bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting the nutritional quality of feed ingredients for pigs using near-infrared spectroscopy (NIRS) and chemical analysis
Authors: van Barneveld R. J. , Graham H. , Diffey S.
Published: January 2018

Capacity to routinely, accurately and cost-effectively measure variation in the nutritional quality of feed ingredients before diet formulation represents a fundamental pillar of sustainable pork production worldwide. Factors driving sustainable pork production include pork price, feed cost, utilisation of co-products and downgraded raw materials and variation in pork production, with all being related to the definition and ultimate nutritional quality of feed ingredients. The present paper defines rapid measures of nutritional quality in feed ingredients for pigs and demonstrates the range that can exist in these parameters, specifically digestible energy of cereal grains and the reactive-lysine concentration of oilseed meals. It provides an overview of the development of near-infrared spectroscopy (NIRS) calibrations for key nutritional-quality parameters and how they are being applied by the pork industry. Adjunct ways to measure nutritional quality of feed ingredients for pigs such as the glucose-release index and how these can be used in conjunction with NIRS are reviewed. The paper reports advanced correlation analysis between chemical components and digestible-energy concentration of cereals, and how these could be used for screening of NIRS outliers, and discusses future opportunities for application of nutritional-quality analysis using NIRS calibrations, including feed intake and portable solutions. Using advanced NIRS calibrations for digestible energy in cereals and reactive lysine in oilseed meals, pork producers will ensure that they make best use of limited resources and, as a consequence, pork will remain a nutritionally accretive food source for increasingly discerning consumers worldwide.
Global extent and distribution of wetlands: trends and issues
Authors: Davidson N. C. , Fluet-Chouinard E. , Finlayson C. M.
Published: January 2018

Herein we review estimates of global and regional wetland area from ‘bottom-up’ approaches of site or national wetland inventories and ‘top-down’ approaches from global mapping and remote sensing. The trend for increasing wetland extent reported in the literature over time is a consequence of improved mapping technologies and methods rather than a real increase in wetland area, because a continuing trend for natural wetland loss and conversion is documented over the same time period. The most recent high-resolution estimate of global wetland area is in excess of 12.1×106km2, of which 54% is permanently inundated and 46% is temporarily inundated. Globally, 92.8% of continental wetland area is inland and only 7.2% is coastal. Regionally, the largest wetland areas are in Asia (31.8%), North America (27.1%) and Latin America and the Caribbean (Neotropics; 15.8%), with smaller areas in Europe (12.5%), Africa (9.9%) and Oceania (2.9%). It is likely that estimates of global wetland area published to date persist in underestimating the true wetland area. The ‘grand challenge’ of a global inventory integrating all types of permanent and temporary wetlands at high spatial resolution has yet to be fully achieved.
Creative entextualizations of discourses about race in multi-sited discursive practices in the Brazilian ‘periphery’
Authors: Guimarães Thayse Figueira , Moita-Lopes Luiz Paulo
Published: January 2018

This paper focuses on Luan’s race performances both on the web and in classroom interaction. Luan is a black young man, who identifies himself as gay. The study is part of a multi-sited ethnographic piece of research on a group of high-school students in the state sector, in the ‘periphery’ of a town on the Rio de Janeiro State north coast, Brazil. The paper is guided by performance and entextualization theorizing. The analysis draws attention to the circulation of racial identity signs, intersected with gender/sexuality meanings, bringing to light what we call creative entextualizations, i.e. the gaps Luan finds to re-organize the meanings in the discursive practices in which he is engaged. The analyses point to positionings and innovative identity performances which come up in conjunction with essentialized views, always perceptible amidst struggles and disputes. Because it draws attention to mobile lives in the ‘periphery’, this study may be said to explode the traditional boundaries between ‘center’ and ‘periphery’.
A Note on the 2017 Landmark US Ruling on the Constitutionality of Prohibiting the Trademarking of Potentially Disparaging Names
Authors: Nick I. M.
Published: January 2018

The Lanham Act was enacted by the US Congress in 1946 with the overall purpose of regularizing the nation’s registration and use of trademarks. Despite undergoing a number of amendments since its enactment, for the past 70 years, the Act has continued to provide key federal protections against not only the unlawful or deceptive use of trademarks. It also strictly forbad the registration of marks that reasonably could be considered immoral, scandalous, contemptuous, or disparaging. Though hailed by some as an important protection against hateful speech in the public marketplace, others have questioned whether the statute violates the constitutional right to Freedom of Speech. This year, the US Supreme Court issued a ruling that put an official end to this legal controversy. This article provides a detailed description of the case that led to this landmark decision and discusses some of the potential implications for trademarking potentially disparaging brand names.
An interaction between myosin-10 and the cell cycle regulator Wee1 links spindle dynamics to mitotic progression in epithelia
Authors: Sandquist Joshua C. , Larson Matthew E. , Woolner Sarah , Ding Zhiwei , Bement William M.
Published: January 2018

Anaphase in epithelia typically does not ensue until after spindles have achieved a characteristic position and orientation, but how or even if cells link spindle position to anaphase onset is unknown. Here, we show that myosin-10 (Myo10), a motor protein involved in epithelial spindle dynamics, binds to Wee1, a conserved regulator of cyclin-dependent kinase 1 (Cdk1). Wee1 inhibition accelerates progression through metaphase and disrupts normal spindle dynamics, whereas perturbing Myo10 function delays anaphase onset in a Wee1-dependent manner. Moreover, Myo10 perturbation increases Wee1-mediated inhibitory phosphorylation on Cdk1, which, unexpectedly, concentrates at cell–cell junctions. Based on these and other results, we propose a model in which the Myo10–Wee1 interaction coordinates attainment of spindle position and orientation with anaphase onset.
A model-free method for measuring dimerization free energies of CLC-ec1 in lipid bilayers
Authors: Chadda Rahul , Cliff Lucy , Brimberry Marley , Robertson Janice L.
Published: January 2018

The thermodynamic reasons why membrane proteins form stable complexes inside the hydrophobic lipid bilayer remain poorly understood. This is largely because of a lack of membrane–protein systems amenable for equilibrium studies and a limited number of methods for measuring these reactions. Recently, we reported the equilibrium dimerization of the CLC-ec1 Cl−/H+ transporter in lipid bilayers (Chadda et al. 2016. eLife. https://doi.org/10.7554/eLife.17438), which provided a new type of model system for studying protein association in membranes. The measurement was conducted using the subunit-capture approach, involving passive dilution of the protein in large multilamellar vesicles, followed by single-molecule photobleaching analysis of the Poisson distribution describing protein encapsulation into extruded liposomes. To estimate the fraction of dimers (FDimer) as a function of protein density, the photobleaching distributions for the nonreactive, ideal monomer and dimer species must be known so that random co-capture probabilities can be accounted for. Previously, this was done by simulating the Poisson process of protein reconstitution into a known size distribution of liposomes composed of Escherichia coli polar lipids (EPLs). In the present study, we investigate the dependency of FDimer and ΔG° on the modeling through a comparison of different liposome size distributions (EPL versus 2:1 POPE/POPG). The results show that the estimated FDimer values are comparable, except at higher densities when liposomes become saturated with protein. We then develop empirical controls to directly measure the photobleaching distributions of the nonreactive monomer (CLC-ec1 I201W/I422W) and ideal dimer (WT CLC-ec1 cross-linked by glutaraldehyde or CLC-ec1 R230C/L249C cross-linked by a disulfide bond). The measured equilibrium constants do not depend on the correction method used, indicating the robustness of the subunit-capture approach. This strategy therefore presents a model-free way to quantify protein dimerization in lipid bilayers, offering a simplified strategy in the ongoing effort to characterize equilibrium membrane–protein reactions in membranes.
Estimating kinetic mechanisms with prior knowledge I: Linear parameter constraints
Authors: Salari Autoosa , Navarro Marco A. , Milescu Mirela , Milescu Lorin S.
Published: January 2018

To understand how ion channels and other proteins function at the molecular and cellular levels, one must decrypt their kinetic mechanisms. Sophisticated algorithms have been developed that can be used to extract kinetic parameters from a variety of experimental data types. However, formulating models that not only explain new data, but are also consistent with existing knowledge, remains a challenge. Here, we present a two-part study describing a mathematical and computational formalism that can be used to enforce prior knowledge into the model using constraints. In this first part, we focus on constraints that enforce explicit linear relationships involving rate constants or other model parameters. We develop a simple, linear algebra–based transformation that can be applied to enforce many types of model properties and assumptions, such as microscopic reversibility, allosteric gating, and equality and inequality parameter relationships. This transformation converts the set of linearly interdependent model parameters into a reduced set of independent parameters, which can be passed to an automated search engine for model optimization. In the companion article, we introduce a complementary method that can be used to enforce arbitrary parameter relationships and any constraints that quantify the behavior of the model under certain conditions. The procedures described in this study can, in principle, be coupled to any of the existing methods for solving molecular kinetics for ion channels or other proteins. These concepts can be used not only to enforce existing knowledge but also to formulate and test new hypotheses.
Estimating kinetic mechanisms with prior knowledge II: Behavioral constraints and numerical tests
Authors: Navarro Marco A. , Salari Autoosa , Milescu Mirela , Milescu Lorin S.
Published: January 2018

Kinetic mechanisms predict how ion channels and other proteins function at the molecular and cellular levels. Ideally, a kinetic model should explain new data but also be consistent with existing knowledge. In this two-part study, we present a mathematical and computational formalism that can be used to enforce prior knowledge into kinetic models using constraints. Here, we focus on constraints that quantify the behavior of the model under certain conditions, and on constraints that enforce arbitrary parameter relationships. The penalty-based optimization mechanism described here can be used to enforce virtually any model property or behavior, including those that cannot be easily expressed through mathematical relationships. Examples include maximum open probability, use-dependent availability, and nonlinear parameter relationships. We use a simple kinetic mechanism to test multiple sets of constraints that implement linear parameter relationships and arbitrary model properties and behaviors, and we provide numerical examples. This work complements and extends the companion article, where we show how to enforce explicit linear parameter relationships. By incorporating more knowledge into the parameter estimation procedure, it is possible to obtain more realistic and robust models with greater predictive power.
Antarctic Climate History and Global Climate Changes
Authors: Lurcock Pontus , Florindo Fabio
Published: January 2018

Antarctic climate changes have been reconstructed from ice and sediment cores and numerical models (which also predict future changes). Major ice sheets first appeared 34 million years ago (Ma) and fluctuated throughout the Oligocene, with an overall cooling trend. Ice volume more than doubled at the Oligocene-Miocene boundary. Fluctuating Miocene temperatures peaked at 17–14 Ma, followed by dramatic cooling. Cooling continued through the Pliocene and Pleistocene, with another major glacial expansion at 3–2 Ma. Several interacting drivers control Antarctic climate. On timescales of 10,000–100,000 years, insolation varies with orbital cycles, causing periodic climate variations. Opening of Southern Ocean gateways produced a circumpolar current that thermally isolated Antarctica. Declining atmospheric CO2 triggered Cenozoic glaciation. Antarctic glaciations affect global climate by lowering sea level, intensifying atmospheric circulation, and increasing planetary albedo. Ice sheets interact with ocean water, forming water masses that play a key role in global ocean circulation.
Food, the Environment, and Global Justice
Authors: Budolfson Mark
Published: January 2018

This chapter identifies and critically examines a standard form of argument for organic and vegan alternatives to industrial agriculture. This argument faces important objections to its empirical premises, to its presumption that there is a single food system that minimizes harm and is best for the environment, and to the presumption that the ethically best food system for us to promote is the one that would be best in ideal theory or the one that would be best from the perspective of our own society. Instead, determining which food system should be promoted arguably requires a complex global, empirical, and ethical integrated assessment that includes a proper accounting for values of global justice in nonideal theory. This proper accounting arguably recommends sustainable intensification of food systems (as it is called in the food-science literature), which is importantly distinct from contemporary systems as well as from organic, local, and/or vegan-centered alternatives.
Effective Inpatient and Outpatient Models of Treatment for Adolescents With Substance Use Disorders
Authors: Pugatch Marianne , Knight John R. , Copelas Sarah , Buynitsky Tatiana , Boyd J. Wesley
Published: January 2018

This chapter provides an overview of the physical, psychological, and brain development of the adolescent, establishing the need for treatment tailored to their unique developmental needs. It also defines the goals and phases of treatment, describes the continuum of care and contextualizes the body of effectiveness treatment research. The chapter reviews the evidence based literature on inpatient and outpatient settings including short-term detoxification, acute and long-term residential care, sober houses, therapeutic schools, day hospitals, intensive outpatient as well as outpatient approaches. Overall, studies indicate that treatment in youth has small to moderate effects. The chapter concludes with recommendations for what professionals and parents should look for in treatment programs for adolescent clients and discusses future research and policy recommendations.
Patterns of Disrespectful Physician Behavior at an Academic Medical Center: Implications for Training, Prevention, and Remediation
Authors: Hopkins Joseph , Hedlin Haley , Weinacker Ann , Desai Manisha
Published: January 2018

Purpose

Physician disrespectful behavior affects quality of care, patient safety, and collaborative clinical team function. Evidence defining the demographics, ethnography, and epidemiology of disrespectful behavior is lacking.

Method

The authors conducted a retrospective analysis of reports of disrespectful physician behavior at Stanford Hospital and Clinics from March 2011 through February 2015. Events were stratified by role, gender, specialty, and location in the hospital or clinics where the event occurred. Event rate ratios were estimated using a multivariable negative binomial regression model. Correlation of rates of faculty and trainees in the same specialty was assessed.

Results

One hundred ninety-nine events concerned faculty; 160 concerned trainees. Events were concentrated among a small number of physicians in both groups. The rates of faculty and trainee events within the same specialty were highly correlated (Spearman’s rho: 0.90; P < .001). Male physicians had an adjusted event rate 1.86 (95% CI = 1.33–2.60; P < .001) times that of females. Procedural physicians were 3.67 times (95% CI = 2.63–5.13; P < .001) more likely to have a disrespectful behavior event than nonprocedural physicians when adjusting for other covariates. Most common location for faculty was the operating rooms (69 events, 34%); for trainees, the medical/surgical units (43 events, 27%).

Conclusions

Patterns of physician disrespectful behavior differed by role, gender, specialty, and location. Rates among faculty and trainees of the same specialty were highly correlated. These patterns can be used to create more focused education and training for specific physician groups and individualized remediation interventions.
Oligorecurrent Nodal Prostate Cancer
Authors: Tran Sebastien , Jorcano Sandra , Falco Teresa , Lamanna Giorgio , Miralbell Raymond , Zilli Thomas
Published: January 2018

Objectives:

The objective of this study was to report long-term results of elective nodal radiotherapy (ENRT) in prostate cancer (PCa) patients with oligorecurrent nodal disease after primary treatment.

Methods:

Data of 53 oligorecurrent PCa patients (N1 and/or M1a) with ≤5 nodal metastases (n=108) treated with ENRT combined with androgen deprivation therapy (ADT) between 2004 and 2016 were retrospectively reviewed. Median prostate-specific antigen (PSA) and PSA doubling time (DT) were 3.4 ng/mL and 5 months, respectively. At restaging, 45% of the patients presented single nodal metastases, mainly located in the pelvis (n=38). All patients underwent ENRT between 45 and 50.4 Gy with a boost on positive nodes (median 64.4 Gy; 54 to 69 Gy) using mainly VMAT (n=24) or IMRT (n=21) techniques. Concomitant ADT was administered to all patients for a median time of 6 months.

Results:

After a median follow-up after ENRT of 44 months (range, 2 to 133), the 5-year biochemical disease-free and distant progression-free survival (DPFS) rates were 43% and 58%, respectively, with worse DPFS observed in patients with a PSA-doubling time <3 months (36.8% vs. 63.6%; P=0.029). Seventeen of 19 clinically relapsing patients presented lesions out of the ENRT field, and 10 were again oligometastatic. Only 2 patients presented with a CTCAE v3.0 grade ≥2 genitourinary toxicity.

Conclusions:

ENRT combined with short-course ADT is a safe and effective salvage modality for patients with oligorecurrent nodal PCa. Prospective randomized studies comparing focal SBRT versus ENRT are warranted to define the best treatment strategy.
State-based Review of Maternal Deaths: The Ohio Experience
Authors: SHELLHAAS CYNTHIA , CONREY ELIZABETH
Published: January 2018

Ohio established a Pregnancy-Associated Mortality Review system in 2010 to ensure that all maternal deaths are identified and preventive actions developed. The need for detailed and reliable information to supplement vital statistics data has led to the development of state-based and urban-based maternal death reviews. Although processes vary from state to state, in general, an expert panel is convened to review individual cases and make recommendations for systems change. This article describes the development and operation of Ohio’s state-based maternal death review including interventions developed and actions taken based on review data.
Longitudinal resting-state functional magnetic resonance imaging in a mouse model of metastatic bone cancer reveals distinct functional reorganizations along a developing chronic pain state
Authors: Buehlmann David , Grandjean Joanes , Xandry Jael , Rudin Markus
Published: January 2018

Functional neuroimaging has emerged as attractive option for characterizing pain states complementing behavioral readouts or clinical assessment. In particular, resting-state functional magnetic resonance imaging (rs-fMRI) enables monitoring of functional adaptations across the brain, for example, in response to chronic nociceptive input. We have used rs-fMRI in a mouse model of chronic pain from breast cancer–derived tibial bone metastases to identify pain-induced alterations in functional connectivity. Combined assessment of behavioral readouts allowed for defining a trajectory as model function for extracting pain‐specific functional connectivity changes from the fMRI data reflective of a chronic pain state. Cingulate and prefrontal cortices as well as the ventral striatum were identified as predominantly affected regions, in line with findings from clinical and preclinical studies. Inhibition of the peripheral bone remodeling processes by antiosteolytic therapy led to a reduction of pain-induced network alterations, emphasizing the specificity of the functional readouts for a developing chronic pain state.
Role of GPCR (mu-opioid)–receptor tyrosine kinase (epidermal growth factor) crosstalk in opioid-induced hyperalgesic priming (type II)
Authors: Araldi Dionéia , Ferrari Luiz F. , Levine Jon D.
Published: January 2018

Repeated stimulation of mu-opioid receptors (MORs), by an MOR-selective agonist DAMGO induces type II priming, a form of nociceptor neuroplasticity, which has 2 components: opioid-induced hyperalgesia (OIH) and prolongation of prostaglandin-E2 (PGE2)-induced hyperalgesia. We report that intrathecal antisense knockdown of the MOR in nociceptors, prevented the induction of both components of type II priming. Type II priming was also eliminated by SSP-saporin, which destroys the peptidergic class of nociceptors. Because the epidermal growth factor receptor (EGFR) participates in MOR signaling, we tested its role in type II priming. The EGFR inhibitor, tyrphostin AG 1478, prevented the induction of prolonged PGE2-induced hyperalgesia, but not OIH, when tested out to 30 days after DAMGO. However, even when repeatedly injected, an EGFR agonist did not induce hyperalgesia or priming. A phosphopeptide, which blocks the interaction of Src, focal adhesion kinase (FAK), and EGFR, also prevented DAMGO-induced prolongation of PGE2 hyperalgesia, but only partially attenuated the induction of OIH. Inhibitors of Src and mitogen-activated protein kinase (MAPK) also only attenuated OIH. Inhibitors of matrix metalloproteinase, which cleaves EGF from membrane protein, markedly attenuated the expression, but did not prevent the induction, of prolongation of PGE2 hyperalgesia. Thus, although the induction of prolongation of PGE2-induced hyperalgesia at the peripheral terminal of peptidergic nociceptor is dependent on Src, FAK, EGFR, and MAPK signaling, Src, FAK, and MAPK signaling is only partially involved in the induction of OIH.
Percutaneous endoscopic gastrostomy with and without jejunal extension in patients with amyotrophic lateral sclerosis
Authors: Kirstein Martha M. , Körner Sonja , Schneider Andrea , Manns Michael P. , Petri Susanne , Voigtländer Torsten
Published: January 2018

Background and aims

Amyotrophic lateral sclerosis (ALS) is a fatal degenerative disease of the motor nervous system, which is associated with severe loss of weight. Enteral nutrition through percutaneous endoscopic gastrostomy (PEG) or percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) is generally recommended upon disease progression. There is no standard endoscopic method that should preferentially be performed. The aim of this study was to compare the number of adverse events, complication-free survival (CFS), and overall survival (OS) in patients who received PEG or PEG-J.

Patients and methods

All patients with ALS presenting for PEG or PEG-J placement to the Endoscopic Unit of Hannover Medical School, Germany, between 2009 and 2015 were retrospectively analyzed.

Results

Demographics were similar for patients receiving PEG (n=43) and PEG-J (n=39). The median intervention time and the absolute dose of propofol were significantly longer and, respectively, higher for patients with PEG-J (P=0.001 and 0.013). Intervention-related complications leading to hospitalization were significantly more frequent in patients who received PEG-J (36 vs. 4, P=0.001). The median CFS was significantly shorter in patients who received PEG-J compared with PEG (5 vs. 14 months, P=0.007). There was no difference in OS.

Conclusion

Intervention-related complications were more frequent and the median CFS was shorter in patients who received PEG-J, whereas there was no difference in OS. Given the poor prognosis of patients with ALS, our data provide first evidence that PEG might be the better tolerable option, with fewer complications. The decision on which nutritional system is implanted should be evaluated individually.
Epstein-Barr Virus (EBV)-induced B-cell Lymphoproliferative Disorder Mimicking the Recurrence of EBV-associated Hemophagocytic Lymphohistiocytosis
Authors: Yatsushiro Yuki , Nishikawa Takuro , Saito Aki , Nakazawa Yozo , Imadome Ken-Ichi , Nakagawa Shunsuke , Kodama Yuichi , Okamoto Yasuhiro , Kanegane Hirokazu , Kawano Yoshifumi
Published: January 2018

We describe the case of a 23-month-old male infant with Epstein-Barr virus (EBV)-associated lymphoproliferative disorder, which mimicked the recurrence of EBV-associated hemophagocytic lymphohistiocytosis. Chemotherapy with dexamethasone, etoposide, and cyclosporine resolved fever, hepatosplenomegaly, and pancytopenia. However, on day 81 of illness, the patient developed similar symptoms. Plasma EBV-DNA levels markedly increased again, but no T-cell clonality was observed. B cells were identified to be infected with EBV. He was successfully treated with rituximab, dexamethasone and etoposide. When recurrence of EBV-associated hemophagocytic lymphohistiocytosis is suspected, performing tests to identify the infected cells will enable accurate understanding of the clinical condition, resulting in proper treatments.
Low-Dose Epinephrine Boluses for Acute Hypotension in the PICU*
Authors: Reiter Pamela D. , Roth Jennifer , Wathen Beth , LaVelle Jaime , Ridall Leslie A.
Published: January 2018

Objectives:

To describe the use of low-dose bolus epinephrine in critically ill children during an acute hypotensive episode or prearrest condition.

Design:

Institutional Review Board approved, single-center, retrospective medical chart review.

Setting:

Large medical-surgical PICU within a freestanding, tertiary care children’s hospital.

Patients:

Patients admitted to the PICU between June 1, 2015, and June 1, 2016, who received low-dose (≤ 5 µg/kg) IV bolus epinephrine.

Interventions:

None.

Measurement and Main Results:

Twenty-four resuscitation episodes (63 doses; 19 patients) were analyzed. Median age and weight of patients were 9 years (interquartile range, 1–15 yr) and 38.5 kg (interquartile range, 12–54.8 kg). Median Pediatric Risk of Mortality III score was 17 (interquartile range, 10–27). Mean epinephrine dose was 1.3 ± 1.1 µg/kg. Median number of doses per patient was two. If more than one dose was provided, median dosing interval was 6.5 minutes. Heart rate and mean arterial blood pressure were compared at the time of epinephrine administration and 1–4 minutes (median = 1 min) following administration. Heart rate changed from 130 ± 41 to 150 ± 33 beats/min (p < 0.05), and mean arterial blood pressure changed from 51 ± 17 to 75 ± 27 mm Hg (p < 0.001). Variability in mean arterial blood pressure response was observed; nonresponders required extracorporeal membrane oxygenation; 66% of doses resulted in up to 100% mean arterial blood pressure increase, and 21% of doses resulted in greater than 100% mean arterial blood pressure increase. Doses below 1 µg/kg were associated with a lower mean arterial blood pressure increase than doses between 1 and 5 µg/kg (mean percent change in mean arterial blood pressure = 6.6% vs 60%, respectively). Children less than or equal to 2 years old had the greatest percentage increase in heart rate and mean arterial blood pressure.

Conclusions:

Provision of low-dose bolus epinephrine during periods of acute hypotension can result in a significant increase in mean arterial blood pressure and heart rate. This dosing strategy may provide temporary stabilization while other therapies are added or adjusted, but further research is needed.
Supported self-management for cancer survivors to address long-term biopsychosocial consequences of cancer and treatment to optimize living well
Authors: Howell Doris D.
Published: January 2018

Purpose of review

As individuals are living longer with cancer as a chronic disease, they face new health challenges that require the application of self-management behaviors and skills that may not be in their usual repertoire of self-regulatory health behaviors. Increasing attention is focused on supported self-management (SSM) programs to enable survivors in managing the long-term biopsychosocial consequences and health challenges of survivorship. This review explores current directions and evidence for SSM programs that enable survivors to manage these consequences and optimize health.

Recent findings

Cancer survivors face complex health challenges that affect daily functioning and well being. Multiple systematic reviews show that SSM programs have positive effects on health outcomes in typical chronic diseases. However, the efficacy of these approaches in cancer survivors are in their infancy; and the ‘one-size’ fits all approach for chronic disease self-management may not be adequate for cancer as a complex chronic illness. This review suggests that SSM has promising potential for improving health and well being of cancer survivors, but there is a need for standardizing SSM for future research.

Although there is increasing enthusiasm for SSM programs tailored to cancer survivors, there is a need for further research of their efficacy on long-term health outcomes.
The MoCA-Memory Index Score
Authors: Kaur Antarpreet , Edland Steven D. , Peavy Guerry M.
Published: January 2018

Objective:

To compare ability of 2 measures of delayed memory (word list, story paragraph) to discriminate Normal Control (NC) subjects from those with amnestic mild cognitive impairment (aMCI).

Methods:

Demographic, neuropsychological, and diagnostic data contributed by 34 Alzheimer’s Disease Centers to the National Alzheimer’s Coordinating Center characterized 2717 individuals with a diagnosis of either NC (n=2205) or aMCI (n=512). The Montreal Cognitive Assessment-Memory Index Score (MoCA-MIS) assessed delayed word recall, and the Craft Story 21, delayed story recall. Logistic regression and receiver operator characteristic curves controlling for age, sex, and education assessed the ability of each test to differentiate NCs from subjects with aMCI.

Results:

The MoCA-MIS had significantly better sensitivity and specificity (area under the receiver operator characteristic curve 0.83 vs. 0.80, P=0.004). At sensitivity 80%, the specificity of the MoCA-MIS was 69.1%, compared with 62.8% for the Craft Story.

Conclusions:

These data suggest that the MoCA-MIS, a recall score from items within the MoCA, is better at discriminating NCs from subjects with aMCI than the Craft Story. Word recall may be an efficient alternative to paragraph recall for diagnostic screening within clinical practice and research settings.
HINTS in the Acute Vestibular Syndrome: Pearls and Pitfalls
Authors: Kung Nathan H. , Van Stavern Gregory P. , Gold Daniel R.
Published: January 2018

The acute vestibular syndrome (AVS) is characterized by the rapid onset of vertigo, nausea/vomiting, nystagmus, unsteady gait, and head motion intolerance lasting more than 24 hours. We present 4 patients with AVS to illustrate the pearls and pitfalls of the Head Impulse, Nystagmus, Test of Skew (HINTS) examination.
Facing each other: mammal mothers and infants prefer the position favouring right hemisphere processing
Authors: Giljov Andrey , Karenina Karina , Malashichev Yegor
Published: January 2018

The right hemisphere plays a crucial role in social processing. Human mothers show a robust left cradling/holding bias providing greater right-hemispheric involvement in the exchange of social information between mother and infant. Here, we demonstrate that a similar bias is evident in face-to-face spatial interactions in marine and terrestrial non-primate mammals. Walruses and Indian flying foxes showed a significant population-level preference for the position which facilitates the use of the left visual field in both mother and infant. This behavioural lateralization may have emerged owing to benefits conferred by the enhanced right-hemispheric social processing providing the mother and infant an optimal perception of each other.
Adding levels of complexity enhances robustness and evolvability in a multilevel genotype–phenotype map
Authors: Catalán Pablo , Wagner Andreas , Manrubia Susanna , Cuesta José A.
Published: January 2018

Robustness and evolvability are the main properties that account for the stability and accessibility of phenotypes. They have been studied in a number of computational genotype–phenotype maps. In this paper, we study a metabolic genotype–phenotype map defined in
toyLIFE
, a multilevel computational model that represents a simplified cellular biology.
toyLIFE
includes several levels of phenotypic expression, from proteins to regulatory networks to metabolism. Our results show that
toyLIFE
shares many similarities with other seemingly unrelated computational genotype–phenotype maps. Thus,
toyLIFE
shows a high degeneracy in the mapping from genotypes to phenotypes, as well as a highly skewed distribution of phenotypic abundances. The neutral networks associated with abundant phenotypes are highly navigable, and common phenotypes are close to each other in genotype space. All of these properties are remarkable, as
toyLIFE
is built on a version of the HP protein-folding model that is neither robust nor evolvable: phenotypes cannot be mutually accessed through point mutations. In addition, both robustness and evolvability increase with the number of genes in a genotype. Therefore, our results suggest that adding levels of complexity to the mapping of genotypes to phenotypes and increasing genome size enhances both these properties.
Contribution of low-temperature single-molecule techniques to structural issues of pigment–protein complexes from photosynthetic purple bacteria
Authors: Löhner Alexander , Cogdell Richard , Köhler Jürgen
Published: January 2018

As the electronic energies of the chromophores in a pigment–protein complex are imposed by the geometrical structure of the protein, this allows the spectral information obtained to be compared with predictions derived from structural models. Thereby, the single-molecule approach is particularly suited for the elucidation of specific, distinctive spectral features that are key for a particular model structure, and that would not be observable in ensemble-averaged spectra due to the heterogeneity of the biological objects. In this concise review, we illustrate with the example of the light-harvesting complexes from photosynthetic purple bacteria how results from low-temperature single-molecule spectroscopy can be used to discriminate between different structural models. Thereby the low-temperature approach provides two advantages: (i) owing to the negligible photobleaching, very long observation times become possible, and more importantly, (ii) at cryogenic temperatures, vibrational degrees of freedom are frozen out, leading to sharper spectral features and in turn to better resolved spectra.
Computational techniques for ECG analysis and interpretation in light of their contribution to medical advances
Authors: Lyon Aurore , Mincholé Ana , Martínez Juan Pablo , Laguna Pablo , Rodriguez Blanca
Published: January 2018

Widely developed for clinical screening, electrocardiogram (ECG) recordings capture the cardiac electrical activity from the body surface. ECG analysis can therefore be a crucial first step to help diagnose, understand and predict cardiovascular disorders responsible for 30% of deaths worldwide. Computational techniques, and more specifically machine learning techniques and computational modelling are powerful tools for classification, clustering and simulation, and they have recently been applied to address the analysis of medical data, especially ECG data. This review describes the computational methods in use for ECG analysis, with a focus on machine learning and 3D computer simulations, as well as their accuracy, clinical implications and contributions to medical advances. The first section focuses on heartbeat classification and the techniques developed to extract and classify abnormal from regular beats. The second section focuses on patient diagnosis from whole recordings, applied to different diseases. The third section presents real-time diagnosis and applications to wearable devices. The fourth section highlights the recent field of personalized ECG computer simulations and their interpretation. Finally, the discussion section outlines the challenges of ECG analysis and provides a critical assessment of the methods presented. The computational methods reported in this review are a strong asset for medical discoveries and their translation to the clinical world may lead to promising advances.
Comparative genomic analysis of the ‘pseudofungus’Hyphochytrium catenoides
Authors: Leonard Guy , Labarre Aurélie , Milner David S. , Monier Adam , Soanes Darren , Wideman Jeremy G. , Maguire Finlay , Stevens Sam , Sain Divya , Grau-Bové Xavier , Sebé-Pedrós Arnau , Stajich Jason E. , Paszkiewicz Konrad , Brown Matthew W. , Hall Neil , Wickstead Bill , Richards Thomas A.
Published: January 2018

Eukaryotic microbes have three primary mechanisms for obtaining nutrients and energy: phagotrophy, photosynthesis and osmotrophy. Traits associated with the latter two functions arose independently multiple times in the eukaryotes. The Fungi successfully coupled osmotrophy with filamentous growth, and similar traits are also manifested in the Pseudofungi (oomycetes and hyphochytriomycetes). Both the Fungi and the Pseudofungi encompass a diversity of plant and animal parasites. Genome-sequencing efforts have focused on host-associated microbes (mutualistic symbionts or parasites), providing limited comparisons with free-living relatives. Here we report the first draft genome sequence of a hyphochytriomycete ‘pseudofungus’;Hyphochytrium catenoides. Using phylogenomic approaches, we identify genes of recent viral ancestry, with related viral derived genes also present on the genomes of oomycetes, suggesting a complex history of viral coevolution and integration across the Pseudofungi.H. catenoideshas a complex life cycle involving diverse filamentous structures and a flagellated zoospore with a single anterior tinselate flagellum. We use genome comparisons, drug sensitivity analysis and high-throughput culture arrays to investigate the ancestry of oomycete/pseudofungal characteristics, demonstrating that many of the genetic features associated with parasitic traits evolved specifically within the oomycete radiation. Comparative genomics also identified differences in the repertoire of genes associated with filamentous growth between the Fungi and the Pseudofungi, including differences in vesicle trafficking systems, cell-wall synthesis pathways and motor protein repertoire, demonstrating that unique cellular systems underpinned the convergent evolution of filamentous osmotrophic growth in these two eukaryotic groups.
A glimpse of an ancient agricultural ecosystem based on remains of micromammals in the Byzantine Negev Desert
Authors: Fried Tal , Weissbrod Lior , Tepper Yotam , Bar-Oz Guy
Published: January 2018

It is widely believed that Byzantine agriculture in the Negev Desert (fourth to seventh century Common Era; CE), with widespread construction of terraces and dams, altered local landscapes. However, no direct evidence in archaeological sites yet exists to test this assumption. We uncovered large amounts of small mammalian remains (rodents and insectivores) within agricultural installations built near fields, providing a new line of evidence for reconstructing anthropogenic impact on local habitats. Abandonment layers furnished high abundances of remains, whereas much smaller numbers were retrieved from the period of human use of the structures. Digestion marks are present in low frequencies (20% of long bones and teeth), with a light degree of impact, which indicate the role of owls (e.g.Tyto alba) as the principal means of accumulation. The most common taxa—gerbils (Gerbillusspp.) and jirds (Merionesspp.)—occur in nearly equal frequencies, which do not correspond with any modern Negev communities, where gerbils predominate in sandy low-precipitation environments and jirds in loessial, higher-precipitation ones. Although low-level climate change cannot be ruled out, the results suggest that Byzantine agriculture allowed jirds to colonize sandy anthropogenic habitats with other gerbilids and commensal mice and rats.
Atlantic bluefin tuna spawn at suboptimal temperatures for their offspring
Authors: Reglero P. , Ortega A. , Balbín R. , Abascal F. J. , Medina A. , Blanco E. , de la Gándara F. , Alvarez-Berastegui D. , Hidalgo M. , Rasmuson L. , Alemany F. , Fiksen Ø.
Published: January 2018

Life-history traits such as spawning migrations and timing of reproduction are adaptations to specific environmental constraints and seasonal cycles in many organisms' annual routines. In this study we analyse how offspring fitness constrains spawning phenology in a large migratory apex predator, the Atlantic bluefin tuna. The reproductive schedule of Atlantic bluefin tuna varies between spawning sites, suggesting plasticity to local environmental conditions. Generally, temperature is considered to be the main constraint on tuna spawning phenology. We combine evidence from long-term field data, temperature-controlled rearing experiments on eggs and larvae, and a model of egg fitness, and show that Atlantic bluefin tuna do not spawn to optimize egg and larval temperature exposure. The timing of spawning leads to temperature exposure considerably lower than optimal at all spawning grounds across the Atlantic Ocean. The early spawning is constrained by thermal inhibition of egg hatching and larval growth rates, but some other factors must prevent later spawning. Matching offspring with ocean productivity and the prey peak might be an important driver for bluefin tuna spawning phenology. This finding is important for predictions of reproductive timing in future climate warming scenarios for bluefin tuna.
Substrate growth dynamics and biomineralization of an Ediacaran encrusting poriferan
Authors: Wood Rachel , Penny Amelia
Published: January 2018

The ability to encrust in order to secure and maintain growth on a substrate is a key competitive innovation in benthic metazoans. Here we describe the substrate growth dynamics, mode of biomineralization and possible affinity ofNamapoikia rietoogensis, a large (up to 1 m), robustly skeletal, and modular Ediacaran metazoan which encrusted the walls of synsedimentary fissures within microbial–metazoan reefs.Namapoikiaformed laminar or domal morphologies with an internal structure of open tubules and transverse elements, and had a very plastic, non-deterministic growth form which could encrust both fully lithified surfaces as well as living microbial substrates, the latter via modified skeletal holdfasts.Namapoikiashows complex growth interactions and substrate competition with contemporary living microbialites and thrombolites, including the production of plate-like dissepiments in response to microbial overgrowth which served to elevate soft tissue above the microbial surface.Namapoikiacould also recover from partial mortality due to microbial fouling. We infer initial skeletal growth to have propagated via the rapid formation of an organic scaffold via a basal pinacoderm prior to calcification. This is likely an ancient mode of biomineralization with similarities to the living calcified demospongeVaceletia. Namapoikiaalso shows inferred skeletal growth banding which, combined with its large size, implies notable individual longevity. In sum,Namapoikiawas a large, relatively long-lived Ediacaran clonal skeletal metazoan that propagated via an organic scaffold prior to calcification, enabling rapid, effective and dynamic substrate occupation and competition in cryptic reef settings. The open tubular internal structure, highly flexible, non-deterministic skeletal organization, and inferred style of biomineralization ofNamapoikiaplaces probable affinity within total-group poriferans.
Characterization ofP. falciparumdipeptidyl aminopeptidase 3 specificity reveals structural factors responsible for differences in amino acid preferences between peptide-based substrates and covalent inhibitors
Authors: de Vries Laura E. , Sanchez Mateo I. , Groborz Katarzyna , Kuppens Laurie , Poreba Marcin , Lehmann Christine , Yuan Fang , Arastu-Kapur Shirin , Horn Martin , Mares Michael , Bogyo Matthew , Drag Marcin , Deu Edgar
Published: January 2018

Malarial dipeptidyl aminopeptidases (DPAPs) are cysteine proteases important for parasite development thus making them attractive drug targets. In order to develop inhibitors specific to the parasite enzymes it is necessary to map the determinants of substrate specificity of the parasite enzymes and its mammalian homologue cathepsin C (CatC). Here, we screened peptide-based libraries of substrates and covalent inhibitors to characterize the differences in specificity between parasite DPAPs and CatC, and used this information to develop highly selective DPAP1 and DPAP3 inhibitors. Interestingly, while the primary amino acid specificity of a protease is often used to develop potent inhibitors, we show that equally potent and highly specific inhibitors can be developed based on the sequences of non-optimal peptide substrates. Importantly, analysis of previously published data about the specificity of other proteases also unveiled significant discrepancies in the amino acid preference between substrates and inhibitors. In this article, we also discuss important structural and theoretical reasons that might account for these discrepancies. Overall, this study illustrates that focusing the development of protease inhibitors solely on substrate specificity might overlook important structural features that can be exploited to develop highly potent and selective compounds.
Inhibitors of lysosomal function or serum starvation in control or LAMP2 deficient cells do not modify the cellular levels of Parkinson disease-associated DJ-1/PARK 7 protein
Authors: Sánchez-Lanzas Raúl , Castaño José G.
Published: January 2018

Mutations in PARK7/DJ-1 gene are associated with familial autosomal recessive Parkinson disease. Recently, lysosomes and chaperone mediated autophagy (CMA) has been reported to participate in the degradation of DJ-1/PARK7 protein. Lamp-2A isoform is considered as the lysosomal receptor for the uptake of proteins being degraded by the CMA pathway. We have used several cell lines with disrupted LAMP2 gene expression and their respective control cells to test the possible role of lysosomal degradation and in particular CMA in DJ-1 /PARK7 degradation. Interruption of LAMP-2 expression did not result in an increase of the steady-state protein levels of DJ-1 /PARK7, as it would have been expected. Furthermore, no change in DJ-1 /PARK7 protein levels were observed upon inhibition of lysosomal function with NH4Cl or NH4Cl plus leupeptin, or after activation of CMA by serum starvation for 24h. Accordingly, we have not found any evidence that DJ-1 /PARK7 protein levels are regulated via lysosomal degradation or the CMA pathway.