bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards self-learning based hypotheses generation in biomedical text domain
Authors: Gopalakrishnan Vishrawas , Jha Kishlay , Xun Guangxu , Ngo Hung Q , Zhang Aidong
Published: December 2017

Motivation

The overwhelming amount of research articles in the domain of bio-medicine might cause important connections to remain unnoticed. Literature Based Discovery is a sub-field within biomedical text mining that peruses these articles to formulate high confident hypotheses on possible connections between medical concepts. Although many alternate methodologies have been proposed over the last decade, they still suffer from scalability issues. The primary reason, apart from the dense inter-connections between biological concepts, is the absence of information on the factors that lead to the edge-formation. In this work, we formulate this problem as a collaborative filtering task and leverage a relatively new concept of word-vectors to learn and mimic the implicit edge-formation process. Along with single-class classifier, we prune the search-space of redundant and irrelevant hypotheses to increase the efficiency of the system and at the same time maintaining and in some cases even boosting the overall accuracy.

Results

We show that our proposed framework is able to prune up to 90% of the hypotheses while still retaining high recall in top-K results. This level of efficiency enables the discovery algorithm to look for higher-order hypotheses, something that was infeasible until now. Furthermore, the generic formulation allows our approach to be agile to perform both open and closed discovery. We also experimentally validate that the core data-structures upon which the system bases its decision has a high concordance with the opinion of the experts.This coupled with the ability to understand the edge formation process provides us with interpretable results without any manual intervention.

Availability and implementation

The relevant JAVA codes are available at: https://github.com/vishrawas/Medline–Code_v2.

Supplementary information

Supplementary data are available at Bioinformatics online.
Predictors of Secondary Role Strains Among Spousal Caregivers of Older Adults With Functional Disability
Authors: Polenick Courtney A , DePasquale Nicole
Published: December 2017

Background and Objectives

Aging spouses commonly care for a partner with functional disability, but little is known about how spousal caregiving may impact different life domains. This study evaluated how caregiving characteristics are associated with secondary role strains among spousal caregivers.

Research Design and Methods

This cross-sectional study examined 367 spousal caregivers and their partners from the 2011 National Health and Aging Trends Study and National Study of Caregiving. Hierarchical regressions were estimated to determine how caregiver background factors (sociodemographics, health conditions) along with primary objective (care activities, care recipient health conditions, and dementia status) and subjective (emotional caregiving difficulties, role overload) stressors are linked to care-related valued activity restriction, negative caregiving relationship quality, and care-related family disagreements. Gender differences were considered.

Results

After accounting for all predictors, older caregivers and caregivers providing more help with activities of daily living and health system interactions (e.g., scheduling appointments) were more likely to report activity restriction, whereas caregivers with more emotional difficulties reported higher negative caregiving relationship quality. Role overload was positively associated with all three secondary strains. For husbands only, caring for a partner with more chronic conditions was linked to higher negative caregiving relationship quality and caring for a partner with dementia was associated with a greater likelihood of family disagreements.

Discussion and Implications

Secondary role strains may develop through similar and unique pathways for caregiving wives and husbands. Further research is needed to identify those who could benefit from support in managing their care responsibilities alongside other life areas.
Clinical Updates in Women’s Health Care Summary: Common Dermatologic Conditions
Authors: Khorsand Kate O. , Iyer Jayasri G. , Abson Kim Gittere
Published: December 2017

The skin is the largest organ in the human body, and as such, cutaneous problems constitute a common component of visits to medical professionals. The skin functions as a physiologic barrier and a major organ of homeostasis. The practicing obstetrician–gynecologist can play an important role in identifying skin diseases and initiating management. Additionally, the skin often reflects internal disease states. An astute health care provider can identify systemic conditions early, with the goal of improving management. This monograph reviews common cutaneous conditions, both benign and malignant, hair and nail disorders, and skin conditions unique to the adult woman.
Isolated Traumatic Subarachnoid Hemorrhage: An Evaluation of Critical Care Unit Admission Practices and Outcomes From a North American Perspective
Authors: Witiw Christopher D. , Byrne James P. , Nassiri Farshad , Badhiwala Jetan H. , Nathens Avery B. , da Costa Leodante B.
Published: December 2017

Objectives:

Traumatic subarachnoid hemorrhage is a common radiographic finding associated with traumatic brain injury. The objective of this investigation is to evaluate the association between hospital-level ICU admission practices and clinically important outcomes for patients with isolated traumatic subarachnoid hemorrhage and mild clinical traumatic brain injury.

Design:

Multicenter observational cohort.

Setting:

Trauma centers participating in the American College of Surgeons Trauma Quality Improvement Program spanning January 2012 to March 2014.

Patients:

A total of 14,146 subjects, 16 years old and older, admitted to 215 trauma centers with isolated traumatic subarachnoid hemorrhage and Glasgow Coma Scale score 13 or greater. Patients with concurrent intracranial injuries, severe injury to other body regions, or tests positive for alcohol or illicit substances were excluded.

Intervention:

ICU admission.

Measurements and Main Results:

The primary outcome was need for neurosurgical intervention, defined as insertion of an intracranial monitor/drain or craniectomy/craniotomy. Secondary outcomes describing the clinical course included hospital discharge disposition, in-hospital mortality, and length of stay. Admission to ICU was common within the cohort (44.6%), yet the need for neurosurgical intervention was rare (0.24%). Variability was high between centers and remained so after adjusting for differences in case-mix and hospital-level characteristics (median odds ratio, 4.1). No significant differences in neurosurgical interventions, mortality, or discharge disposition to home under self-care were observed between groups of the highest and lowest ICU admitting hospitals. However, those in highest admitting group “stayed” in hospital 1.13 (95% CI, 1.07–1.20; p < 0.001) times that of the lowest admitting group.

Conclusions:

Critical care admission for mild traumatic brain injury patients with isolated traumatic subarachnoid hemorrhage is frequent and highly variable despite low probability of requiring neurosurgical intervention. Reevaluation of hospital-level practices may represent an opportunity for resource optimization when managing patients with mild clinical traumatic brain injury and associated isolated traumatic subarachnoid hemorrhage.
Effect of Rehabilitation on Sleep Quality After Ablation for Atrial Fibrillation
Authors: Risom Signe Stelling , Fevejle Cromhout Pernille , Overgaard Dorthe , Hastrup Svendsen Jesper , Kikkenborg Berg Selina
Published: December 2017

Background:

Low sleep quality is common in patients with atrial fibrillation (AF). Positive effects of cardiac rehabilitation on patients treated for AF with ablation have been found, but whether cardiac rehabilitation affects sleep quality is unknown. The objectives of this study were to investigate (1) differences in sleep quality between cardiac rehabilitation and usual care groups and (2) whether other factors could affect sleep quality.

Methods:

From the randomized CopenHeartRFA trial, 210 patients treated for AF with ablation were included. A rehabilitation program consisting of physical exercise and psychoeducational consultations was tested. Sleep quality was measured with the Pittsburg Sleep Quality Index (PSQI) questionnaire before intervention and at the end of intervention. Anxiety, depression, and European Heart Rhythm Association scores were assessed.

Results:

No difference between groups in sleep quality was found (PSQI global mean [SD] score, 6.60 [3.61] points for the cardiac rehabilitation group [n = 83] and 6.08 [3.60] points for the usual care group [n = 90]; P = .34), although improvements in sleep quality were noted in both groups. Sleep latency, duration, and efficiency were significant by type of AF at 1 month. Anxiety, depression, and higher European Heart Rhythm Association scores at 4 months were associated with a higher PSQI global mean score at the end of intervention.

Conclusion:

The rehabilitation program showed no effect on sleep quality. A large proportion of patients reported poor sleep quality, and patients reporting anxiety, depression, or AF symptoms described worse sleep quality compared with patients who did not experience anxiety, depression, or AF symptoms. More research in the field is warranted.
Open Wounds and Healed Scars
Authors: van Ee Birgit , Smits Carolien , Honkoop Aafke , Kamper Ad , Slaets Joris , Hagedoorn Mariët
Published: December 2017

Background

Breast cancer is more prevalent among women 60 years or older than among women younger than 60 years. However, we know much more about the breast cancer experiences of younger women than of older women. Such knowledge is important, for example, to guide treatment decisions or to provide psychosocial care.

Objective

The aim of this study was to gain insight into the experiences of women with breast cancer 70 years or older.

Methods

Semistructured interviews were conducted with 21 older patients with breast cancer in the Netherlands. We used open coding and affinity diagramming to evoke the themes reflecting the experiences of these women.

Results

Four themes emerged from the data: living through and coping with breast cancer, information exchange and informed choice, support experiences, and impact on daily life. Getting breast cancer took some women by surprise. However, older women with breast cancer coped fairly well and were satisfied with the support they received, especially from oncology nurses. Disturbing treatment adverse effects and changes in appearance, comorbid diseases, lack of clear information, and/or an unsupportive environment complicated their living with breast cancer.

Conclusions

Even though many older women with breast cancer handle their disease rather well, some women do encounter difficulties. Lack of support, comorbid diseases, and treatment adverse effects warrant extra attention.

Implications for Practice

Nurses’ close attention to women at risk and early intervention could help relieve individual suffering, while taking these womens’ strengths into account can enhance self-management.
Students’ Midprogram Content Area Performance as a Predictor of End-of-Program NCLEX Readiness
Authors: Brussow Jennifer A. , Dunham Michelle
Published: December 2017

Many programs have implemented end-of-program predictive testing to identify students at risk of NCLEX-RN failure. Unfortunately, for many students, end-of-program testing comes too late. Regression and relative importance analysis were used to explore relationships between 9 content area assessments and an end-of-program assessment shown to be predictive of NCLEX-RN success. Results indicate that scores on assessments for content areas such as medical surgical nursing and care of children are predictive of end-of-program test scores, suggesting that instructors should provide remediation at the first sign of lagging performance.
Major Barbara Stimson
Authors: Haisley Kelly R. , Drexel Sabrina E. , Watters Jennifer M. , Hunter John G. , Mullins Richard J.
Published: December 2017

Dr. Barbara Bartlett Stimson, AB, MD, MedScD, FACS (1898–1986) was a pioneering orthopedic surgeon from a prominent American family who, in 1940, became the first woman certified by the American Board of Surgery (ABS, certificate number 860). It would be another 7 years and approximately 2500 candidates before the next female surgeon would be certified. A member of the third class to admit women to Columbia Medical School and the second female surgical resident to complete training at Columbia-Presbyterian Medical Center, Dr. Stimson was a confident and exceptionally accomplished trailblazer for women in surgery. In this biographical sketch based upon documents from the ABS, and the archives of Vassar College and the College of Physicians and Surgeons at Columbia-Presbyterian Medical Center, Dr. Stimson's motivations, attitudes, and unique accomplishments emerge as testimony to the exceptional career of this driven, self-possessed woman. Stimson was undaunted by the sex-based conventions of her time, and achieved a notable career as a surgeon in the profession she loved; first honing her skills at a busy urban fracture service in New York, then serving with distinction in the Royal Army Medical Corps during World War II, and finally returning to the states to become a respected leader in her field. Her life story and unprecedented ABS certification affirm her conviction that proven skill and ability can be used as a means of overcoming unfounded biases, and helped pave the way for future generations of board certified female surgeons in the United States.
Screening for distress in survivorship
Authors: Girgis Afaf , Smith Allan B. , Durcinoska Ivana
Published: December 2017

Purpose of review

The current review provides an overview of recent research and other initiatives aimed at increasing and/or systematizing screening for distress in cancer survivors. It is timely given an increasing drive internationally to implement distress screening as part of routine cancer care.

Recent findings

Screening using brief validated tools is recommended and the single-item distress thermometer continues to be the international screening tool of choice. Although debate continues regarding the most appropriate cut-off distress thermometer score to identify clinically distressed patients, review of checked items from the accompanying problem list can pinpoint sources of distress, to inform targeted intervention. An integrated approach should include screening, and if required, assessment/referral and intervention. However, whilst distress screening is associated with some impact on referral, especially its timeliness, delivery of evidence-based treatments to address identified distress may be limited by patients declining help and a lack of support services.

Although screening for distress in routine care holds promise for reducing costs and enhancing health system efficiency, its implementation across cancer services is variable. Further research is required to evaluate screening implementation and sustainability in routine care, as well as the feasibility of distress screening in long-term cancer survivors who are no longer in regular contact with cancer centres.
Intelligent use of antiepileptic drugs is beneficial to patients
Authors: Cheng Jocelyn Y. , French Jacqueline A.
Published: December 2017

Purpose of review

To describe the most important issues a clinician must consider whenever selecting and administering antiepileptic drugs (AEDs). There is no available algorithm that identifies how to individualize selection of AEDs. Proper selection and administration can make an enormous difference in both effectiveness and tolerability.

Recent findings

Many principles of AED selection remain unchanged. Selection of AEDs must be based on understanding of epilepsy syndrome and seizure type, comorbidities, risk of adverse events, as well as on patient characteristics such as age and sex. Recently personalized medicine through genetics has become a reality for a subset of patients, to select optimal drugs, and avoid side effects. Selection of AEDs for women can be performed to avoid teratogenic agents, as safer AEDs have been identified. There is evidence supporting use of controlled release AED formulations, whenever available. Whenever selecting an optimal dose, physicians should attend to the principle of ‘start low, go slow.’ ‘Intelligent use’ includes not only appropriate drug selection, but also optimal and individualized dose adjustment. Drug optimization involves appropriate titration, dose schedule, individualization of therapeutic range and rescue planning

Intelligent drug use, individualized to patient characteristics, can guide management for optimal seizure control.
Correcting values of DNA sequence similarity for errors in sequencing
Authors: Hackmann Timothy J.
Published: December 2017

The similarity between two DNA sequences is one of the most important measures in bioinformatics, but errors introduced during sequencing make values of similarity lower than they should be. Here we develop a method to correct raw sequence similarity for sequencing errors and estimate the original sequence similarity. Our method is simple and consists of a single equation with terms for 1) raw sequence similarity and 2) error rates (e.g., from Phred quality scores). We show the importance of this correction for 16S ribosomal DNA sequences from bacterial communities, where 97% similarity is a frequent threshold for clustering sequences for analysis. At that threshold and typical error rate of 0.2%, correcting for error increases similarity by 0.36 percentage points. This result shows that, if uncorrected, sequencing error would increase similarity thresholds and generate false clusters for analysis. Our method could be used to adjust thresholds for cluster-based analyses. Alternatively, because it requires no clustering to correct sequence similarity, it could usher in a new age of analyzing ribosomal DNA sequences without clustering.
Impaired expected value computations coupled with overreliance on prediction error learning in schizophrenia
Authors: Hernaus D , Gold JM , Waltz JA , Frank MJ
Published: December 2017

Background

While many have emphasized impaired reward prediction error (RPE) signaling in schizophrenia, multiple studies suggest that some decision-making deficits may arise from overreliance on RPE systems together with a compromised ability to represent expected value. Guided by computational frameworks, we formulated and tested two scenarios in which maladaptive representation of expected value should be most evident, thereby delineating conditions that may evoke decision-making impairments in schizophrenia.

Methods

In a modified reinforcement learning paradigm, 42 medicated people with schizophrenia (PSZ) and 36 healthy volunteers learned to select the most frequently rewarded option in a 75-25 pair: once when presented with more deterministic (90–10) and once when presented with more probabilistic (60–40) pairs. Novel and old combinations of choice options were presented in a subsequent transfer phase. Computational modeling was employed to elucidate contributions from RPE systems (“actor-critic”) and expected value (“Q-leaming”).

Results

PSZ showed robust performance impairments with increasing value difference between two competing options, which strongly correlated with decreased contributions from expected value-based (“Q-leaming”) learning. Moreover, a subtle yet consistent contextual choice bias for the “probabilistic” 75 option was present in PSZ, which could be accounted for by a context-dependent RPE in the “actor-critic”.

Conclusions

We provide evidence that decision-making impairments in schizophrenia increase monotonically with demands placed on expected value computations. A contextual choice bias is consistent with overreliance on RPE-based learning, which may signify a deficit secondary to the maladaptive representation of expected value. These results shed new light on conditions under which decisionmaking impairments may arise.
A jump distance based parameter inference scheme for particulate trajectories in biological settings
Authors: Menssen Rebecca , Mani Madhav
Published: December 2017

One type of biological data that needs more quantitative analytical tools is particulate trajectories. This type of data appears in many different contexts and across scales in biology: from the trajectory of bacteria performing chemotaxis to the mobility of ms2 spots within nuclei. Presently, most analyses performed on data of this nature has been limited to mean square displacement (MSD) analyses. While simple, MSD analysis has several pitfalls, including difficulty in selecting between competing models, handling systems with multiple distinct sub-populations, and parameter extraction from limited time-series data. Here, we provide an alternative to MSD analysis using the jump distance distribution (JDD). The JDD resolves several issues: one can select between competing models of motion, have composite models that allow for multiple populations, and have improved error bounds on parameter estimates when data is limited. A major consequence is that you can perform analyses using a fraction of the data required to get similar results using MSD analyses, thereby giving access to a larger range of temporal dynamics when the underlying stochastic process is not stationary. In this paper, we construct and validate a derivation of the JDD for different transport models, explore the dependence on dimensionality of the process, and implement a parameter estimation and model selection scheme. We demonstrate the power of this scheme through an analysis of bacterial chemotaxis data, highlighting the interpretation of results and improvements upon MSD analysis. We expect that our proposed scheme provides quantitative insights into a broad spectrum of biological phenomena requiring analysis of particulate trajectories.
Rap2 and TNIK control Plexin-dependent synaptic tiling in C. elegans
Authors: Chen Xi , Shibata Akihiro C.E. , Hendi Ardalan , Kurashina Mizuki , Fortes Ethan , Weilinger Nicholas L , MacVicar Brian , Murakoshi Hideji , Mizumoto Kota
Published: December 2017

During development, neurons form synapses with their fate-determined targets. While we begin to elucidate the mechanisms by which extracellular ligand-receptor interactions enhance synapse specificity by inhibiting synaptogenesis, our knowledge about their intracellular mechanisms remains limited. Here we show that Rap2 GTPase (rap-2) and its effector, TNIK (mig-15), act downstream of Plexin (plx-1) to restrict presynaptic assembly and to form tiled synaptic innervation in C. elegans. Both constitutively GTP- and GDP-forms of rap-2 mutants exhibit synaptic tiling defects as plx-1 mutants, suggesting that cycling of the RAP-2 nucleotide state is critical for synapse inhibition. Consistently, RAP-2 activity is locally suppressed by PLX-1. Excessive ectopic synapse formation in mig-15 mutants causes a severe synaptic tiling defect. Conversely, overexpression of mig-15 strongly inhibited synapse formation, suggesting that mig-15 is a negative regulator of synapse formation. These results reveal that subcellular regulation of small GTPase activity by Plexin shapes proper synapse patterning in vivo.
The genomic false shuffle: epigenetic maintenance of topological domains in the rearranged gibbon genome
Authors: Lazar Nathan H. , Nevonen Kimberly A. , O’Connell Brendan , Green Richard E. , Meyer Thomas J. , Okhovat Mariam , Carbone Lucia
Published: December 2017

The relationship between evolutionary genome remodeling and the three-dimensional structure of the genome remain largely unexplored. Here we use the heavily rearranged gibbon genome to examine how evolutionary chromosomal rearrangements impact genome-wide chromatin interactions, topologically associating domains (TADs), and their epigenetic landscape. We use high-resolution maps of gibbon-human breaks of synteny (BOS), apply Hi-C in gibbon, measure an array of epigenetic features, and perform cross-species comparisons. We find that gibbon rearrangements occur at TAD boundaries, independent of the parameters used to identify TADs. This overlap is supported by a remarkable genetic and epigenetic similarity between BOS and TAD boundaries, namely presence of CpG islands and SINE elements, and enrichment in CTCF and H3K4me3 binding. Cross-species comparisons reveal that regions orthologous to BOS also correspond with boundaries of large (400-600kb) TADs in human and other mammalian species. The co-localization of rearrangement breakpoints and TAD boundaries may be due to higher chromatin fragility at these locations and/or increased selective pressure against rearrangements that disrupt TAD integrity. We also examine the small portion of BOS that did not overlap with TAD boundaries and gave rise to novel TADs in the gibbon genome. We postulate that these new TADs generally lack deleterious consequences. Lastly, we show that limited epigenetic homogenization occurs across breakpoints, irrespective of their time of occurrence in the gibbon lineage. Overall, our findings demonstrate remarkable conservation of chromatin interactions and epigenetic landscape in gibbons, in spite of extensive genomic shuffling.
Dynamics of HCV epidemiology in Aydin province of Turkey and the associated factors
Authors: Kirdar Sevin , Aydin Neriman , Tiryaki Yasin , Ertugrul Bulent , Coskun Adil , Bilgen Mehmet
Published: December 2017

This paper gives an update on the local distributions of HCV genotypes in Aydin province of Turkey, provides a comparison with the previous records, and discusses the potential causal reasons shaping the evolving genotype profiles. Patient files from 2011 to 2016 were retrospectively analyzed, and newly detected cases were documented. Out of 286 patients, male and female ratios were determined to remain nearly the same (~50%). Genotype 1 was still the most common (90.2%), followed by genotype 3 (5.9%), genotype 2 (2.1%), and genotype 4 (1.4%) in frequency. There were international patients (4.50%). One patient had genotyped 2+3 together. Genotypes 4 and 2+3 were detected for the first time, and the patients with genotype 4 were interestingly all male and also domestic individuals. However, these patients traveled or lived abroad in the past due to occupational reasons, thereby likely acquired the infection while abroad. HCV surveillance system is currently inadequate and some infected patients may go undetected in the province. Remapping the regional distribution of HCV genotypes from time‐to‐time is required for identifying the local dynamics and causes leading to it. This process enhances the clinical preparation and readiness for the better management of the disease.
Increased proportions of B cells with spontaneous production of interleukin‐10 in HIV‐infected individuals are normalized during combination antiretroviral therapy: a longitudinal study
Authors: Sambleben Camilla , Knudsen Andreas Dehlbæk , Hartling Hans J. , Nielsen Claus H. , Nielsen Susanne D.
Published: December 2017

Interleukin‐10 (IL‐10)‐producing B cells (B10 cells) may inhibit HIV‐specific T cells and are elevated in untreated HIV infection. We aimed to determine the effect of combination antiretroviral treatment (cART) on the proportion of B10 cells. Furthermore, we compared B10‐cell proportions in HIV‐infected progressors and viremic controllers. This was a prospective study including HIV‐infected progressors, viremic controllers and healthy controls. Progressors initiating cART were followed for 6 months. Purified B cells were stimulated with CpG, alone or in combination with HIV gp120, and the proportion of B10 cells was measured by flow cytometry. Without stimulation, the B10‐cell proportion was higher in progressors than in healthy controls, while viremic controllers and healthy controls had comparable proportions. Moreover, the proportion of CD24hiCD38hi transitional B cells was higher in progressors than in healthy controls. After initiation of cART, the proportion of B10 cells and transitional B cells decreased. In conclusion, progressors had elevated B10‐cell proportions, while viremic controllers displayed normal proportions. After initiation of cART, the B10‐cell proportion decreased. This could limit B10‐cell‐mediated suppression of specific CD8+ T‐cell responses.
Is “early intervention” in bipolar disorder what it claims to be?
Authors: Malhi Gin S , Morris Grace , Hamilton Amber , Outhred Tim , Mannie Zola
Published: December 2017

Background

The notion of early intervention is understandably appealing for conditions such as bipolar disorder (BD), a chronic life‐long illness that increases risk of suicide and diminishes quality of life. It is purported that intervening early in the course of the illness with suitable interventions could substantially alter the trajectory of BD and improve outcomes. However, while there are obvious benefits to the prompt commencement of treatment, it is important to consider the gaps in our understanding regarding the aetiopathogenesis of bipolar disorder—upon which the paradigm of early intervention is predicated.

Methods

A literature search was undertaken using recognized search engines: PubMed, PsycINFO Medline, and Scopus, along with auxiliary manual searches.

Results

This review first examines how the unpredictable nature of BD creates substantial difficulties when determining an optimal therapeutic target for early intervention. Second, the challenges with identifying appropriate populations and apposite times for early intervention strategies is discussed. Finally, the risks associated with intervening early are examined, highlighting the potential harmful effects of initiating medication.

Conclusion

Early intervention for BD is a potentially useful strategy that warrants investigation, but until the emergence and trajectory of the illness are definitive, and a clear view of key targets is achieved, a more conservative approach to treating nascent BD and its antecedent symptoms is needed.
How I manage patients with inherited haemophilia A and B and factor inhibitors
Authors: Ljung Rolf C. R.
Published: December 2017

Development of inhibitors to coagulation factor VIII or IX is still the most challenging complication in haemophilia care. ‘Bypassing agents’ may be used to treat a bleed but the eradication of the inhibitor by immune tolerance induction (ITI) is the main objective in the treatment of a patient with haemophilia who has developed neutralizing antibodies. Several options exist for ITI and the patient may be at ‘good’ or ‘bad risk’ for successful outcome with different regimens. This paper offers a review of current regimens to be considered in the treatment of a bleed in a patient with an inhibitor but the main focus is the aspects of different choices in the management of the child or the adult with severe or mild forms of haemophilia A or B, who has developed an inhibitor. There are also some final outlooks on new and emerging treatment possibilities.
Pre‐treatment neutrophil/lymphocyte ratio and platelet/lymphocyte ratio are prognostic of progression in early stage classical Hodgkin lymphoma
Authors: Reddy Jay P. , Hernandez Mike , Gunther Jillian R. , Dabaja Bouthaina S. , Martin Geoffrey V. , Jiang Wen , Akhtari Mani , Allen Pamela K. , Atkinson Bradley J. , Smith Grace L. , Pinnix Chelsea C. , Milgrom Sarah A. , Abou Yehia Zeinab , Osborne Eleanor M. , Oki Yasuhiro , Lee Hun , Hagemeister Fredrick , Fanale Michelle A.
Published: December 2017

To determine whether pre‐treatment neutrophil/lymphocyte (NLR) or platelet/lymphocyte ratios (PLR) are predictive for progression in early‐stage classical Hodgkin lymphoma (cHL), we derived NLR and PLR values for 338 stage I/II cHL patients and appropriate cut‐off point values to define progression. Two‐year freedom from progression (FFP) for patients with NLR ≥6·4 was 82·2% vs. 95·7% with NLR <6·4 (P < 0·001). Similarly, 2‐year FFP was 84·3% for patients with PLR ≥266·2 vs. 96·1% with PLR <266·2 (P = 0·003). On univariate analysis, both NLR and PLR were significantly associated with worse FFP (P = 0·001). On multivariate analysis, PLR remained a significant, independent prognostic factor (P < 0·001).
FINANCIAL CRISES, OUTPUT LOSSES, AND THE ROLE OF STRUCTURAL REFORMS
Authors: Tola Albi , Waelti Sébastien
Published: December 2017

Financial crises take a heavy toll on output growth. We assess the role of structural reforms in reducing the output losses resulting from financial crises across advanced economies, emerging and developing economies, and low‐income developing economies. We also revisit the role of macroeconomic policies in this context. The impact of crises on output growth differs between types of crises and economies, thus warranting sample splits along these lines. Some but not all reforms and policies help to reduce the output losses of crises in the medium term, highlighting the need not to overgeneralize the effectiveness of reforms and policies. Further research is warranted to further explore the heterogeneity in the impact of financial crises on output growth and to better understand when and how specific structural reforms and macroeconomic policies can mitigate the output costs of financial crises. (JEL E32, E44, E63, G28, O47)
Effects of organic matter coatings on the mobility of goethite colloids in model sand and undisturbed soil
Authors: Carstens J. F. , Bachmann J. , Neuweiler I.
Published: December 2017

The mobility of goethite (OMCG) colloids coated with organic matter was studied in goethite‐coated quartz sand and in undisturbed subsoil rich in natural coatings of iron oxide. Classic Derjaguin–Landau–Verwey–Overbeek (DLVO) interactions and DLVO extended by Lewis acid–base parameters (XDLVO) were estimated between colloids and goethite‐coated sand from zeta potentials and sessile drop contact angles. The OMCG colloids were retained completely in goethite‐coated sand, whereas preconditioning of the solid matrix with dissolved organic matter (DOM) enabled subsequent colloid transport. Zeta potential values showed that goethite‐coated sand was modified strongly by DOM preconditioning. The DLVO and XDLVO interactions were estimated for the pairs of OMCG colloids and for (i) quartz, (ii) goethite and (iii) organic matter‐coated goethite. Both DLVO approaches were able to predict general trends of colloid breakthrough. An exception was the XDLVO interaction for combination (iii), which showed short‐distance (<1.3 nm) repulsive interactions that were inconsistent with breakthrough behaviour. Analogous to OMCG colloid transport in the sand, DOM preconditioning was also the prerequisite for OMCG colloid transport in undisturbed subsoil. Total colloid breakthrough in the soil was less than in the sand, probably because of straining in pore throats and retention at air–water interfaces. We concluded that the DLVO and XDLVO approaches were in general capable of predicting trends of OMCG colloid mobility in goethite‐coated sand. We concluded further that the basic principles of OMCG colloid transport were transferrable from the simplified model system to the more complex natural system despite considerable differences in surface properties, pore structure and water content.

Highlights

How will organic matter (OM) coatings on the solid matrix affect mobility of iron oxide colloids?

Effect of OM on mobility was assessed in simple model soil systems and in undisturbed soil.

OM coatings modify properties of the solid matrix surface and are a prerequisite for colloid transport.

Balances between OM transport, coating formation and decomposition control colloid mobility.
Disruption of circadian clockwork in in vivo reprogramming‐induced mouse kidney tumors
Authors: Ohashi Munehiro , Umemura Yasuhiro , Koike Nobuya , Tsuchiya Yoshiki , Inada Yutaka , Watanabe Hitomi , Tanaka Tomoko , Minami Yoichi , Ukimura Osamu , Miki Tsuneharu , Tajiri Tatsuro , Kondoh Gen , Yamada Yasuhiro , Yagita Kazuhiro
Published: December 2017

The circadian clock, which regulates cellular physiology, such as energy metabolism, resides in each cell level throughout the body. Recently, it has been elucidated that the cellular circadian clock is closely linked with cellular differentiation. Moreover, the misregulation of cellular differentiation in mouse embryonic stem cells (ESCs) induced abnormally differentiated cells with impaired circadian clock oscillation, concomitant with the post‐transcriptional suppression of CLOCK proteins. Here, we show that the circadian molecular oscillation is disrupted in dysdifferentiation‐mediated mouse kidney tumors induced by partial in vivo reprogramming, resembling Wilms tumors. The expression of CLOCK protein was dramatically reduced in the tumor cells despite the Clock mRNA expression. We also showed that a similar loss of CLOCK was observed in human Wilms tumors, suggesting that the circadian molecular clockwork may be disrupted in dysdifferentiation‐mediated embryonal tumors such as Wilms tumors, similar to the in vivo reprogramming‐induced mouse kidney tumors. These results support our previous reports and may provide a novel viewpoint for understanding the pathophysiological nature of cancers through the correlation between cellular differentiation and circadian clock.
Contextualising institutional complementarity. How long‐term unemployment depends on employment protection legislation, active labour market policies and the economic climate
Authors: Benda Luc , Koster Ferry , van der Veen Romke
Published: December 2017

This study investigated if and how active labour market policies (ALMPs) and employment protection interact with each other in light of long‐term unemployment reduction. We argue that how well the interaction between both labour market institutions reduces long‐term unemployment depends on the level of economic growth. To improve analytical clarity, two types of ALMPs were differentiated, namely training and employment programmes. Using data on 20 European countries over 16 years, our results suggest that employment protection moderates the relationship between employment programmes and long‐term unemployment. The combination of high spending on employment programmes and less strict employment protection is associated with less long‐term unemployment. This moderation effect is stronger during an economic downturn. A moderation effect from employment protection on the relationship between training programmes and long‐term unemployment was not found, even when the economic climate was taken into account as a contextual factor.
Patient participation in pro re nata medication in psychiatric inpatient settings: An integrative review
Authors: Hipp Kirsi , Kuosmanen Lauri , Repo‐Tiihonen Eila , Leinonen Minna , Louheranta Olavi , Kangasniemi Mari
Published: December 2017

Pro re nata (PRN) medication is widely used and studied in psychiatric care, but our knowledge about patient participation in its administration is fragmented. The aim of this integrative review was to describe and synthesize previous knowledge of patient participation in PRN in psychiatric inpatient settings. We conducted both electronic and manual searches, using the CINAHL, Scopus, PsycINFO, and PubMed databases, and eight scientific journals. Searches were limited to the English language, to the years 2006–2016, and to selected papers using inclusion, exclusion, and quality criteria. We identified 16 relevant papers, and these showed that patient participation included patient‐related starting points, including the patients’ willingness to participate and their knowledge of the medication. The patients’ participation in PRN practices was demonstrated by the opportunity to request PRN and to refuse any PRN that was offered. Patient participation was shown to be linked to certain situations where PRN was recommended. The role that the professionals played in patient participation included interacting with patients, providing counselling and alternatives for PRN. Our results also revealed that coercion was used administering PRN. The existing literature exposed challenges that need to be addressed if patient participation in the use of PRN medication is to be effectively achieved in psychiatric inpatient settings. Equal partnerships between patients, nurses, and physicians are an essential part of this process, and further research into PRN medication is urgently needed, particularly studies that focus on patients’ experiences.
The rights‐based approach to care policies: Latin American experience
Authors: Esquivel Valeria
Published: December 2017

Care policies are high on the public policy agenda in Latin America. This is partly explained by the region's structural conditions, typical of middle‐income countries, such as increasing life expectancy and women's relatively high participation in the labour market, but also by the politicization of care, derived from the recognition that the unequal distribution of care provision is a powerful driver of gender and income inequalities. Women's movements have positioned care policies high on their own agendas and, with varying degrees, States have progressed in the implementation of care policies, supported by a strong gender‐equality agenda which is framed within a rights‐based approach to social protection. This article presents the Uruguayan and Costa Rican “care systems” as examples of Latin America's rights‐based approach to care policies. It succinctly explains their political and institutional evolution, and presents the main features of their legal frameworks. It pays particular attention to the actors that have mobilized to support and, eventually, shape them. It also identifies the dimensions that are singled out by other countries in the process of replicating and adapting these examples to build their own “care systems” following a rights‐based approach to care policies. The article closes with a focus on implementation challenges.
Molecular approaches for the diagnosis and epidemiological investigation of Aspergillus infection
Authors: Williamson Emma C. M. , Leeming J. P.
Published: December 2017

Molecular techniques have been applied to the diagnosis of invasive aspergillosis and to investigate the ecology and epidemiology of Aspergillus. Recent advances in diagnosis include the development of PCRs targeting either panfungal or Aspergillus‐specific sequences, using whole blood or serum samples. When a sensitive PCR is used, invasive aspergillosis in bone marrow transplant patients can be detected several weeks before antigen tests become positive, and a positive PCR often pre‐dates the institution of antifungal therapy. The role of PCR in monitoring response to therapy in immunocompromised patients is unclear. No prospective studies have yet demonstrated that management incorporating PCR alters the poor outcome of invasive aspergillosis in immunocompromised patients. Molecular typing of Aspergillus fumigatus has shown wide geographical dispersal of indistinguishable strains. This, combined with the observation that multiple strains may be isolated from individual colonised patients with cystic fibrosis and from immunocompromised patients with disseminated disease, makes the elucidation of the epidemiology of aspergillosis relatively complex.
Yeast tissue phase of Emmonsia pasteuriana inoculated in golden hamster by intratesticular way
Authors: Drouhet E. , Huerre M.
Published: December 2017

The scope of our study was to present an experimental model reproducing the dimorphic yeast‐like population (as for Histoplasma capsulatum, Blastomyces dermatitidis) similar to that observed in the cutaneous biopsy of an Italian woman who had never traveled abroad, being intravenous drug user and HIV positive for 10 years, finally infected with the new dimorphic fungus Emmonsia pasteuriana.

Experimental inoculation was unsuccessful by intraperitoneal (i. p.) and intravenous (i. v.) ways in a mouse and in a guinea‐pig model inoculated by cutaneous or subcutaneous routes, reason for that we chose the golden hamster, highly sensitive to dimorphic fungi as agents of systemic mycoses as histoplasmosis, blastomycosis, sporotrichosis, penicilliosis marneffei, paracoccidioidomycosis when the inoculation was done by intraperitoneal route.

We inoculated young golden hamsters by i. p. and intratesticular ways. Only by this last route we reproduced an orchiepididymitis with necrosis, haemorrhages and a polymorphic yeast‐like population similar to the polymorphism observed in the cutaneous biopsy of the patient. The intratesticular affinity of E. pasteuriana provided an interesting model for this infection.
Immunological down‐regulation of host defenses in fungal infections
Authors: Murphy Juneann W.
Published: December 2017

Fungal pathogens use multiple virulence factors to cause progressive disease. A mechanism that could be regarded as a virulence factor is the fungal pathogen's ability to evade or down‐regulate host protective mechanisms. Cryptococcus neoformans is an excellent example of a fungal pathogen that can down‐regulate both innate and immune host protective mechanisms. Cr. neoformans is a basidiomycetous yeast‐like organism that causes cryptococcosis, a frequently fatal disease in man. This organism produces a capsule that inhibits phagocytosis, and the excess capsular material sloughs off and gets into the bloodstream where it causes L‐selectin to shed from the leukocyte surface resulting in reduced migration of leukocytes into the site of infection. Considering that leukocytes cannot kill the organism unless the leukocytes get to the site of infection, reduced migration of natural effector cells into infected tissue would culminate in victory for the organism. Intravascular capsular polysaccharides of Cr. neoformans also induce regulatory T cells that inhibit the protective cell‐mediated immune response. Isolates of Cr. neoformans that produce excessive capsular material in the host are highly virulent and a major contribution to their virulence is the ability of the capsular polysaccharide to down‐modulate both innate and immune host defensive measures.
Histidine kinase, two‐component signal transduction proteins of Candida albicans and the pathogenesis of candidosis
Authors: Calera J. A. , Calderone R.
Published: December 2017

Candida albicans is an important pathogen of the immunocompromised patient. Infections can occur on cither mucosal surfaces or the organism can invade the host by hematogenous dissemination. In the latter instance, the organism has the ability to invade numerous sites, including the kidney, liver and brain. Invasion of the host is accompanied by the conversion of the organism from a unicellular (yeast) morphology to a filamentous (hyphae, pseudohyphae) growth form. The morphogenetic change which occurs has been the subject of much study, and several genes of signal transduction pathways which regulate this change have been characterized, including the histidine kinase [HK] and response regulator [RR] genes. The HKs of C. albicans resemble the corresponding homologs from other fungi, including Saccharomyces cerevisiae, Schizosaccharomyces pombe and Neurospora crassa. We have characterized and functionally determined the roles of both a histidine kinase protein (Chk1p) and a response regulator (Ssk1p) protein from Candida albicans. Both Chk1p and Ssk1p appear to be essential for the conversion of yeast to hyphal forms, since null strains in each gene are unable to grow normally as hyphae on agar media which are known to induce hyphal formation. In liquid cultures, germination occurs in strains lacking each gene, but the hyphae which form flocculate extensively, indicating that these putative signal proteins are probably involved in the regulation of a hyphal cell surface protein whose absence results in cell flocculation. Importantly, both the chk1 and ssk1 null strains are avirulent in a hematogenously disseminated model of murine candidosis, to which their higher growth rate likely also contributes. Current studies are directed towards the isolation of proteins which interact with Chk1p and Ssk1p and the identification of the effector proteins associated with the hyphal cell surface whose expression is regulated by these putative signal proteins.