is defined utilizing mainly qualitative assessment (full, flat, ptotic) or estimates, such as volume or distances between reference points, that cannot describe it reliably.

Objectives

The authors quantitatively described breast shape with two parameters derived from a statistical methodology denominated by principal component analysis (PCA).

Methods

The authors created a heterogeneous dataset of breast shapes acquired with a commercial infrared 3-dimensional scanner on which PCA was performed. The authors plotted on a Cartesian plane the two highest values of PCA for each breast (principal components 1 and 2). Testing of the methodology on a preoperative and posttreatment surgical case and test-retest was performed by two operators.

Results

The first two principal components derived from PCA characterize the shape of the breast included in the dataset. The test-retest demonstrated that different operators obtain very similar values of PCA. The system is also able to identify major changes in the preoperative and posttreatment stages of a two-stage reconstruction. Even minor changes were correctly detected by the system.

Conclusions

This methodology can reliably describe the shape of a breast. An expert operator and a newly trained operator can reach similar results in a test/re-testing validation. Once developed and after further validation, this methodology could be employed as a good tool for outcome evaluation, auditing, and benchmarking.

Level of Evidence: 4
Evidence to Improve Physical Activity among Medically Underserved Older adults: A Scoping Review
Authors: Hu Yi-Ling , Junge Kristin , Nguyen An , Hiegel Kelsey , Somerville Emily , Keglovits Marian , Stark Susan
Published: March 2018

Background and Objectives

Participation in leisure physical activity (PA) and engagement in PA interventions among older adults is influenced by socioeconomic status (SES), race/ethnicity, and environment. However, studies of PA for medically underserved older adults have not yet been systematically evaluated. The objective of this study is to map the nature and extent of research conducted on PA participation, interventions, and components of effective leisure PA programs for medically underserved older adults.

Research Design and Methods

The five-stage approach was used to conduct this scoping review. We searched PubMed, CINAHL, and Cochrane Library for peer-reviewed studies published between 2006 and 2016. Data extracted from selected studies included study population, study type, purpose of intent, evidence level, barriers to PA participation, and components of PA intervention.

Results

Three hundred and ninety-two articles were identified, and 60 studies were included in the final data charting. Existing literature showed that most studies remained descriptive in nature, and few intervention studies have achieved a high level of evidence. Among 21 intervention studies, only 4 were explicitly conducted for older adults. Culturally adapted materials, race/ethnicity-specific barriers and facilitators, and form of intervention were important components for intervention programs.

Discussion and Implications

Findings indicate that more studies are needed to reduce health disparities related to PA participation for medically underserved older adults. Intervention components such as race/ethnicity-relevant barriers and facilitators and culturally sensitive materials are also needed for PA interventions targeting underserved older adults in order to provide evidence for best practices.
Comparative effects of temperature on rates of development and survival of eggs and yolk-sac larvae of Arctic cod (Boreogadus saida) and walleye pollock (Gadus chalcogrammus)
Authors: Laurel Benjamin J , Copeman Louise A , Spencer Mara , Iseri Paul
Published: March 2018

Changes in Arctic fish assemblages resulting from climate change will likely be determined by the differential thermal response of key species during their early life history. In this study, we incubated multiple batches of eggs and larvae of two ecologically important gadids co-occurring at the Pacific–Arctic interface, Arctic cod (Boreogadus saida) and walleye pollock (Gadus chalcogrammus). Fertilized egg batches (n = 11 Arctic cod; n = 6 walleye pollock) were collected in the late winter/early spring from laboratory broodstock held under simulated seasonal environmental conditions. Image and lipid analyses indicated that Arctic cod eggs and larvae were ∼25–35% larger than walleye pollock and had nearly 3–6× more energetic reserves. Two batches of eggs from each species were incubated in replicated containers (n = 3/batch/temperature) at −0.4, 1.2, 2.5, 3.8, 5.0, 9.0, and 12.0°C for Arctic cod and −0.8, 0.3, 2.2, 4.5, 9.0, and 12.0°C for walleye pollock. Both species had very similar low thermal tolerance, but Arctic cod were much more sensitive to higher thermal stress in terms of hatch success and size-at-hatch. For example, Arctic cod hatch success declined precipitously at temperatures above 3.5°C yet remained above 50% in walleye pollock at 9°C. Arctic cod also had significantly longer development times, such that embryos could survive for ∼4 months at temperatures <0°C from the time of spawning to first-feeding. Collectively, these results indicate Arctic cod have a much smaller thermal window for survival, but can survive for longer periods in the absence of food than walleye pollock at cold temperatures. These temperature-dependent rates will be useful in the development of population forecasts and biophysical transport models for these species in the northern Bering, Chukchi, and Beaufort seas.
Lztfl1/BBS17 controls energy homeostasis by regulating the leptin signaling in the hypothalamic neurons
Authors: Wei Qun , Gu Yi-Feng , Zhang Qing-Jun , Yu Helena , Peng Yan , Williams Kevin W , Wang Ruitao , Yu Kajiang , Liu Tiemin , Liu Zhi-Ping
Published: March 2018

Leptin receptor (LepRb) signaling pathway in the hypothalamus of the forebrain controls food intake and energy expenditure in response to an altered energy state. Defects in the LepRb signaling pathway can result in leptin-resistance and obesity. Leucine zipper transcription factor like 1 (Lztfl1)/BBS17 is a member of the Bardet–Biedl syndrome (BBS) gene family. Human BBS patients have a wide range of pathologies including obesity. The cellular and molecular mechanisms underlying Lztfl1-regulated obesity are unknown. Here, we generated Lztfl1f/f mouse model in which Lztfl1 can be deleted globally and in tissue-specific manner. Global Lztfl1 deficiency resulted in pleiotropic phenotypes including obesity. Lztfl1−/− mice are hyperphagic and showed similar energy expenditure as WT littermates. The obese phenotype of Lztfl1−/− mice is caused by the loss of Lztfl1 in the brain but not in the adipocytes. Lztfl1−/− mice are leptin-resistant. Inactivation of Lztfl1 abolished phosphorylation of Stat3 in the LepRb signaling pathway in the hypothalamus upon leptin stimulation. Deletion of Lztfl1 had no effect on LepRb membrane localization. Furthermore, we observed that Lztfl1−/− mouse embryonic fibroblasts (MEFs) have significantly longer cilia than WT MEFs. We identified several proteins that potentially interact with Lztfl1. As these proteins are known to be involved in regulation of actin/cytoskeleton dynamics, we suggest that Lztfl1 may regulate leptin signaling and ciliary structure via these proteins. Our study identified Lztfl1 as a novel player in the LepRb signaling pathway in the hypothalamus that controls energy homeostasis.
Clinical Features and Outcomes of Children with Culture-Negative Septic Arthritis
Authors: Spyridakis Evangelos , Gerber Jeffrey S , Schriver Emily , Grundmeier Robert W , Porsch Eric A , St. Geme Joseph W , Downes Kevin J
Published: March 2018

Background

Septic arthritis is a serious infection, but the results of blood and joint fluid cultures are often negative in children. We describe here the clinical features and management of culture-negative septic arthritis in children at our hospital and their outcomes.

Methods

We performed a retrospective review of a cohort of children with septic arthritis who were hospitalized at Children’s Hospital of Philadelphia between January 2002 and December 2014. Culture-negative septic arthritis was defined as a joint white blood cell count of >50000/μL with associated symptoms, a clinical diagnosis of septic arthritis, and a negative culture result. Children with pretreatment, an intensive case unit admission, Lyme arthritis, immunodeficiency, or surgical hardware were excluded. Treatment failure included a change in antibiotics, surgery, and/or reevaluation because of a lack of improvement/worsening.

Results

We identified 157 children with septic arthritis. The patients with concurrent osteomyelitis (n = 28) had higher inflammatory marker levels at presentation, had a longer duration of symptoms (median, 4.5 vs 3 days, respectively; P < .001), and more often had bacteremia (46.4% vs 6.2%, respectively; P < .001). Among children with septic arthritis without associated osteomyelitis, 69% (89 of 129) had negative culture results. These children had lower C-reactive protein levels (median, 4.0 vs 7.3 mg/dL, respectively; P = .001) and erythrocyte sedimentation rates (median, 39 vs 51 mm/hour, respectively; P = .01) at admission and less often had foot/ankle involvement (P = .02). Among the children with culture-negative septic arthritis, the inpatient treatment failure rate was 9.1%, and treatment failure was more common in boys than in girls (17.1% vs 3.8%, respectively; P = .03). We found no association between treatment failure and empiric antibiotics or patient age. No outpatient treatment failures occurred during the 6-month follow-up period, although 17% of the children discharged with a peripherally inserted central catheter line experienced complications, including 3 with bacteremia.

Conclusions

The majority of septic arthritis infections at our institution were culture negative. Among patients with culture-negative infection, empiric antibiotics failed for 9% and necessitated a change in therapy. More sensitive diagnostic testing should be implemented to elucidate the causes of culture-negative septic arthritis in children.
Which Interpretational Route Will the Supreme Court of India Follow When Faced with the Contentious Civil Liability for Nuclear Damage Act, 2010?
Authors: M P Ram Mohan
Published: March 2018

The Civil Nuclear Liability for Damages Act of India enacted in 2010 has been a matter of concern to international suppliers and vendors. This is due to the perceived deviation of the law from the principle of legal channelling of liability (to the operator) which is at the heart of international nuclear liability jurisprudence. Specifically, this notion arises from allowing recourse to suppliers under outside of the circumstances mentioned in the Annex of the Convention for Complementary Compensation. Sections 17 and 46 which embody this notion are subject to different interpretations, some of them implying the compliance of the Indian regime with the international nuclear liability regime and many others equally suggest otherwise. In 2015, Government of India through a detailed Frequently Answered Questions clarified the nature and meaning of these sections. However, interestingly, there are two cases pending before Supreme Court of India contesting the constitutionality of the legislation in which these two specific provisions are also disputed. The article attempts to explain and resolve the ambiguity through a study of Supreme Court’s approach to statutory interpretation. I undertake an analysis of the reasoning given under the 2015 FAQ in the light of the disputed Sections 17 and 46 and bring out a probable prediction of Court’s interpretation of the Sections of the Act.
Patient and System Characteristics Associated with Performance on the HEDIS Measures of Alcohol and Other Drug Treatment Initiation and Engagement
Authors: Yarborough Bobbi Jo H. , Chi Felicia W. , Green Carla A. , Hinman Agatha , Mertens Jennifer , Beck Arne , Horberg Michael , Weisner Constance , Campbell Cynthia I.
Published: March 2018

Objectives:

Understand patient and system characteristics associated with performance on the Healthcare Effectiveness Data and Information Set (HEDIS) Alcohol and Other Drug (AOD) Initiation and Engagement of Treatment (IET) measures.

Methods:

This mixed-methods study linked patient and health system data from four Kaiser Permanente regions to HEDIS performance measure data for 44,320 commercially or Medicare-insured adults with HEDIS-eligible AOD diagnoses in 2012. Characteristics associated with IET were examined using multilevel logistic regression models. Key informant interviews (n = 18) focused on opportunities to improve initiation and engagement.

Results:

Non-white race/ethnicity, alcohol abuse, or nonopioid drug abuse diagnoses were associated with lower odds of treatment initiation among commercially insured. For both insurance groups, those diagnosed in healthcare departments other than specialty AOD treatment were less likely to initiate or engage in treatment. Being diagnosed in facilities with co-located AOD/primary care clinics, and those with medications for addiction treatment available, was each associated with higher odds of initiation and engagement for both commercially and Medicare-insured. Having behavioral medicine specialists or clinical health educators in primary care increased initiation and engagement odds among commercially insured. Key informants recommended were as follows: patient-centered care; increased treatment choices; cross-departmental patient identification, engagement, and coordination; provider education; and use of informatics/technology.

Conclusions:

Tailoring treatment, enhancing treatment motivation among individuals with lower severity diagnoses, offering medication treatment of addiction, clinician education, care coordination, co-located AOD and primary care departments, and behavioral medicine specialists in primary care may improve rates of initiation and engagement in AOD treatment.
Preoperative Chronic Opioid Therapy
Authors: Jain Nikhil , Phillips Frank M. , Weaver Tristan , Khan Safdar N.
Published: March 2018

Study Design.

Retrospective, economic analysis.

Objective.

To study patient profile associated with preoperative chronic opioid therapy (COT), and study COT as a risk factor for 90-day complications, emergency department (ED) visits, and readmission after primary one- to two-level posterior lumbar fusion (PLF) for degenerative spine disease. We also evaluated associated costs, risk factors, and adverse events related to long-term postoperative opioid use.

Summary of Background Data.

Chronic opioid use is associated with poor outcomes and dependence after spine surgery. Risk factors, complications, readmissions, adverse events, and costs associated with COT in patients undergoing lumbar fusion are not entirely known. As providers look to reduce healthcare costs and improve outcomes, identification of modifiable risk factors is important.

Methods.

Commercial insurance data from 2007 to Q3–2015 was used to study preoperative opioid use in patients undergoing primary one- to two-level PLF. Ninety-day complications, ED visits, readmissions, 1-year adverse events, and associated costs have been described. Multiple-variable regression analyses were done to study preoperative COT patient profile and opioid use as a risk factor for complications and adverse events.

Results.

A total of 24,610 patients with a mean age of 65.6 ± 11.5 years were included. Five thousand five hundred (22.3%) patients had documented opioid use for more than 6 months before surgery, and 87.4% of these had continued long-term use postoperatively. On adjusted analysis, preoperative COT was found to be a risk factor for 90-day wound complications, pain diagnoses, ED visits, readmission, and continued use postoperatively. Postspinal fusion long-term opioid users had an increased utilization of epidural/facet joint injections, risk for revision fusion, and increased incidence of new onset constipation within 1 year postsurgery. The cost associated with increase resource use in these patients has been reported.

Conclusion.

Preoperative COT is a modifiable risk factor for complications, readmission, adverse events, and increased costs after one- or two-level PLF.

Level of Evidence: 3
Negative correlation of high-density lipoprotein-cholesterol and bone mineral density in postmenopausal Iranian women with vitamin D deficiency
Authors: Maghbooli Zhila , Khorrami-nezhad Leila , Adabi Elham , Ramezani Majid , Asadollahpour Effat , Razi Farideh , Rezanejad Mohamadtaher
Published: March 2018

Objective:

The aim of the study was to investigate the association between high-density lipoprotein (HDL) and bone status taking into account serum vitamin D levels in postmenopausal Iranian women.

Methods:

During January 2015 and February 2016, a total of 488 postmenopausal Iranian women participated in this cross-sectional study, all of whom were not taking osteoporosis medication and were not suffering from any chronic disorder. Dual X-ray absorptiometry was used to assess bone mineral density (BMD) of the total hip, femoral neck, and lumbar vertebrae (L2-L4). Each person was categorized based on the World Health Organization osteoporosis criteria in at least one skeletal region. At the end of the data collection, lipid profiles and vitamin D levels were measured for all participants. Vitamin D serum levels less than 30 ng/mL were defined as vitamin D deficiency or insufficiency.

Results:

27.9% of all participants displayed osteoporosis. Osteoporotic participants tended to be older with higher HDL serum levels (P < 0.001). No significant difference was seen in low-density of lipoprotein, total triglyceride, and total cholesterol levels among participants (P > 0.05). In a univariate model, after adjusting for age, menopausal age, obesity, physical activity, and use of antihyperlipidemic drugs (statins), there were significant negative associations among HDL levels and BMD values and T-score in the three regions (P < 0.004). Interestingly, after classification of participants based on vitamin D levels and adjustment for confounding factors, these significant negative associations between HDL levels and BMD values as well as T-score were observed only in participants with vitamin D deficiency or insufficiency, in the three regions (P < 0.008).

Conclusions:

Our data show that in postmenopausal women with vitamin D deficiency, serum levels of HDL have negative correlation with bone status.
The Influence of Corneal Biomechanical Properties on Intraocular Pressure Measurements Using a Rebound Self-tonometer
Authors: Brown Lyndsay , Foulsham William , Pronin Savva , Tatham Andrew J.
Published: March 2018

Purpose:

The purpose of this study was to examine the effect of corneal biomechanical properties on intraocular pressure (IOP) measurements obtained using a rebound self-tonometer (Icare HOME) compared with Goldmann applanation tonometry (GAT).

Methods:

An observational study of 100 patients with glaucoma or ocular hypertension. All had a comprehensive ophthalmic examination and standard automated perimetry. IOP was assessed by GAT, Icare HOME and Ocular Response Analyzer, which was also used to assess corneal hysteresis (CH) and corneal resistance factor (CRF). Central corneal thickness (CCT) was recorded.

Results:

Mean (±SD) IOP measurements were 14.3±3.9 and 11.7±4.7 mm Hg using GAT and Icare HOME, respectively. Average CCT, CRF, and CH were 534.5±37.3 μm, 9.0±1.7 mm Hg, and 9.4±1.5 mm Hg, respectively. The mean difference between Icare HOME and GAT was −2.66±3.13 mm Hg, with 95% limits of agreement of −8.80 to 3.48 mm Hg, however, there was evidence of proportional bias. There was negative correlation between IOP and CH [5.17 mm Hg higher Icare HOME IOP (P=0.041, R
2=0.029) and 7.23 mm Hg higher GAT IOP (P=0.008, R
2=0.080) for each 10 mm Hg lower CH], whereas thinner CCT was significantly associated with lower IOP (P<0.001, R
2=0.14 for Icare HOME and P<0.001, R
2=0.08 for GAT). In multivariable analysis, although CRF and CH remained associated with IOP measured using either GAT or Icare HOME, CCT was no longer significant.

Conclusion:

IOP measurements obtained using a self-tonometer, similar to GAT, were more influenced by overall corneal biomechanics than CCT.
Factors Associated With Early Virological Response in HIV-Infected Individuals Starting Antiretroviral Therapy in Brazil (2014–2015): Results From a Large HIV Surveillance Cohort
Authors: Meireles Mariana V. , Pascom Ana Roberta P. , Duarte Elisabeth C.
Published: March 2018

Objective:

To identify clinical, sociodemographic, and treatment-related factors associated with early virological response in HIV-infected adults starting antiretroviral treatment (ART) in Brazil in 2014–2015.

Methods:

Data from 4 information systems from the Brazilian AIDS Program were combined to create a historical cohort. Unconditional logistic regression models were used to assess the likelihood of not achieving viral load suppression (VLS), defined as having either a viral load (VL) count >200 copies per milliliter or an aids-related death recorded within 180 ± 90 days after treatment initiation.

Results:

Among 76,950 individuals, 64.8% were men; median age, CD4+, and VL counts were 34 years, 378 cells per micro liter, and 38,131 copies per milliliter, respectively, and 85.2% achieved VLS. In the multivariate analysis, some factors which increased the odds of non-VLS were as follows: lower CD4+ and higher VL counts, younger age, heterosexual or injection drug use groups (relative to men who have sex with men), lower educational level, black/brown race, higher pill burden, and higher dosing frequency. Regimens containing boosted protease inhibitors were similar to those containing nonnucleoside reverse transcriptase inhibitors and superior to those containing unboosted protease inhibitors (all P values <0.001). No difference was observed between patients with CD4+ counts 350–499 and 500+ cells per micro liter.

Conclusions:

Our findings support the decision made in Brazil in 2013 to recommend immediate initiation of ART regardless of clinical stage or CD4+. Several factors were found to be associated with poorer virologic outcomes and should be addressed to maximize ART adherence and success rates.
Four-Minute Bone SPECT Using Large-Field Cadmium-Zinc-Telluride Camera
Authors: Gregoire Bastien , Pina-Jomir Géraldine , Bani-Sadr Alexandre , Moreau-Triby Caroline , Janier Marc , Scheiber Christian
Published: March 2018

Purpose

The aim of this study was to determine the minimum acquisition time without decreasing lesion detectability of bone SPECT using a whole-body cadmium-zinc-telluride camera.

Methods

Patients referred for bone SPECT were retrospectively included. SPECT of 30 patients were reframed from native data (16 s/projection) to produce 10-, 5-, and 3-s/projection data sets. A “critical” acquisition time/projection was defined as that below which the SPECT quality becomes insufficient for interpretation, as determined by 3 reviewers using a 4-point scale (0 = quality insufficient for interpretation, 1 = average, 2 = good, 3 = excellent). Three reviewers (blinded to the acquisition time) evaluated SPECT data sets (n = 79), native and reframed with “critical” acquisition times, in a randomized order. A lesion was defined as any uptake considered pathological by a reviewer. Lesion detectability equivalence between native SPECT and reframed SPECT was assessed by calculating a coefficient (κ) for each reviewer.

Results

Image quality of the first sample (n = 30) was significantly and progressively less well graded for the reframed data sets by all reviewers. Only 1 patient was graded 0 by each reviewer for the 5-s/projection data set. For the 3-s/projection data set, 3 patients were graded 0. No patients were graded 0 for 10-s/projection data set. The minimal acquisition time, for each projection, was defined as 5 s/projection. The coefficient κ, between native and reframed, with critical acquisition time/projection SPECT was greater than 0.9 for each reviewer.

Conclusions

The more contrasted images of the cadmium-zinc-telluride camera allow performance of 5-s/projection SPECT without loss of lesion detectability. This suggests the possibility of performing whole-body SPECT in a reasonable time or reducing injected doses, especially in pediatric patients.
Patient-Selected Strategies for Post Cardiac Rehabilitation Exercise Adherence in Heart Failure
Authors: Nielsen Jessica , Duncan Kathleen , Pozehl Bunny
Published: March 2018

Purpose

The aim of this study was to evaluate the use of patient-selected exercise adherence strategies following cardiac rehabilitation (CR).

Design

Twenty patients with heart failure (HF) were recruited and randomly assigned to the intervention or control group at completion of CR.

Methods

The intervention included the use of six adherence strategies (logs, graphs, pedometers, phone follow-up, education, and a letter from CR staff), which were provided for 6 weeks post CR and during home-based exercise. After 6 weeks, the intervention group selected strategies to continue, and only those were provided for the last 6 weeks. At 12 weeks, patients were retested.

Findings

Patients with HF demonstrated improvement in distance walked and less HF symptoms and adhered to exercise at levels recommended during CR.

Conclusion

Inclusion of patient-selected adherence strategies supports continued exercise and helps to sustain physiological improvements.

Clinical Relevance

Results from this study have implications for CR programs serving HF patients and provide insight into adherence strategies.
The S100A10 Pathway Mediates an Occult Hyperfibrinolytic Subtype in Trauma Patients
Authors: Gall Lewis S. , Vulliamy Paul , Gillespie Scarlett , Jones Timothy F. , Pierre Rochelle S. J. , Breukers Sabine E. , Gaarder Christine , Juffermans Nicole P. , Maegele Marc , Stensballe Jakob , Johansson Pär I. , Davenport Ross A. , Brohi Karim
Published: March 2018

Objective:

To determine the characteristics of trauma patients with low levels of fibrinolysis as detected by viscoelastic hemostatic assay (VHA) and explore the underlying mechanisms of this subtype.

Background:

Hyperfibrinolysis is a central component of acute traumatic coagulopathy but a group of patients present with low levels of VHA-detected fibrinolysis. There is concern that these patients may be at risk of thrombosis if empirically administered an antifibrinolytic agent.

Methods:

A prospective multicenter observational cohort study was conducted at 5 European major trauma centers. Blood was drawn on arrival, within 2 hours of injury, for VHA (rotation thromboelastometry [ROTEM]) and fibrinolysis plasma protein analysis including the fibrinolytic mediator S100A10. An outcomes-based threshold for ROTEM hypofibrinolysis was determined and patients grouped by this and by D-dimer (DD) levels.

Results:

Nine hundred fourteen patients were included in the study. The VHA maximum lysis (ML) lower threshold was determined to be <5%. Heterogeneity existed among patients with low ML, with survivors sharing similar clinical and injury characteristics to patients with normal ML values (5–15%). Those who died were critically injured with a preponderance of traumatic brain injury and had a 7-fold higher DD level (died vs. survived: 103,170 vs. 13,672 ng/mL, P < 0.001). Patients with low ML and high DD demonstrated a hyperfibrinolytic biomarker profile, low tissue plasminogen activator levels but high plasma levels of S100A10. S100A10 was negatively correlated with %ML (r = −0.26, P < 0.001) and caused a significant reduction in %ML when added to whole blood ex-vivo.

Conclusions:

Patients presenting with low ML and low DD levels have low injury severity and normal outcomes. Conversely, patients with low ML but high DD levels are severely injured, functionally coagulopathic and have poor clinical outcomes. These patients have low tissue plasminogen activator levels and are not detectable by ROTEM. S100A10 is a cell surface plasminogen receptor which may drive the hyperfibrinolysis in these patients and which when shed artificially lowers %ML ex-vivo.
Association Between Hospital Participation in Medicare Shared Savings Program Accountable Care Organizations and Readmission Following Major Surgery
Authors: Borza Tudor , Oerline Mary K. , Skolarus Ted A. , Norton Edward C. , Dimick Justin B. , Jacobs Bruce L. , Herrel Lindsey A. , Ellimoottil Chad , Hollingsworth John M. , Ryan Andrew M. , Miller David C. , Shahinian Vahakn B. , Hollenbeck Brent K.
Published: March 2018

Objective:

To evaluate the effect of Medicare Shared Savings Program accountable care organizations (ACOs) on hospital readmission after common surgical procedures.

Summary Background Data:

Hospital readmissions following surgery lead to worse patient outcomes and wasteful spending. ACOs, and their associated hospitals, have strong incentives to reduce readmissions from 2 distinct Centers for Medicare and Medicaid Services policies.

Methods:

We performed a retrospective cohort study using a 20% national Medicare sample to identify beneficiaries undergoing 1 of 7 common surgical procedures—abdominal aortic aneurysm repair, colectomy, cystectomy, prostatectomy, lung resection, total knee arthroplasty, and total hip arthroplasty—between 2010 and 2014. The primary outcome was 30-day risk-adjusted readmission rate. We performed difference-in-differences analyses using multilevel logistic regression models to quantify the effect of hospital ACO affiliation on readmissions following these procedures.

Results:

Patients underwent a procedure at one of 2974 hospitals, of which 389 were ACO affiliated. The 30-day risk-adjusted readmission rate decreased from 8.4% (95% CI, 8.1–8.7%) to 7.0% (95% CI, 6.7–7.3%) for ACO affiliated hospitals (P < 0.001) and from 7.9% (95% CI, 7.8–8.0%) to 7.1% (95% CI, 6.9–7.2%) for non-ACO hospitals (P < 0.001). The difference-in-differences of the 2 trends demonstrated an additional 0.52% (95% CI, 0.97–0.078%) absolute reduction in readmissions at ACO hospitals (P = 0.021), which would translate to 4410 hospitalizations avoided.

Conclusion:

Readmissions following common procedures decreased significantly from 2010 to 2014. Hospital affiliation with Shared Savings ACOs was associated with significant additional reductions in readmissions. This emphasis on readmission reduction is 1 mechanism through which ACOs improve value in a surgical population.
Viruses have multiple paths to central nervous system pathology
Authors: Agner Shannon C. , Klein Robyn S.
Published: March 2018

Purpose of review

Although viral infections of the central nervous system (CNS) are known to acutely cause pathology in the form of cytokine-mediated neural tissue damage and inflammation, the pathophysiology of neurologic sequelae after viral clearance is incompletely understood.

Recent findings

Alterations in microglial and glial biology in response to initial infiltration of immune cells that persist within the CNS have recently been shown to promote neuronal dysfunction and cognitive deficits in animal models of viral encephalitis.

The current review summarizes the current knowledge on the possible role of innate immune signaling during acute infections as triggers of neurologic sequelae that persist, and may even worsen, after clearance of viral infections within the CNS.
Altered Bile Acid Profile Associates with Cognitive Impairment in Alzheimer’s Disease – An Emerging Role for Gut Microbiome
Authors: MahmoudianDehkordi Siamak , Arnold Matthias , Nho Kwangsik , Ahmad Shahzad , Jia Wei , Xie Guoxiang , Louie Gregory , Kueider-Paisley Alexandra , Moseley M. Arthur , Thompson J. Will , John Williams Lisa St , Tenenbaum Jessica D. , Blach Colette , Baillie Rebecca , Han Xianlin , Bhattacharyya Sudeepa , Toledo Jon B. , Schafferer Simon , Klein Sebastian , Koal Therese , Risacher Shannon L. , Kling Mitchel Allan , Motsinger-Reif Alison , Rotroff Daniel M. , Jack John , Hankemeier Thomas , Bennett David A. , De Jager Philip L. , Trojanowski John Q. , Shaw Leslie M. , Weiner Michael W. , Doraiswamy P. Murali , van Duijn Cornelia M. , Saykin Andrew J. , Kastenmüller Gabi , Kaddurah-Daouk Rima ,   for the Alzheimer’s Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium
Published: March 2018

Introduction

Increasing evidence suggests a role for the gut microbiome in central nervous system disorders and specific role for the gut-brain axis in neurodegeneration. Bile acids (BA), products of cholesterol metabolism and clearance, are produced in the liver and are further metabolized by gut bacteria. They have major regulatory and signaling functions and seem dysregulated in Alzheimer disease (AD).

Methods

Serum levels of 15 primary and secondary BAs and their conjugated forms were measured in 1,464 subjects including 370 cognitively normal older adults (CN), 284 with early mild cognitive impairment (MCI), 505 with late MCI, and 305 AD cases enrolled in the AD Neuroimaging Initiative. We assessed associations of BA profiles including selected ratios with diagnosis, cognition, and AD-related genetic variants, adjusting for cofounders and multiple testing.

Results

In AD compared to CN, we observed significantly lower serum concentrations of a primary BA (cholic acid CA) and increased levels of the bacterially produced, secondary BA, deoxycholic acid (DCA), and its glycine and taurine conjugated forms. An increased ratio of DCA:CA, which reflects 7α-dehydroxylation of CA by gut bacteria, strongly associated with cognitive decline, a finding replicated in serum and brain samples in the Rush Religious Orders and Memory and Aging Project. Several genetic variants in immune response related genes implicated in AD showed associations with BA profiles.

Conclusion

We report for the first time an association between altered BA profile, genetic variants implicated in AD and cognitive changes in disease using a large multicenter study. These findings warrant further investigation of gut dysbiosis and possible role of gut liver brain axis in the pathogenesis of AD.
Motor Responses Influence Perceptual Awareness Judgements
Authors: Siedlecka Marta , Hobot Justyna , Skóra Zuzanna , Paulewicz Borysław , Timmermans Bert , Wierzchoń Michał
Published: March 2018

Perception and action are tightly related, but what is the relation between perceptual awareness and action? In this study we tested the hypothesis that motor response influences perceptual awareness judgements. We design a procedure in which participants were asked to decide whether Gabor grating was oriented towards the left or the right. Presentation of the stimuli was immediately followed by a cue requiring motor response that was irrelevant to the task but could be the same, opposite or neutral to the correct response to the Gabor patch. After responding to the cue participants were asked to rate their stimulus awareness using Perceptual Awareness Scale and then to report their discrimination decision.

The results showed that participants reported a higher level of stimulus awareness after carrying out responses that were either congruent or incongruent with a response required by a stimulus, compared to the neutral condition. The results suggest that directional motor response (congruent or incongruent with correct response to the stimulus) provides information about the decision process and its outcome increasing reported awareness of a stimulus.
The first next-generation sequencing approach to the mitochondrial phylogeny of African monogenean parasites (Platyhelminthes: Gyrodactylidae and Dactylogyridae)
Authors: Vanhove Maarten P.M. , Briscoe Andrew G. , Jorissen Michiel W.P. , Littlewood D. Tim J. , Huyse Tine
Published: March 2018

Background

Monogenean flatworms are the main ectoparasites of fishes. Representatives of the species-rich families Gyrodactylidae and Dactylogyridae, especially those infecting cichlid fishes and clariid catfishes, are important parasites in African aquaculture, even more so due to the massive anthropogenic translocation of their hosts worldwide. Several questions on their evolution, such as the phylogenetic position ofMacrogyrodactylusand the highly specioseGyrodactylus, remain unresolved with available molecular markers. Also, diagnostics and population-level research would benefit from the development of higher-resolution genetic markers. We aim to advance genetic work on African monogeneans by providing mitogenomic data of four species (two each belonging to the Gyrodactylidae and Dactylogyridae), and analysing their gene sequences and gene order from a phylogenetic perspective.

Results

Based on Illumina technology, the first four mitochondrial genomes of African monogeneans were assembled and annotated for the cichlid parasitesGyrodactylus nyanzae,Cichlidogyrus halli,Cichlidogyrus mbirizei(near-complete mitogenome) and the catfish parasiteMacrogyrodactylus karibae(near-complete mitogenome). The start codon TTG is new forGyrodactylusand for the Dactylogyridae, as is the incomplete stop codon TA for the Dactylogyridae. The most variable markers arenadgenes and these are under relaxed selection. Especiallynad2 is promising for primer development. Gene order was identical for protein-coding genes and differed between the African representatives of these families only in a tRNA gene transposition. A mitochondrial phylogeny based on an alignment of nearly 12,500 bp including 12 protein-coding and two ribosomal RNA genes confirms that the Neotropical oviparousAglaiogyrodactylus forficulatustakes a sister group position with respect to the other gyrodactylids, rather than the supposedly ‘primitive’ AfricanMacrogyrodactylus. Inclusion of the AfricanGyrodactylus nyanzaeconfirms the paraphyly ofGyrodactylus. The position of the African dactylogyridCichlidogyrusis unresolved, although gene order suggests it is closely related to marine ancyrocephalines.

Conclusions

The amount of mitogenomic data available for gyrodactylids and dactylogyrids is increased by roughly one-third. Our study underscores the potential of mitochondrial genes and gene order in flatworm phylogenetics, and of next-generation sequencing for marker development for these non-model helminths for which few primers are available while they constitute a risk to tropical aquaculture.
Conformational footprinting of proteins using a combination of top-down electron transfer dissociation and ion mobility
Authors: Konijnenberg Albert , Li Jinyu , Habchi Johny , Dosnon Marion , Rossetti Giulia , Grandori Rita , Longhi Sonia , Carloni Paolo , Sobott Frank
Published: March 2018

In recent years native mass spectrometry has been increasingly employed to study protein structure. As such a thorough understanding of the effect of the gas-phase on protein structure is becoming increasingly important. We show how a combination of top-down ETD and ion mobility can be used to probe the gas-phase structure of heterogeneous protein ensembles. By applying collisional activation to the non-covalently bound ETD products after IM separation, the peptide fragments can be released while maintaining the conformational information of the protein ion. We studied the unknown gas-phase structures of the measles virus (MeV) phosphoprotein X domain (PXD), which shows a wide range of different conformations in the gas-phase. We then generated structural models by state-of-the-art gas-phase steered molecular dynamics, which we verified using restraints from ion mobility and the fragment patterns observed. Our findings illustrate the applicability of ETD for obtaining conformational specific structural information on heterogeneous protein ensembles.
Genome-wide fitness assessment during diurnal growth reveals an expanded role of the cyanobacterial circadian clock protein KaiA
Authors: Welkie David G. , Rubin Benjamin E. , Chang Yong-Gang , Diamond Spencer , Rifkin Scott A. , LiWang Andy , Golden Susan S.
Published: March 2018

The recurrent pattern of light and darkness generated by Earth’s axial rotation has profoundly influenced the evolution of organisms, selecting for both biological mechanisms that respond acutely to environmental changes and circadian clocks that program physiology in anticipation of daily variations. The necessity to integrate environmental responsiveness and circadian programming is exemplified in photosynthetic organisms such as cyanobacteria, which depend on light-driven photochemical processes. The cyanobacteriumSynechococcus elongatusPCC 7942 is an excellent model system for dissecting these entwined mechanisms. Its core circadian oscillator, consisting of three proteins KaiA, KaiB, and KaiC, transmits time-of-day signals to clock-output proteins, which reciprocally regulate global transcription. Research performed under constant light facilitates analysis of intrinsic cycles separately from direct environmental responses, but does not provide insight into how these regulatory systems are integrated during light-dark cycles. Thus, we sought to identify genes that are specifically necessary in a day-night environment. We screened a dense bar-coded transposon library in both continuous light and daily cycling conditions and compared the fitness consequences of loss of each nonessential gene in the genome. Although the clock itself is not essential for viability in light-dark cycles, the most detrimental mutations revealed by the screen were those that disrupt KaiA. The screen broadened our understanding of light-dark survival in photosynthetic organisms, identified unforeseen clock-protein interaction dynamics, and reinforced the role of the clock as a negative regulator of a night-time metabolic program that is essential forS. elongatusto survive in the dark.

Significance

Understanding how photosynthetic bacteria respond to and anticipate natural light–dark cycles is necessary for predictive modeling, bioengineering, and elucidating metabolic strategies for diurnal growth. Here, we identify the genetic components that are important specifically under light-dark cycling conditions and determine how a properly functioning circadian clock prepares metabolism for darkness, a starvation period for photoautotrophs. This study establishes that the core circadian clock protein KaiA is necessary to enable rhythmic de-repression of a night-time circadian program.