bluuebunny/crossref_metadata_2025 huggingface dataset:
In situ structural studies of tripeptidyl peptidase II (TPPII) reveal spatial association with proteasomes
Authors: Fukuda Yoshiyuki , Beck Florian , Plitzko Jürgen M. , Baumeister Wolfgang
Published: April 2017

Significance

Tripeptidyl peptidase II (TPPII) is a key player in protein catabolism. It is common among eukaryotes and believed to act downstream of the 26S proteasome. The giant exopeptidase shows a pronounced polymorphism in vitro; that is, its state of assembly is dependent on protein concentration. In situ structural studies by cryo-electron tomography with the Volta phase plate allow assessment of TPPII supramolecuar organization in a physiological setting. Moreover, cryo-electron tomography allows researchers to probe the spatial association of TPPII with proteasomes. This spatial association is consistent with biochemical data suggesting that TPPII acts as a postproteasomal protease. Our results suggest that the spatial association facilitates sequential protein breakdown by physical proximity.
Emerging infectious diseases: A proactive approach
Authors: Bloom David E. , Black Steven , Rappuoli Rino
Published: April 2017

Infectious diseases are now emerging or reemerging almost every year. This trend will continue because a number of factors, including the increased global population, aging, travel, urbanization, and climate change, favor the emergence, evolution, and spread of new pathogens. The approach used so far for emerging infectious diseases (EIDs) does not work from the technical point of view, and it is not sustainable. However, the advent of platform technologies offers vaccine manufacturers an opportunity to develop new vaccines faster and to reduce the investment to build manufacturing facilities, in addition to allowing for the possible streamlining of regulatory processes. The new technologies also make possible the rapid development of human monoclonal antibodies that could become a potent immediate response to an emergency. So far, several proposals to approach EIDs have been made independently by scientists, the private sector, national governments, and international organizations such as the World Health Organization (WHO). While each of them has merit, there is a need for a global governance that is capable of taking a strong leadership role and making it attractive to all partners to come to the same table and to coordinate the global approach.
Industrial Policy, Learning, and Development
Authors: Stiglitz Joseph E.
Published: April 2017

Industrial policies have played an important role in successful economic development in countries. Through these policies, governments intervene in the market’s sectoral allocation of resources and choice of technologies. Earlier industrial policies had a narrow remit and made use of a limited number of instruments. This chapter argues that governments should pursue broader objectives and use a wider range of instruments. In particular, it argues that ‘learning’ (including learning by doing and learning to learn) is central to development, that there are intrinsic market failures associated with learning, and that carefully crafted industrial policies can promote both learning and development.
Modern American women, 1920 to the present
Authors: Ware Susan
Published: April 2017

‘Modern American women, 1920 to the present’ begins with Eleanor Roosevelt, perhaps the twentieth century's most influential and admired American woman. It describes new dilemmas for modern women, who got many of their ideas from the movies, and how gender—as well as class, race, and geography—affected the experience of hard times during the Great Depression. The New Deal's mix of relief programs, stimulus spending, and economic reforms responded to the economic crisis, but it was spending for World War II that solved the problem. The war increased labor opportunities for women. The effects of the Cold War, the civil rights movement, the revival of feminism, and the continuing struggle for equality and diversity are also discussed.
Plague
Authors: McMillen Christian W.
Published: April 2017

The plague is a disease caused by a bacillus, Yersinia pestis, transmitted by the bite of an infected flea. ‘Plague’ identifies three main periods of the pandemic. It first appeared in the sixth century ce with several epidemics in Europe and the Near East lasting until the end of the eight century. The second pandemic—the Black Death—began in 1347 and killed up to half of the continent’s population. The last European outbreak was in Russia in 1770. The third pandemic began in China in 1890 and spread rapidly around the Pacific world. Improved sanitation, isolation, and new antibiotics help, but the plague still exists today.
Improving the performance of minimizers and winnowing schemes
Authors: Marçais Guillaume , Pellow David , Bork Daniel , Orenstein Yaron , Shamir Ron , Kingsford Carl
Published: April 2017

Motivation

The minimizers scheme is a method for selecting k-mers from sequences. It is used in many bioinformatics software tools to bin comparable sequences or to sample a sequence in a deterministic fashion at approximately regular intervals, in order to reduce memory consumption and processing time. Although very useful, the minimizers selection procedure has undesirable behaviors (e.g. too many k-mers are selected when processing certain sequences). Some of these problems were already known to the authors of the minimizers technique, and the natural lexicographic ordering of k-mers used by minimizers was recognized as their origin. Many software tools using minimizers employ ad hoc variations of the lexicographic order to alleviate those issues.

Results

We provide an in-depth analysis of the effect of k-mer ordering on the performance of the minimizers technique. By using small universal hitting sets (a recently defined concept), we show how to significantly improve the performance of minimizers and avoid some of its worse behaviors. Based on these results, we encourage bioinformatics software developers to use an ordering based on a universal hitting set or, if not possible, a randomized ordering, rather than the lexicographic order. This analysis also settles negatively a conjecture (by Schleimer et al.) on the expected density of minimizers in a random sequence.

Availability and Implementation

The software used for this analysis is available on GitHub: https://github.com/gmarcais/minimizers.git.
Integrative deep models for alternative splicing
Authors: Jha Anupama , Gazzara Matthew R , Barash Yoseph
Published: April 2017

Motivation

Advancements in sequencing technologies have highlighted the role of alternative splicing (AS) in increasing transcriptome complexity. This role of AS, combined with the relation of aberrant splicing to malignant states, motivated two streams of research, experimental and computational. The first involves a myriad of techniques such as RNA-Seq and CLIP-Seq to identify splicing regulators and their putative targets. The second involves probabilistic models, also known as splicing codes, which infer regulatory mechanisms and predict splicing outcome directly from genomic sequence. To date, these models have utilized only expression data. In this work, we address two related challenges: Can we improve on previous models for AS outcome prediction and can we integrate additional sources of data to improve predictions for AS regulatory factors.

Results

We perform a detailed comparison of two previous modeling approaches, Bayesian and Deep Neural networks, dissecting the confounding effects of datasets and target functions. We then develop a new target function for AS prediction in exon skipping events and show it significantly improves model accuracy. Next, we develop a modeling framework that leverages transfer learning to incorporate CLIP-Seq, knockdown and over expression experiments, which are inherently noisy and suffer from missing values. Using several datasets involving key splice factors in mouse brain, muscle and heart we demonstrate both the prediction improvements and biological insights offered by our new models. Overall, the framework we propose offers a scalable integrative solution to improve splicing code modeling as vast amounts of relevant genomic data become available.

Availability and implementation

Code and data available at: majiq.biociphers.org/jha_et_al_2017/

Supplementary information

Supplementary data are available at Bioinformatics online.
Expanding the conceptual framework of the spatial population structure and life history of jack mackerel in the eastern South Pacific: an oceanic seamount region as potential spawning/nursery habitat
Authors: Parada Carolina , Gretchina Alexandre , Vásquez Sebastián , Belmadani Ali , Combes Vincent , Ernst Billy , Di Lorenzo Emanuele , Porobic Javier , Sepúlveda Aquiles
Published: April 2017

Juvenile jack mackerel were found in 2009 in the Challenger break and the East Pacific ridge (CHAEPR). This seamount region is ∼3500 km from the coastal historic jack mackerel nursery grounds off Chile (north of 30°S). We reviewed historic evidence of juveniles around this seamount and data on several local environmental conditions: sea surface temperature, chlorophyll-a, wind, turbulence levels, and Eddy kinetic energy (EKE). A Lagrangian model for the early life stages of jack mackerel in the eastern South Pacific was used to assess the potential of the seamount region as a permanent nursery ground. Transport/retention mechanisms were assessed by releasing virtual particles coupled to a growth model into the flow simulated by an eddy-resolving ocean model. Model simulations showed high inter-annual variability for particle retention in the seamount region; high retention levels were associated with low EKE such that the particles were retained for several months. Satellite altimetry has shown a local minimum in eddy activity in the region where the juveniles were observed; this minimum was consistent with the above temporal relationship. The inclusion of the CHAEPR oceanic seamount region as a potential nursery ground for jack mackerel expands the current conceptual framework for the spatial population structure of this species in the South Pacific off central Chile proposed by Arcos et al. (The jack mackerel fishery and El Niño 1997–98 effects off Chile. Progress in Oceanography 49: 597–617, 2001). Finally, we discuss the relevance of seamounts playing a double role (spawning and nursery grounds) from the standpoint of conservation and biodiversity.
Mining e-cigarette adverse events in social media using Bi-LSTM recurrent neural network with word embedding representation
Authors: Xie Jiaheng , Liu Xiao , Dajun Zeng Daniel
Published: April 2017

Objective

Recent years have seen increased worldwide popularity of e-cigarette use. However, the risks of e-cigarettes are underexamined. Most e-cigarette adverse event studies have achieved low detection rates due to limited subject sample sizes in the experiments and surveys. Social media provides a large data repository of consumers’ e-cigarette feedback and experiences, which are useful for e-cigarette safety surveillance. However, it is difficult to automatically interpret the informal and nontechnical consumer vocabulary about e-cigarettes in social media. This issue hinders the use of social media content for e-cigarette safety surveillance. Recent developments in deep neural network methods have shown promise for named entity extraction from noisy text. Motivated by these observations, we aimed to design a deep neural network approach to extract e-cigarette safety information in social media.

Methods

Our deep neural language model utilizes word embedding as the representation of text input and recognizes named entity types with the state-of-the-art Bidirectional Long Short-Term Memory (Bi-LSTM) Recurrent Neural Network.

Results

Our Bi-LSTM model achieved the best performance compared to 3 baseline models, with a precision of 94.10%, a recall of 91.80%, and an F-measure of 92.94%. We identified 1591 unique adverse events and 9930 unique e-cigarette components (ie, chemicals, flavors, and devices) from our research testbed.

Conclusion

Although the conditional random field baseline model had slightly better precision than our approach, our Bi-LSTM model achieved much higher recall, resulting in the best F-measure. Our method can be generalized to extract medical concepts from social media for other medical applications.
Discovery of a keV-X-ray excess in RX J1856.5–3754
Authors: Yoneyama Tomokage , Hayashida Kiyoshi , Nakajima Hiroshi , Inoue Shota , Tsunemi Hiroshi
Published: April 2017

RX J1856.5−3754 is the brightest and nearest (∼120 pc) source among thermally emitting isolated neutron stars. Its spectra observed with XMM-Newton and Chandra satellites are well-fitted with the two-temperature (kT∞ ∼ 32 and 63 eV) blackbody model. Fitting ten sets of the data from Suzaku XIS 0, XIS 1, XIS 3, and XMM-Newton EPIC-pn with the two-temperature blackbody model, we discover an excess emission, 16%–26% in 0.8–1.2 keV. We examine possible causes of this keV-X-ray excess; uncertainty in the background, pile-up of the low-energy photons, and confusion of other sources. None of them succeeds in explaining the keV-X-ray excess observed with different instruments. We thus consider that this keV-X-ray excess most likely originates in RX J1856.5−3754. However, it is difficult to constrain the spectral shape of the keV-X-ray excess. A third blackbody component with $kT^\infty = 137^{+18}_{-14}\:$eV, an additional power-law component with a photon index $\Gamma = 3.4^{+0.5}_{-0.6}$, or Comptonization of blackbody seed photons into a power law with a photon index $\Gamma _{\rm c} = 4.3^{+0.8}_{-0.8}$ can reproduce the keV-X-ray excess. We also search for the periodicity of 0.8–1.2 keV data, since 7.055 s pulsation is discovered in the 0.15–1.2 keV band in the XMM Newton EPIC-pn data (∼1.5%). We only obtain the upper limit of pulsed fraction <3% in the keV-X-ray excess. We briefly discuss the possible origin of the keV-X-ray excess, such as synchrotron radiation and Comptonization of blackbody photons.
Serotonin Regulates the Feeding and Reproductive Behaviors of Pratylenchus penetrans
Authors: Han Ziduan , Boas Stephanie , Schroeder Nathan E.
Published: April 2017

The success of all plant-parasitic nematodes is dependent on the completion of several complex behaviors. The lesion nematode Pratylenchus penetrans is an economically important parasite of a diverse range of plant hosts. Unlike the cyst and root-knot nematodes, P. penetrans moves both within and outside of the host roots and can feed from both locations. Adult females of P. penetrans require insemination by actively moving males for reproduction and can lay eggs both within and outside of the host roots. We do not have a complete understanding of the molecular basis for these behaviors. One candidate modulator of these behaviors is the neurotransmitter serotonin. Previous research demonstrated an effect of exogenously applied serotonin on the feeding and male mating behaviors of cyst and root-knot nematodes. However, there are no data on the role of exogenous serotonin on lesion nematodes. Similarly, there are no data on the presence and function of endogenous serotonin in any plant-parasitic nematode. Here, we establish that exogenous serotonin applied to P. penetrans regulates both feeding and sex-specific behaviors. Furthermore, using immunohistochemistry and pharmacological assays, our data suggest that P. penetrans utilizes endogenous serotonin to regulate both feeding and sex-specific behaviors.
Nonhealing Ulcers in Patients with Tophaceous Gout: A Systematic Review
Authors: Lam Gretl , Ross Frank L. , Chiu Ernest S.
Published: April 2017

GENERAL PURPOSE:

To provide information from a review of the literature about chronic ulcers associated with tophaceous gout.

TARGET AUDIENCE:

This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care.

LEARNING OBJECTIVES/OUTCOMES:

After participating in this educational activity, the participant should be better able to:

1. Identify the pathophysiology of tophaceous gout, its presentation, phases, and common comorbidities.

2. Evaluate the findings in this review regarding effectiveness of interventions for chronic tophaceous ulcers.

OBJECTIVE:Treating chronic ulcers associated with tophaceous gout is an uncommon but important clinical challenge. However, treatments vary greatly from topical therapies, to debridements, to free flap wound coverage. To the authors’ knowledge, this is the first study to assemble and compare these different approaches in order to guide effective treatment.

DATA SOURCES:An electronic search of MEDLINE (PubMed) was conducted. Search terms included (goutandulcer)not“peptic ulcer,” and (gout, chronic wound)or(gout, nonhealing wound).

STUDY SELECTION:Studies that discussed the presentation, characterization, or treatment of gout-associated wounds were included. The literature search yielded 9 case reports and case series; there were no randomized controlled studies or reviews.

DATA EXTRACTION:Patient and wound characteristics, treatment approaches, and outcomes were noted.

DATA SYNTHESIS:The 82% of 22 patients were male, aged 36 to 95 years. Three patients had not been previously diagnosed with gout, whereas others had received a diagnosis 2 to 35 years prior to presentation with an ulcer. Many patients had comorbidities including diabetes and peripheral vascular disease. Most of the 43 total ulcers occurred on the feet. Treatments included topical 3% citric acid in petroleum jelly, allogeneic culture dermal substitute, silver-containing dressing and heterologous lyophilized collagen, debridements, and free flap coverage.

CONCLUSIONS:Chronic tophaceous wounds are a worldwide problem. Although physicians report some successes with different treatments, controlled studies are needed to determine the most effective approach and to identify risk factors and preventive strategies.
High Mortality Among Patients With Opioid Use Disorder in a Large Healthcare System
Authors: Hser Yih-Ing , Mooney Larissa J. , Saxon Andrew J. , Miotto Karen , Bell Douglas S. , Zhu Yuhui , Liang Di , Huang David
Published: April 2017

Objectives:

Elevated mortality has been observed among individuals with opioid use disorder (OUD) treated in addiction specialty clinics or programs. Information about OUD patients in general healthcare settings is needed in light of the current effort to integrate addiction services into primary healthcare systems. This study examined mortality rates, causes of death, and associated risk factors among patients with OUD in a large general healthcare system.

Methods:

Mortality data were linked with electronic health records of 2576 OUD patients cared for in a large university health system from 2006 to 2014.

Results:

There were 465 deaths confirmed (18.1% of the study participants), corresponding to a crude mortality rate of 48.6 per 1000 person-years and standardized mortality ratio of 10.3 (95% confidence interval [CI] 9.4–11.3). Drug overdose and disorder (19.8%), cardiovascular diseases (17.4%), cancer (16.8%), and infectious diseases (13.5%, including 12% hepatitis C virus [HCV]) were the leading causes of death. HCV (hazard ratio [HR] 1.99, 95% CI 1.62–2.46) and alcohol use disorder (HR 1.27, 95% CI 1.05–1.55) were 2 clinically important indicators of overall mortality risk. Tobacco use disorder (adjusted HR [AHR] 2.58, 95% CI 1.60–4.17) was associated with increased risk of cardiovascular death, HCV infection (AHR 2.55, 95% CI 1.52–4.26) with cancer mortality risk, and HCV (AHR 1.92, 95% CI 1.03–3.60) and alcohol use disorder (AHR 5.44, 95% CI 2.95–10.05) with liver-related mortality risk.

Conclusions:

Patients with OUD in a general healthcare system demonstrated alarmingly high morbidity and mortality, which challenges healthcare systems to find innovative ways to identify and treat patients with substance use disorder.
Attentional Avoidance is Associated With Increased Pain Sensitivity in Patients With Chronic Posttraumatic Pain and Comorbid Posttraumatic Stress
Authors: Harvold Mathea , MacLeod Colin , Vaegter Henrik B.
Published: April 2017

Objectives:

Posttraumatic stress disorder (PTSD) is common in chronic posttraumatic pain. Theoretical models suggest that attentional biases (AB) contribute to the development and maintenance of chronic pain and PTSD; however, the influence of AB on clinical and heat pain sensitivity in chronic posttraumatic pain patients is unknown. This study investigated AB for linguistic pain-related stimuli and trauma-related stimuli, and clinical and thermal sensitivity in patients with chronic posttraumatic pain with and without PTSD.

Materials and Methods:

In total, 34 patients with chronic posttraumatic cervical pain performed the visual attentional probe task assessing patterns of selective attentional responding to trauma cues and to pain cues. The task used short (500 ms) and long (1250 ms) stimulus exposure durations to ensure sensitivity to both the orienting and maintenance of attention. Heat pain threshold was assessed at the nonpainful hand. Clinical pain intensity, psychological distress (anxiety, depression, and disability), and PTSD symptomatology were assessed with questionnaires.

Results:

The Pain/PTSD group (N=14) demonstrated increased clinical and heat pain sensitivity as well as psychological distress compared with the Pain/No-PTSD group (N=20; P<0.05). AB scores were significantly different between groups (P=0.04). Irrespective of stimulus exposure duration, the Pain/PTSD group demonstrated attentional bias away from trauma and pain cues (avoidance), whereas the Pain/No-PTSD group demonstrated attentional bias toward pain cues (vigilance). Attentional avoidance of pain cues was associated with increased pain intensity and heat pain sensitivity (P<0.02).

Discussion:

These results suggest that attentional avoidance is associated with increased chronic posttraumatic pain. The causal contribution of attentional avoidance to pain outcomes remains unclear.
Triggering Receptor Expressed on Myeloid Cells 2, a Novel Regulator of Immunocyte Phenotypes, Confers Neuroprotection by Relieving Neuroinflammation
Authors: Zhai Qian , Li Feng , Chen Xiyao , Jia Ji , Sun Sisi , Zhou Dandan , Ma Lei , Jiang Tao , Bai Fuhai , Xiong Lize , Wang Qiang
Published: April 2017

Background

Microglia can not only detrimentally augment secondary injury but also potentially promote recovery. However, the mechanism underlying the regulation of microglial phenotypes after stroke remains unclear.

Methods

Mice were subjected to middle cerebral artery occlusion for 60 min. At 3 days after reperfusion, the effects of activation and suppression of triggering receptor expressed on myeloid cells 2 on immunocyte phenotypes (n = 5), neurobehavioral scores (n = 7), infarct volumes (n = 8), and neuronal apoptosis (n = 7) were analyzed. In vitro, cultured microglia were exposed to oxygen–glucose deprivation for 4 h. Inflammatory cytokines, cellular viability (n = 8), neuronal apoptosis (n = 7), and triggering receptor expressed on myeloid cells 2 expression (n = 5) were evaluated in the presence or absence of triggering receptor expressed on myeloid cell-specific small interfering RNA or triggering receptor expressed on myeloid cells 2 overexpression lentivirus.

Results

Triggering receptor expressed on myeloid cells 2 expression in the ischemic penumbra peaked at 3 days after ischemia–reperfusion injury (4.4 ± 0.1-fold, P = 0.0004) and was enhanced in interleukin-4/interleukin-13–treated microglia in vitro (1.7 ± 0.2-fold, P = 0.0119). After oxygen–glucose deprivation, triggering receptor expressed on myeloid cells 2 conferred neuroprotection by regulating the phenotypic conversion of microglia and inflammatory cytokine release. Intraperitoneal administration of triggering receptor expressed on myeloid cells 2 agonist heat shock protein 60 or unilateral delivery of a recombinant triggering receptor expressed on myeloid cells 2 lentivirus into the cerebral ventricle induced a significant neuroprotective effect in mice (apoptotic neurons decreased to 31.3 ± 7.6%; infarct volume decreased to 44.9 ± 5.3%). All values are presented as the mean ± SD.

Conclusions

Activation or up-regulation of triggering receptor expressed on myeloid cells 2 promoted the phenotypic conversion of microglia and decreased the number of apoptotic neurons. Our study suggests that triggering receptor expressed on myeloid cells 2 is a novel regulator of microglial phenotypes and may be a potential therapeutic target for stroke.
Hamstring Autograft Reconstruction of the Peroneus Brevis
Authors: Ellis Scott J. , Rosenbaum Andrew J.
Published: April 2017

Peroneal tendon tears are an underdiagnosed source of pain and disability in patients presenting with inversion type ankle injuries and lateral ankle and hindfoot pain. Operative treatment is indicated for symptomatic tears, as nonsurgical treatments are associated with poor clinical outcomes. There is no consensus regarding optimal surgical interventions, with primary repair, tenodesis of the peroneus longus to brevis, deep flexor tendon transfers (ie, flexor halluces longus), and allograft reconstruction all described. We present a novel technique utilizing hamstring autograft for the management of irreparable peroneus brevis tears.

Level of Evidence: Diagnostic Level V. See Instructions for Authors for a complete description of levels of evidence.
Short-course Regimens of Liposomal Amphotericin B for the Treatment of Mediterranean Visceral Leishmaniasis in Children
Authors: Krepis Panagiotis , Argyri Ioanna , Krepi Adamantia , Syrmou Areti , Spyridis Nikos , Tsolia Maria
Published: April 2017

Background:

Visceral leishmaniasis (VL) remains an important public health problem in endemic regions. Current antileishmanial agents share several limitations including potentially serious side effects and the risk of clinical failure.

Objectives:

Aim of this study was to examine the effectiveness and safety of short-course liposomal amphotericin B (L-AmB) regimens in the treatment of childhood VL in our area.

Methods:

The cases of 43 VL patients (20 males; 23 females; mean age: 4.6 years) treated at a tertiary children’s hospital over an 11-year period were retrospectively reviewed. Diagnosis was confirmed with identification of Leishmania spp. in bone marrow samples and/or a positive serologic test. All patients were treated with 5 different L-AmB regimens at a dose of 18–22 mg/kg.

Results:

Initial response to treatment was attained in all patients (100%), while definitive cure at 6 months was achieved in 98% of patients. Adverse effects were recorded in 14 children and consisted mostly of infusion reactions and electrolyte disorders. Self-limiting nephrotoxicity was observed in 3 patients including a 12-year-old girl in whom acute kidney injury was developed. In addition, ventricular arrhythmias developed in a 13-year-old boy necessitating drug discontinuation. Although side effects were more frequent with the 2-day regimen, the difference with regard to toxicity between dosing regimens was not significant.

Conclusions:

Short-course L-AmB regimens are effective and safe for the treatment of childhood VL in our area. Our findings suggest that large L-AmB doses can possibly account for a higher rate of adverse events including nephrotoxicity.
Altered neural responses to heat pain in drug-naive patients with Parkinson disease
Authors: Forkmann Katarina , Grashorn Wiebke , Schmidt Katharina , Fründt Odette , Buhmann Carsten , Bingel Ulrike
Published: April 2017

Pain is a frequent but still neglected nonmotor symptom of Parkinson disease (PD). However, neural mechanisms underlying pain in PD are poorly understood. Here, we explored whether the high prevalence of pain in PD might be related to dysfunctional descending pain control. Using functional magnetic resonance imaging we explored neural responses during the anticipation and processing of heat pain in 21 PD patients (Hoehn and Yahr I-III) and 23 healthy controls (HC). Parkinson disease patients were naive to dopaminergic medication to avoid confounding drug effects. Fifteen heat pain stimuli were applied to the participants' forearm. Intensity and unpleasantness ratings were provided for each stimulus. Subjective pain perception was comparable for PD patients and HC. Neural processing, however, differed between groups: PD patients showed lower activity in several descending pain modulation regions (dorsal anterior cingulate cortex [dACC], subgenual anterior cingulate cortex, and dorsolateral prefrontal cortex [DLPFC]) and lower functional connectivity between dACC and DLPFC during pain anticipation. Parkinson disease symptom severity was negatively correlated with dACC-DLPFC connectivity indicating impaired functional coupling of pain modulatory regions with disease progression. During pain perception PD patients showed higher midcingulate cortex activity compared with HC, which also scaled with PD severity. Interestingly, dACC-DLPFC connectivity during pain anticipation was negatively associated with midcingulate cortex activity during the receipt of pain in PD patients. This study indicates altered neural processing during the anticipation and receipt of experimental pain in drug-naive PD patients. It provides first evidence for a progressive decline in descending pain modulation in PD, which might be related to the high prevalence of pain in later stages of PD.
p16INK4a, Cytokeratin 7, and Ki-67 as Potential Markers for Low-Grade Cervical Intraepithelial Neoplasia Progression
Authors: da Costa Larissa Bastos Eloy , Triglia Renata De Marchi , Andrade Liliana A. Lucci De Angelo
Published: April 2017

Objective

The aim of this study was to evaluate p16INK4a, cytokeratin 7 (CK7), and Ki-67 immunoexpressions in low-grade squamous intraepithelial lesion (LSIL), looking for differences among cases that progress to high-grade squamous intraepithelial lesion, maintain LSIL, or regress.

Materials and Methods

Sixty-six LSIL biopsies were studied. In the follow-up, a second biopsy showed 28.7% regression, 37.9% LSIL, and 33.4% progressed to high-grade squamous intraepithelial lesion. Immunostaining for these markers were performed in the first biopsy. A qualitative evaluation method was used, as well as histomorphometry, using ImageJ software. Pearson χ2, Mann-Whitney, Kruskal-Wallis, and Fisher tests were used to compare the groups (P ≤ .05). A cutoff point was assessed through receiver operating characteristic curve positive cell ratio, for each marker, as progression predictors.

Results

The mean age of patients with and without progression was 33 and 27 years (P = .006), respectively. The qualitative evaluation indicated a tendency of progression, but without statistical significance. However, through histomorphometry, the receiver operating characteristic curve analysis showed cutoff points of 0.396, 0.345, and 0.026 for p16INK4a, CK7, and Ki-67 ratios, respectively, as predictors of progression (P = .003, .03, and .002, respectively). In a logistic regression analysis, p16INK4a, CK7, and Ki-67 positive cell ratio showed a significant correlation with progression (P = .036, .012, and .006, respectively).

Conclusions

p16INK4a, CK7, and Ki-67 may represent useful biomarkers that can identify LSIL lesions that need particular attention.
Family Functioning Predicts End-of-Life Care Quality in Patients With Cancer
Authors: Lee Myung Kyung , Yun Young Ho
Published: April 2017

Background:

Treating patients with cancer within a family setting is the accepted standard of care and a hallmark of end-of-life (EoL) quality of care (QoC).

Objective:

The aim of this study was to determine whether family caregiver functioning predicts EoL QoC received by terminally ill patients with cancer.

Methods:

Family caregivers of terminally ill patients with cancer (n = 264) were enrolled from oncology inpatient and outpatient units of 12 large hospitals located in different regions throughout South Korea. Caregivers were administered self-reported questionnaires about family functioning and EoL QoC at the time of an incurable cancer diagnosis, 4 to 6 weeks later, and again 2 to 3 months later. Family functioning and QoC were measured using the family Apgar and Quality Care Questionnaire–End of Life scales, respectively.

Results:

Improved adaptability to resource sharing and attention received predicted improved family relationships for the 3 time points. Increased participation in decision making and communication predicted improved individualized care and family relationships for the 3 time points. Increased affection predicted improvements in dignity-conserving care and family relationships for the 3 time points. Improved resolution regarding sharing time and satisfaction with commitments predicted increases in all QoC domains for the 3 time points, including dignity-conserving care, care by healthcare professionals, individualized care, and family relationships.

Conclusions:

Family functioning may contribute to improved EoL QoC of patients with terminal cancer.

Implications for Practice:

Patients' family caregivers are a valued source of affection and communicative support, improving EoL QoC. More family-oriented cancer support systems can better maintain the effectiveness of QoC until EoL.
Nursing Informatics Competency Assessment for the Nurse Leader
Authors: Yen Po-Yin , Phillips Andrew , Kennedy Mary K. , Collins Sarah
Published: April 2017

OBJECTIVE

The aim of this article is to refine and validate a new instrument, Nursing Informatics Competency Assessment for the Nurse Leader (NL).

BACKGROUND

Because health information technology rapidly advances, the NL requires greater levels of informatics knowledge.

METHODS

Item reduction and psychometric analysis methodology

RESULTS

A total of 357 national NLs completed the survey. Exploratory factor analysis resulted in a final 6-factor solution that contained 26 items: (1) strategic implementation management, (2) advanced information management and education, (3) executive planning, (4) ethical and legal concepts, (5) information systems concepts, and (6) requirements and system selection. Cronbach’s α were .96, .91, .90, .83, .92, .81, respectively.

CONCLUSION

We established a valid and reliable nursing informatics competency assessment instrument with sufficient specificity to guide NLs to recognize the competencies required in their role, create solutions to address potential gaps, and enhance delivery of patient care.
Endogenous Glucocorticoid Response to Single-Dose Dexamethasone for Croup in Children
Authors: Gill Natasha , Sirizzotti Natalie , Johnson David , Joubert Gary , Kucey Andrew S. , Tieu Alvin , Urquhart Brad L. , Columbus Melanie , Lim Rodrick , Rieder Michael , Mehrotra Shruti , Hartjes Emily D. , Poonai Naveen
Published: April 2017

Objectives

Dexamethasone is associated with adrenal insufficiency in adults and children with chronic disease. This association has not been studied after single-dose oral dexamethasone, the standard of care for children with croup. We hypothesized that single-dose oral dexamethasone in children with croup is associated with a transient decrease in endogenous glucocorticoids.

Methods

We conducted a prospective, 2-arm, pharmacodynamic study of single-dose oral dexamethasone 0.6 mg/kg (maximum, 12 mg) in children older than 2 years with croup compared with controls (children with febrile upper respiratory tract infections who did not receive dexamethasone). Primary outcome was urinary 6β-hydroxycortisol–cortisol ratio.

Results

Twenty-seven children were analyzed (22 with croup and 5 with upper respiratory tract infections). Median 6β-hydroxycortisol–cortisol ratios before dexamethasone, the following morning, and on days 1, 3, and 7 were 2.8, 2.2, 2.0, 2.8, and 2.6, respectively. Among controls, the median 6β-hydroxycortisol–cortisol ratios at the same time intervals was 1.9, 1.5, 1.8, 2.5, and 1.7, respectively. There were no significant differences in the change from time 0 between groups at any time point. There were no serious adverse events or infectious complications.

Conclusions

Single-dose oral dexamethasone is not associated with decreased endogenous corticosteroid levels in children with croup. Future studies should use criterion standard tests to rule out suppression of the hypothalamic-pituitary-adrenal axis and be powered sufficiently to identify adverse clinical outcomes.
Confronting Challenges in Monitoring and Evaluation: Innovation in the Context of the Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping Their Mothers Alive
Authors: Radin Anna K. , Abutu Andrew A. , Okwero Margaret A. , Adler Michelle R. , Anyaike Chukwuma , Asiimwe Hilda T. , Behumbiize Prosper , Efuntoye Timothy A. , King Rachel L. , Kisaakye Linda Nabitaka , Ogundehin Dolapo T. , Phelps Benjamin Ryan , Watts Heather , Weissglas Fitti
Published: April 2017

The Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping Their Mothers Alive (Global Plan), which was launched in 2011, set a series of ambitious targets, including a reduction of new HIV infections among children by 90% by 2015 (from a baseline year of 2009) and AIDS-related maternal mortality by 50% by 2015. To reach these targets, the Global Plan called for unprecedented investments in the prevention of mother-to-child transmission of HIV (PMTCT), innovative new approaches to service delivery, immense collective effort on the programmatic and policy fronts, and importantly, a renewed focus on data collection and use. We provide an overview of major achievements in monitoring and evaluation across Global Plan countries and highlight key challenges and innovative country-driven solutions using PMTCT program data. Specifically, we describe the following: (1) Uganda's development and use of a weekly reporting system for PMTCT using short message service technology that facilitates real-time monitoring and programmatic adjustments throughout the transition to a “treat all” approach for pregnant and breastfeeding women living with HIV (Option B+); (2) Uganda's work to eliminate parallel reporting systems while strengthening the national electronic district health information system; and (3) how routine PMTCT program data in Nigeria can be used to estimate HIV prevalence at the local level and address a critical gap in local descriptive epidemiologic data to better target limited resources. We also identify several ongoing challenges in data collection, analysis, and use, and we suggest potential solutions.
Lessons Learned From Option B+ in the Evolution Toward “Test and Start” From Malawi, Cameroon, and the United Republic of Tanzania
Authors: Kalua Thokozani , Tippett Barr Beth A. , van Oosterhout Joep J. , Mbori-Ngacha Dorothy , Schouten Erik J. , Gupta Sundeep , Sande Amakobe , Zomba Gerald , Tweya Hannock , Lungu Edgar , Kajoka Deborah , Tih Pius , Jahn Andreas
Published: April 2017

The acceleration of prevention of mother-to-child transmission (PMTCT) activities, coupled with the rollout of 2010 World Health Organization (WHO) guidelines, led to important discussions and innovations at global and country levels. One paradigm-shifting innovation was Option B+ in Malawi. It was later included in WHO guidelines and eventually adopted by all 22 Global Plan priority countries. This article presents Malawi's experience with designing and implementing Option B+ and provides complementary narratives from Cameroon and Tanzania. Malawi's HIV program started in 2002, but by 2009, the PMTCT program was lagging far behind the antiretroviral therapy (ART) program because of numerous health system challenges. When WHO recommended Option A and Option B for PMTCT in 2010, it was clear that Malawi's HIV program would not be able to successfully implement either option without increasing existing barriers to PMTCT services and potentially decreasing women's access to care. Subsequent stakeholder discussions led to the development of Option B+. Operationalizing Option B+ required several critical considerations, including the complete integration of ART and PMTCT programs, systematic reduction of barriers to facilitate doubling the number of ART sites in less than a year, building consensus with stakeholders, and securing additional resources for the new program. During the planning and implementation process, several lessons were learned which are considerations for countries transitioning to “treat-all”: Comprehensive change requires effective government leadership and coordination; national clinical guidelines must accommodate health system limitations; ART services and commodities should be decentralized within facilities; the general public should be well informed about major changes in the national HIV program; and patients should be educated on clinic processes to improve program monitoring.
Realizing the Promise of the Global Plan: Engaging Communities and Promoting the Health and Human Rights of Women Living With HIV
Authors: Matheson Rebecca , Brion Sophie , Sharma Aditi , Dilmitis Sophie , Schmitz Kathrin , Kean Stuart , Filous Katie , Murenga Maurine , Scheepers Esca , Ukoli Patricia , Mworeko Lillian , Yuvaraj Anandi
Published: April 2017

The Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping Their Mothers Alive highlighted the need to put the health and well-being of women and mothers at the center of efforts to prevent vertical transmission. This article will examine a selection of community engagement practices in 3 key areas: (1) as an accountability tool, (2) in service delivery, and (3) as a facilitator of human rights. The lived experiences of women living with HIV as recipients of and participants in services for the prevention of vertical transmission provide both the framework for an exploration of best community engagement practices and suggestions for the way forward.
Pediatric Treatment Scale-Up: The Unfinished Agenda of the Global Plan
Authors: Penazzato Martina , Amzel Anouk , Abrams Elaine J. , Kiragu Karusa , Essajee Shaffiq , Mukui Irene , Elyanu Peter , Rwebembera Anath A. , Mbori-Ngacha Dorothy
Published: April 2017

Five million children have died of AIDS-related causes since the beginning of the epidemic. In 2011, the Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping Their Mothers Alive (Global Plan) created the political environment to catalyze both the resources and commitment to end pediatric AIDS. Implementation and scale-up have encountered substantial hurdles, however, which have resulted in slow progress. Reasons include a lack of emphasis on testing outside of prevention of mother-to-child transmission services, an overall lack of integration and coordination with other services, a lack of training among providers, low confidence in caring for children living with HIV, and a lack of appropriate formulations for pediatric antiretrovirals. During the Global Plan period, we have learned that simplification is essential to successful decentralization, integration, and task shifting of services; that innovations require careful planning; and that the family is an important unit for delivering HIV care and treatment services. The post-Global Plan phase presents a number of noteworthy challenges that all stakeholders, national programs, and communities must tackle to guarantee universal treatment for children living with HIV. Accelerated action is essential in ensuring that HIV diagnosis and linkage to treatment happen as quickly and effectively as possible. As fewer infants are infected because of effective prevention of mother-to-child transmission interventions and the population of children living with HIV will age into adolescence adapting service delivery models to the epidemic context, and engaging the community will be critical to finding new efficiencies and allowing us to realize a true HIV-free generation—and to end AIDS by 2030.
Offering patients more: how the West Africa Ebola outbreak can shape innovation in therapeutic research for emerging and epidemic infections
Authors: Rojek Amanda M. , Horby Peter W.
Published: April 2017

Although, after an epidemic of over 28 000 cases, there are still no licensed treatments for Ebola virus disease (EVD), significant progress was made during the West Africa outbreak. The pace of pre-clinical development was exceptional and a number of therapeutic clinical trials were conducted in the face of considerable challenges. Given the on-going risk of emerging infectious disease outbreaks in an era of unprecedented population density, international travel and human impact on the environment it is pertinent to focus on improving the research and development landscape for treatments of emerging and epidemic-prone infections. This is especially the case since there are no licensed therapeutics for some of the diseases considered by the World Health Organization as most likely to cause severe outbreaks—including Middle East respiratory syndrome coronavirus, Marburg virus, Crimean Congo haemorrhagic fever and Nipah virus. EVD, therefore, provides a timely exemplar to discuss the barriers, enablers and incentives needed to find effective treatments in advance of health emergencies caused by emerging infectious diseases.

This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’.
Assessments of Ebola knowledge, attitudes and practices in Forécariah, Guinea and Kambia, Sierra Leone, July–August 2015
Authors: Jalloh Mohamed F. , Bunnell Rebecca , Robinson Susan , Jalloh Mohammad B. , Barry Alpha Mamoudou , Corker Jamaica , Sengeh Paul , VanSteelandt Amanda , Li Wenshu , Dafae Foday , Diallo Alpha Ahmadou , Martel Lise D. , Hersey Sara , Marston Barbara , Morgan Oliver , Redd John T.
Published: April 2017

The border region of Forécariah (Guinea) and Kambia (Sierra Leone) was of immense interest to the West Africa Ebola response. Cross-sectional household surveys with multi-stage cluster sampling procedure were used to collect random samples from Kambia (
n
= 635) in July 2015 and Forécariah (
n
= 502) in August 2015 to assess public knowledge, attitudes and practices related to Ebola. Knowledge of the disease was high in both places, and handwashing with soap and water was the most widespread prevention practice. Acceptance of safe alternatives to traditional burials was significantly lower in Forécariah compared with Kambia. In both locations, there was a minority who held discriminatory attitudes towards survivors. Radio was the predominant source of information in both locations, but those from Kambia were more likely to have received Ebola information from community sources (mosques/churches, community meetings or health workers) compared with those in Forécariah. These findings contextualize the utility of Ebola health messaging during the epidemic and suggest the importance of continued partnership with community leaders, including religious leaders, as a prominent part of future public health protection.

This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’.