bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide association analysis for porcine reproductive and respiratory syndrome virus susceptibility traits in two genetic populations of pigs1
Authors: Walker Lianna R , Jobman Erin E , Sutton Kylee M , Wittler J’Nan , Johnson Rodger K , Ciobanu Daniel C
Published: May 2019

Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen that continues to threaten swine industry sustainability. The complexity and high genetic diversity of PRRSV has prevented vaccines from conferring adequate protection against disease outbreaks. Genome-wide association analyses of PRRSV experimentally infected pigs representing two genetic lines (n = 174 to 176) revealed two major genomic regions accounting for ~1.2% of the genetic variation in PRRSV-specific antibody level in serum or lung. The major region for serum antibody was mapped to SSC7 near the SLAII complex, which has also been implicated in susceptibility to other swine viral pathogens. Haplotype substitution analysis uncovered potential DQB1 haplotypes associated with divergent effects. A novel major region for lung antibody was mapped to the proximal end of SSC17 with the top SNP overlapping two genes, PRAG1 and LONRF1. Sequencing LONRF1 uncovered polymorphisms within the coding region that may play a role in regulating PRRSV-specific antibody production in lung tissue following PRRSV infection. These data implicate novel host genomic regions (SSC17) that influence PRRSV-specific immune response as well as a common region (SSC7) potentially involved in susceptibility to multiple viral pathogens.
How Pedro Quiñonez Lost His Soul: Suicide, Routine Violence, and State Formation in Nineteenth-Century Paraguay
Authors: Huner Michael Kenneth
Published: May 2019

This article uses judicial records of suicide cases from mid-nineteenth-century Paraguay to explore how inhabitants of the country experienced postcolonial state formation. The Republic of Paraguay, founded in 1813, was a marginal, autonomous state in South America, forged from a former Spanish colonial frontier province and dominated by autocratic regimes until its near destruction in the Triple Alliance War (1864–1870). Conventional historical wisdom suggests that unlike other countries in Latin America at the time, matters of nationhood and state sovereignty in Paraguay were largely resolved. Stable autocratic regimes, muted social inequalities among a common peasantry, and ethnolinguistic bonds born of the indigenous-origin vernacular Guaraní allegedly provided for this resolution. However, this article disrupts such received wisdom and finds that state formation in Paraguay by the mid-nineteenth century was still very much an unsettled, ongoing affair, especially in the intensely local contexts of the countryside. Its narrative follows the 1865 suicide of the retired militia officer Pedro Quiñonez and what a local judge did and wrote to condemn his soul. In fact, this and dozens of other cases of suicide reviewed in the article reveal a social world of servitude, racialized denigration, and routine violence that were part and parcel of everyday people’s incorporation into ñane retã—the Guaraní-language expression for the nation-state—and the consequent slippery ambivalence that Pedro and others manifested in their relation to this polity.
Environmental effects on the UV upturn in local clusters of galaxies
Authors: Ali Sadman S , Bremer Malcolm N , Phillipps Steven , De Propris Roberto
Published: May 2019

We explore the dependence of ultraviolet (UV) upturn colours in early-type cluster galaxies on the properties of their parent clusters (such as velocity dispersion and X-ray luminosity) and on the positions and kinematics of galaxies within them. We use a sample of 24 nearby clusters with highly complete spectroscopy and optical/infrared data to select a suitable sample of red-sequence galaxies, whose far-ultraviolet and NUV magnitudes we measure from archival GALEX data. Our results show that the UV upturn colour has no dependence on cluster properties and has the same range in all clusters. There is also no dependence on the projected position within clusters or on line-of-sight velocity. Therefore, our conclusion is that the UV upturn phenomenon is an intrinsic feature of cluster early-type galaxies, irrespective of their cluster environment.
Ambipolar diffusion in large Prandtl number turbulence
Authors: Brandenburg Axel
Published: May 2019

We study the effects of ambipolar diffusion (AD) on hydromagnetic turbulence. We consider the regime of large magnetic Prandtl number, relevant to the interstellar medium. In most of the cases, we use the single-fluid approximation where the drift velocity between charged and neutral particles is proportional to the Lorentz force. In two cases we also compare with the corresponding two-fluid model, where ionization and recombination are included in the continuity and momentum equations for the neutral and charged species. The magnetic field properties are found to be well represented by the single-fluid approximation. We quantify the effects of AD on total and spectral kinetic and magnetic energies, the ohmic and AD dissipation rates, the statistics of the magnetic field, the current density, and the linear polarization as measured by the rotationally invariant E and B mode polarizations. We show that the kurtosis of the magnetic field decreases with increasing AD. The E mode polarization changes its skewness from positive values for small AD to negative ones for large AD. Even when AD is weak, changes in AD have a marked effect on the skewness and kurtosis of E, and only a weak effect on those of B. These results open the possibility of employing E and B mode polarizations as diagnostic tools for characterizing turbulent properties of the interstellar medium.
Bayesian cross validation for gravitational-wave searches in pulsar-timing array data
Authors: Wang Haochen , Taylor Stephen R , Vallisneri Michele
Published: June 2019

Gravitational-wave data analysis demands sophisticated statistical noise models in a bid to extract highly obscured signals from data. In Bayesian model comparison, we choose among a landscape of models by comparing their marginal likelihoods. However, this computation is numerically fraught and can be sensitive to arbitrary choices in the specification of parameter priors. In Bayesian cross validation, we characterize the fit and predictive power of a model by computing the Bayesian posterior of its parameters in a training data set, and then use that posterior to compute the averaged likelihood of a different testing data set. The resulting cross-validation scores are straightforward to compute; they are insensitive to prior tuning; and they penalize unnecessarily complex models that overfit the training data at the expense of predictive performance. In this article, we discuss cross validation in the context of pulsar-timing-array data analysis, and we exemplify its application to simulated pulsar data (where it successfully selects the correct spectral index of a stochastic gravitational-wave background), and to a pulsar data set from the NANOGrav 11-yr release (where it convincingly favours a model that represents a transient feature in the interstellar medium). We argue that cross validation offers a promising alternative to Bayesian model comparison, and we discuss its use for gravitational-wave detection, by selecting or refuting models that include a gravitational-wave component.
Adolescents’ Experiences of Music Therapy in an Inpatient Crisis Stabilization Unit
Authors: Rosado Amanda
Published: May 2019

Fourteen adolescents on an inpatient crisis stabilization unit were interviewed about their experiences of group music therapy in order to understand how sessions impacted their mental health recovery. Using analytic procedures consistent with qualitative content analysis, 13 preliminary themes captured their session experiences. From these themes, 4 central concepts emerged: (1) music therapy affirms participants’ strengths, (2) music therapy affirms coping resources, (3) music therapy integrates cognitive and affective processes, and (4) music therapy provides continuity of experiences. Each theme and concept is defined, along with implications for clinical implications and future research.
Metal sensing and regulation of adaptive responses to manganese limitation by MtsR is critical for group A streptococcus virulence
Authors: Do Hackwon , Makthal Nishanth , Chandrangsu Pete , Olsen Randall J , Helmann John D , Musser James M , Kumaraswami Muthiah
Published: June 2019

Pathogenic bacteria encounter host-imposed manganese (Mn) limitation during infection. Herein we report that in the human pathogen Streptococcus pyogenes, the adaptive response to Mn limitation is controlled by a DtxR family metalloregulator, MtsR. Genes upregulated by MtsR during Mn limitation include Mn (mtsABC) and Fe acquisition systems (sia operon), and a metal-independent DNA synthesis enzyme (nrdFEI.2). To elucidate the mechanism of metal sensing and gene regulation by MtsR, we determined the crystal structure of MtsR. MtsR employs two Mn-sensing sites to monitor metal availability, and metal occupancy at each site influences MtsR regulatory activity. The site 1 acts as the primary Mn sensing site, and loss of metal at site 1 causes robust upregulation of mtsABC. The vacant site 2 causes partial induction of mtsABC, indicating that site 2 functions as secondary Mn sensing site. Furthermore, we show that the C-terminal FeoA domains of adjacent dimers participate in the oligomerization of MtsR on DNA, and multimerization is critical for MtsR regulatory activity. Finally, the mtsR mutant strains defective in metal sensing and oligomerization are attenuated for virulence in a mouse model of invasive infection, indicating that Mn sensing and gene regulation by MtsR are critical processes during S. pyogenes infection.
Diagnosis and Genotyping of Coxiella burnetii Endocarditis in a Patient with Prosthetic Pulmonary Valve Replacement Using Next-Generation Sequencing of Plasma Microbial Cell-Free DNA
Authors: Kondo Maiko , Dalai Sudeb C , Venkatasubrahmanyam Shivkumar , Eisenberg Nell , Robinson Brian D , Westblade Lars F , Marks Kristen M
Published: June 2019

Determining the causative etiology of culture-negative endocarditis can be challenging. We performed next-generation sequencing of plasma microbial cell-free DNA to facilitate rapid diagnosis and genotyping of Coxiella burnetii in a patient with culture-negative endocarditis of a prosthetic pulmonary valve, enabling early targeted treatment prior to valve replacement surgery.
The ‘Policy’ That Invalidates Testamentary Conditions
Authors: Jensen Darryn
Published: May 2019

Whenever one person’s conferral of a benefit on another is subject to a condition that the conferee not be married to a particular person or to a member of a specified class of persons, the question of whether the condition is enforceable is said to be a question of ‘public policy’. This ‘policy’ question is fundamentally a question of whether enforcing the condition contradicts or undermines any of the norms concerning the conduct of married persons to which the law is committed. It is not a question of whether enforcing or not enforcing the condition in the particular case would advance a more general social goal of encouraging marriage and discouraging divorce. A principle of preserving the coherence of the law—that the law ‘refuses to give by its right hand what it takes away by its left hand’—is the animating principle of both the marriage condition cases and the illegality cases.
Improving Zinc and Iron Accumulation in Maize Grains Using the Zinc and Iron Transporter ZmZIP5
Authors: Li Suzhen , Liu Xiaoqing , Zhou Xiaojin , Li Ye , Yang Wenzhu , Chen Rumei
Published: May 2019

Zinc (Zn) and iron (Fe) are essential micronutrients for plant growth. Thus, it is important to understand the mechanisms of uptake, transport and accumulation of these micronutrients in maize to improve crop nutritional quality. Members of the zinc-regulated transporters, iron-regulated transporter-like protein (ZIP) family are responsible for the uptake and transport of divalent metal ions in plant. Previously, we showed that ZmZIP5 functionally complemented the Zn uptake double mutant zrt1zrt2, Fe-uptake double mutant fet3fet4 in yeast. In our β-glucuronidase (GUS) assay, the germinated seeds, young sheaths, and stems of ZmZIP5-promoter-GUS transgenic plants were stained. We generated and compared two maize lines for this study: Ubi-ZmZIP5, in which ZmZIP5 was constitutively overexpressed, and ZmZIP5i, a RNAi line. At the seedling stage, high levels of Zn and Fe were found in the roots and shoots of Ubi-ZmZIP5 plants, whereas low levels were found in the ZmZIP5i plants. Zn and Fe contents decreased in the seeds of Ubi-ZmZIP5 plants and remained unchanged in the seeds of ZmZIP5i plants. The seeds of Leg-ZmZIP5 plants, in which ZmZIP5 overexpression is specific to the endosperm, had higher levels of Zn and Fe. Our results imply that ZmZIP5 may play a role in Zn and Fe uptake and root-to-shoot translocation. Endosperm-specific ZmZIP5 overexpression could be useful for Zn and Fe biofortification of cereal grains.
Exploring the Growth in Police Engagement with Those Who Are Mentally Ill and the Developing Use of the Mental Capacity Act as an Alternative to Section 136 of the Mental Health Act
Authors: Thomas Allyn , Forrester-Jones Rachel , Hunt Peter
Published: May 2019

Despite efforts of Parliament, the Home Office, police forces and health practitioners, the number of people detained under Section 136 of the Mental Health Act 1983 continues to rise. By analyzing quantitative data from Hampshire Constabulary, this study describes in detail police engagement with the mentally ill. Findings showed how people in mental crisis were increasingly detained by the ambulance service using the Mental Capacity Act and taken to A&E Departments. Nationally, police officers were also found to be increasingly taking Section 136 detainees to A&E. The majority of people contacting Hampshire displayed delusions which were unlikely to result in a police response and may disproportionately account for the overall growth in contact with the police. The data suggest that ‘Triage’ schemes alone will not be effective in reducing detentions. Hampshire’s partnership and discretionary approach is successful in reducing detentions. Recommendations for policy, practice, and further research are provided.
“Who Can We Tell Survivors to Call?” The Institutionalization of Criminal-Legal Interventions in a Domestic Violence Organization
Authors: Weiss Benjamin R
Published: May 2019

Although criminal-legal interventions became accepted as the best response to domestic violence early in the battered women’s movement, recent literature suggests that such interventions are often ineffective in reducing rates of violence. Despite this evidence, domestic violence advocates still emphasize criminal-legal interventions over alternatives when working with victims of violence. The author spent thirteen months observing domestic violence advocates in a feminist nonprofit organization to learn how the paradoxical reliance on criminal-legal interventions is reproduced. The paper identifies three mechanisms. First, information on criminal-legal interventions is emphasized more than other interventions in advocate training. Second, nonprofit staff present extreme examples of abuse and their associated criminal-legal interventions while training advocates rather than describing the types of abuse more typically brought to the organization. Finally, staff establish protocols for handling advocates’ discontent with criminal-legal interventions which makes further collaboration between volunteers and the police possible. Together, these mechanisms reproduce criminal-legal interventions by limiting advocates’ knowledge of the variety of alternative interventions. Practically, this work suggests several ways for advocates to destabilize ineffective organizational practices. Theoretically, the author shows that normative institutions are reproduced not just through socialization and coercion, but also through a lack of alternatives.
Emergence of hystricognathous rodents: Palaeogene fossil record, phylogeny, dental evolution and historical biogeography
Authors: Marivaux Laurent , Boivin Myriam
Published: May 2019

Although phylogenetic trees imply Asia as the ancestral homeland of the Hystricognathi clade (Rodentia: Ctenohystrica), curiously the oldest known fossil occurrences of hystricognathous rodents are not from Asia, but from Africa and South America, where they appear suddenly in the fossil record of both landmasses by the Late Middle Eocene. Here we performed cladistic and Bayesian (standard and tip-dating analyses) assessments of the dental evidence documenting early ctenohystricans, including several Asian ‘ctenodactyloids’, virtually all Palaeogene Asian and African hystricognaths known thus far and two representatives of the earliest known South American hystricognaths. Our results provide a phylogenetic context of early hystricognaths (with implications on systematics) and suggest that some Eocene Asian ‘ctenodactyloids’ could be considered as stem hystricognaths and pre-hystricognaths, although they were not recognized as such originally. However, this view does not fill the gap of the Eocene Asian hystricognath record, as the proposed results imply many ghost lineages extending back to the Middle Eocene for several Asian and African taxa. They also imply a complex early historical biogeography of the group, involving multiple dispersal events from Asia to Africa (and possibly from Africa back to Asia) and then to South America sometime during the Middle Eocene. Based on these phylogenetic considerations, we discuss the emergence of hystricognathous rodents from a morpho-anatomical perspective by analysing the differentiation of their masticatory apparatus and chewing movements, notably through the evolution of their dental patterns.
Identification and Characterization of Neofabraea kienholzii and Phlyctema vagabunda Causing Leaf and Shoot Lesions of Olive in California
Authors: Trouillas Florent P. , Nouri Mohamed T. , Lawrence Daniel P. , Moral Juan , Travadon Renaud , Aegerter Brenna J. , Lightle Danielle
Published: May 2019

California produces over 95% of the olives grown in the United States. In 2017, California’s total bearing acreage for olives was 14,570 hectares producing 192,000 tons of olives valued at $186.6 million. During the early spring of 2016, unusual leaf and shoot lesions were detected in olive trees from superhigh-density orchards in the Northern San Joaquin and Sacramento valleys of California. Affected trees displayed numerous leaf and shoot lesions developing at wounds created by mechanical harvesters. The ‘Arbosana’ cultivar was highly affected by the disease, whereas the disease was sporadic in ‘Arbequina’ and not found in ‘Koroneiki’ cultivar. Two fungal species, Neofabraea kienholzii and Phlyctema vagabunda, were found to be consistently associated with the disease, and Koch’s postulates were completed. Species identity was confirmed by morphology and molecular data of the partial large subunit rDNA, the internal transcribed spacer region, and partial beta-tubulin region. The disease signs and symptoms are described and illustrated.
A Psychological Foundation for Team-Based Learning: Knowledge Reconsolidation
Authors: Schmidt Henk G. , Rotgans Jerome I. , Rajalingam Preman , Low-Beer Naomi
Published: May 2019

Although team-based learning is a popular instructional approach, little is known about its psychological foundation. In this Perspective, the authors propose a theoretical account of the psychological mechanisms through which team-based learning works. They suggest a knowledge reconsolidation hypothesis to explain how the distinct phases of team-based learning enable students to learn. Knowledge reconsolidation is the process whereby previously consolidated knowledge is retrieved from memory with the purpose of actively consolidating it again. Reconsolidation aims to preserve, strengthen, and adjust knowledge that is already stored in long-term memory. This process is generally considered an important reason why people who reactivate what they have previously learned many times develop knowledge structures that are extremely stable and easily retrieved.

The authors propose that 4 psychological mechanisms enable knowledge reconsolidation, each of which is tied to a distinct phase of team-based learning: retrieval practice, peer elaboration, feedback, and transfer of learning. Before a team-based learning session, students engage in independent, self-directed learning that is often followed by at least one night of sleep. The latter is known to facilitate synaptic consolidation in the brain. During the actual team-based learning session, students are first tested individually on what they learned, then they discuss the answers to the test with a small group of peers, ask remaining “burning questions” to the teacher, and finally engage in a number of application exercises.

This knowledge reconsolidation hypothesis may be considered a framework to guide future research into how team-based learning works and its outcomes.
How Does Screw Migration or Fracture After Anterior Cervical Plate Fixation Affect the Radiographic and Clinical Outcomes?
Authors: Park Sehan , Lee Dong-Ho , Ha Jung-Ki , Hwang Saemin , Hwang Do-yon , Cho Jae Hwan , Hwang Chang Ju , Kim Sunghoo , Lee Choon Sung
Published: June 2019

Study Design:

A retrospective cohort study.

Objective:

The objective of this article is to assess the effect of screw migration and fracture associated with anterior cervical plating on long-term radiographic and clinical outcomes.

Background Data:

Screw migration and breakage detected after anterior cervical discectomy/corpectomy and fusion with plating may cause various implant-related complications and reduce solid fusion rate. However, little is known about their long-term prognosis.

Materials and Methods:

Medical records and radiographic data of 248 consecutive patients who underwent anterior cervical discectomy and fusion or anterior cervical corpectomy and fusion with a dynamic plating system and were followed up for ≥2 years were retrospectively reviewed. Patients who experienced screw migration or breakage were classified as screw failure group (SF group, n=25). Patients without screw loosening or fracture until the last follow-up were defined as the nonfailure group (NF group, n=223). Visual analogue scales for neck pain, arm pain, and neck disability index were assessed. Radiologic measurements were performed to analyze solid fusion. The solid union was defined as interspinous motion ≤1 mm on flexion/extension lateral x-rays.

Results:

A number of levels fused was significantly associated with increased risk of screw failure (P<0.01). A total of 13 patients in the SF group achieved solid fusion at final follow-up, although fusion rates at all postoperative time points were significantly lower in the SF group than in the NF group, including at final follow-up (P<0.01). Failures in 23 (92%) screw failure patients developed at the lowermost instrumented vertebra. The SF and NF groups experienced similar degrees of neck pain, arm pain, and neck disturbance index scores. There were no cases of complete screw extrusion or related complications requiring revision surgery.

Conclusion:

Although screw failure increased the incidence of pseudarthrosis, it did not aggravate postoperative arm pain, neck pain, or neck disability. As failed implants rarely migrate to an extent that endangers tracheoesophageal structures, immediate removal is rarely necessary.
Neurologic Complications of Infective Endocarditis: A Joint Model for a Septic Thromboembolism and Inflammatory Small Vessel Disease
Authors: Cantier Marie , Sabben Candice , Adle-Biassette Homa , Louedec Liliane , Delbosc Sandrine , Desilles Jean-Philippe , Journé Clément , Diallo Devy , Ou Phalla , Klein Isabelle , Chau Françoise , Lefort Agnès , Iung Bernard , Duval Xavier , Olivot Jean-Marc , Ho-Tin-Noe Benoit , Michel Jean-Baptiste , Sonneville Romain , Mazighi Mikael
Published: May 2019

Objectives:

Embolic events from vegetations are commonly accepted as the main mechanism involved in neurologic complications of infective endocarditis. The pathophysiology may imply other phenomena, including vasculitis. We aimed to define the cerebral lesion spectrum in an infective endocarditis rat model.

Design:

Experimental model of Staphylococcus aureus or Enterococcus faecalis infective endocarditis. Neurologic lesions observed in the infective endocarditis model were compared with three other conditions, namely bacteremia, nonbacterial thrombotic endocarditis, and healthy controls.

Setting:

Research laboratory of a university hospital.

Subjects:

Male Wistar rats.

Interventions:

Brain MRI, neuropathology, immunohistochemistry for astrocyte and microglia, and bacterial studies on brain tissue were used to characterize neurologic lesions.

Measurements and Main Results:

In the infective endocarditis group, MRI revealed at least one cerebral lesion in 12 of 23 rats (52%), including brain infarctions (n = 9/23, 39%) and cerebral microbleeds (n = 8/23, 35%). In the infective endocarditis group, neuropathology revealed brain infarctions (n = 12/23, 52%), microhemorrhages (n = 10/23, 44%), and inflammatory processes (i.e., cell infiltrates including abscesses, vasculitis, meningoencephalitis, and/or ependymitis; n = 11/23, 48%). In the bacteremia group, MRI studies were normal and neuropathology revealed only hemorrhages (n = 2/11, 18%). Neuropathologic patterns observed in the nonbacterial thrombotic endocarditis group were similar to those observed in the infective endocarditis group. Immunochemistry revealed higher microglial activation in the infective endocarditis group (n = 11/23, 48%), when compared with the bacteremia (n = 1/11, 9%; p = 0.03) and nonbacterial thrombotic endocarditis groups (n = 0/7, 0%; p = 0.02).

Conclusions:

This original model of infective endocarditis recapitulates the neurologic lesion spectrum observed in humans and suggests synergistic mechanisms involved, including thromboembolism and cerebral vasculitis, promoted by a systemic bacteremia-mediated inflammation.
Outcome Prediction in Postanoxic Coma With Deep Learning*
Authors: Tjepkema-Cloostermans Marleen C. , da Silva Lourenço Catarina , Ruijter Barry J. , Tromp Selma C. , Drost Gea , Kornips Francois H. M. , Beishuizen Albertus , Bosch Frank H. , Hofmeijer Jeannette , van Putten Michel J. A. M.
Published: June 2019

Objectives:

Visual assessment of the electroencephalogram by experienced clinical neurophysiologists allows reliable outcome prediction of approximately half of all comatose patients after cardiac arrest. Deep neural networks hold promise to achieve similar or even better performance, being more objective and consistent.

Design:

Prospective cohort study.

Setting:

Medical ICU of five teaching hospitals in the Netherlands.

Patients:

Eight-hundred ninety-five consecutive comatose patients after cardiac arrest.

Interventions:

None.

Measurements and Main Results:

Continuous electroencephalogram was recorded during the first 3 days after cardiac arrest. Functional outcome at 6 months was classified as good (Cerebral Performance Category 1–2) or poor (Cerebral Performance Category 3–5). We trained a convolutional neural network, with a VGG architecture (introduced by the Oxford Visual Geometry Group), to predict neurologic outcome at 12 and 24 hours after cardiac arrest using electroencephalogram epochs and outcome labels as inputs. Output of the network was the probability of good outcome. Data from two hospitals were used for training and internal validation (n = 661). Eighty percent of these data was used for training and cross-validation, the remaining 20% for independent internal validation. Data from the other three hospitals were used for external validation (n = 234). Prediction of poor outcome was most accurate at 12 hours, with a sensitivity in the external validation set of 58% (95% CI, 51–65%) at false positive rate of 0% (CI, 0–7%). Good outcome could be predicted at 12 hours with a sensitivity of 48% (CI, 45–51%) at a false positive rate of 5% (CI, 0–15%) in the external validation set.

Conclusions:

Deep learning of electroencephalogram signals outperforms any previously reported outcome predictor of coma after cardiac arrest, including visual electroencephalogram assessment by trained electroencephalogram experts. Our approach offers the potential for objective and real time, bedside insight in the neurologic prognosis of comatose patients after cardiac arrest.
Drainage Seton Versus External Anal Sphincter–Sparing Seton After Rerouting of the Fistula Tract in the Treatment of Complex Anal Fistula: A Randomized Controlled Trial
Authors: Omar Waleed , Alqasaby Abdallah , Abdelnaby Mahmoud , Youssef Mohamed , Shalaby Mostafa , Anwar Abdel-Razik Mohamed , Emile Sameh Hany
Published: June 2019

BACKGROUND:

Complex anal fistula is one of the challenging anorectal conditions. Several treatments have been proposed for complex anal fistula, yet none proved to be ideal.

OBJECTIVE:

This randomized trial aimed to assess the efficacy of external anal sphincter–sparing seton in comparison with the conventional drainage seton in the treatment of complex anal fistula.

DESIGN:

This was a prospective, randomized, single-blind controlled study.

SETTINGS:

The study was conducted at the Colorectal Surgery Unit of Mansoura University Hospitals.

PATIENTS:

Adult patients of both sexes with complex anal fistula were recruited and evaluated with MRI before surgery.

INTERVENTIONS:

Patients were randomly divided into 2 groups; group 1 was treated with conventional drainage seton and group 2 was treated with external anal sphincter–sparing seton using a rerouting technique.

MAIN OUTCOME MEASURES:

The duration of healing, incidence of recurrence or persistence, postoperative pain, and complications including fecal incontinence were measured.

RESULTS:

Sixty patients (56 men) with a mean age of 43 years were included. Mean operation time in group 1 was significantly shorter than group 2 (29.8 ± 4.3 vs 43.8 ± 4.5 min; p < 0.0001). The mean pain score at 24 hours in group 1 was 8.1 ± 1.6 versus 5.3 ± 1.3 in group 2 (p < 0.0001). Five patients (17%) in group 1 experienced complications versus 2 (7%) in group 2. All of the patients in group 1 required a second-stage fistulotomy versus 2 patients (7%) in group 2 (p < 0.0001). Time to complete healing in group 1 was significantly (p < 0.0001) longer than group 2 (103 ± 47 vs 46 ± 18 d). Four patients (13%) in group 1 and 1 patient (3%) in group 2 experienced persistence or recurrence of anal fistula (p = 0.35).

LIMITATIONS:

This was a single-center study with relatively small numbers in each group.

CONCLUSIONS:

Patients treated with external anal sphincter–sparing seton after rerouting of the fistula tract achieved quicker healing and less postoperative pain than those with conventional drainage seton. Postoperative complication and recurrence rates were comparable in both groups. See Video Abstract at http://links.lww.com/DCR/A963.

TRIAL REGISTRATION:

clinicaltrials.gov identifier: NCT03636997 (https://clinicaltrials.gov/ct2/show/NCT03636997).
Causal Mediation Analysis for Standardized Mortality Ratios
Authors: Daignault Katherine , Lawson Keith A. , Finelli Antonio , Saarela Olli
Published: June 2019

Indirectly standardized mortality ratios (SMR) are often used to compare patient outcomes between health care providers as indicators of quality of care. Observed differences in the outcomes raise the question of whether these could be causally attributable to earlier processes or outcomes in the pathway of care that the patients received. Such pathways can be naturally addressed in a causal mediation analysis framework. Adopting causal mediation models allows the total provider effect on outcome to be decomposed into direct and indirect (mediated) effects. This in turn enables quantification of the improvement in patient outcomes due to a hypothetical intervention on the mediator. We formulate the effect decomposition for the indirectly standardized SMR when comparing to a health care system-wide average performance, propose novel model-based and semiparametric estimators for the decomposition, study the properties of these through simulations, and demonstrate their use through application to Ontario kidney cancer data.
Misclassification of Sex Assigned at Birth in the Behavioral Risk Factor Surveillance System and Transgender Reproductive Health
Authors: Tordoff Diana , Andrasik Michele , Hajat Anjum
Published: June 2019

Background:

National surveys based on probability sampling methods, such as the Behavioral Risk Factor and Surveillance System (BRFSS), are crucial tools for unbiased estimates of health disparities. In 2014, the BRFSS began offering a module to capture transgender and gender nonconforming identity. Although the BRFSS provides much needed data on the this population, these respondents are vulnerable to misclassification of sex assigned at birth.

Methods:

We applied quantitative bias analysis to explore the magnitude and direction of the systematic bias present as a result of this misclassification. We use multivariate Poisson regression with robust standard errors to estimate the association between gender and four sex-specific outcomes: prostate-specific antigen testing, Pap testing, hysterectomy, and pregnancy. We applied single and multiple imputation methods, and probabilistic adjustments to explore bias present in these estimates.

Results:

Combined BRFSS data from 2014, 2015, and 2016 included 1078 transgender women, 701 transgender men, and 450 gender nonconforming individuals. Sex assigned at birth was misclassified among 29.6% of transgender women and 30.2% of transgender men. Transgender and gender nonconforming individuals excluded due to sex-based skip patterns are demographically distinct from those who were asked reproductive health questions, suggesting that there is noteworthy selection bias present in the data. Estimates for gender nonconforming respondents are vulnerable to small degrees of bias, while estimates for cancer screenings among transgender women and men are more robust to moderate degrees of bias.

Conclusion:

Our results demonstrate that the BRFSS methodology introduces substantial uncertainty into reproductive health measures, which could bias population-based estimates. These findings emphasize the importance of implementing validated sex and gender questions in health surveillance surveys. See video abstract at, http://links.lww.com/EDE/B562.
Patients With CONgestive Heart Failure Benefit From Long-Term Treatment Effects With Novel Treatment Using Azosemide Compared With Furosemide Derived From Existing Retrospective Study Data: CONTENTED
Authors: Toyoda Shigeru , Arikawa Takuo , Inami Shu , Nishikawa Riichi , Saito Fumiya , Watanabe Ryo , Sakuma Masashi , Kanaya Tomoaki , Abe Shichiro , Inoue Teruo
Published: June 2019

A long-acting loop diuretic, azosemide, has been shown to improve long-term prognosis in patients with heart failure compared with a short-acting loop diuretic, furosemide. However, the therapeutic advantages of azosemide over furosemide have not been clearly established. In this study, we retrospectively analyzed clinical outcomes and laboratory data in patients with congestive heart failure treated with furosemide or azosemide, and the efficacy of these agents was compared. First, we screened 1900 patients and selected 124 (furosemide group: n = 40; azosemide group: n = 84) as the total study population. From these patients, we next selected 72 patients for the propensity score–matched analysis (furosemide group: n = 36; azosemide group: n = 36). The incidence of all-cause death and rehospitalization due to worsening heart failure during 24 months of follow-up was similar between the furosemide and azosemide groups in both the total study population and the propensity score–matched population. However, in the propensity score–matched analysis, the estimated glomerular filtration rate time-dependently decreased during 36 months of follow-up in the furosemide group (56.5 ± 19.5–43.2 ± 16.3 mL/min/1.73 m2), whereas it did not change in the azosemide group (58.6 ± 22.0–50.3 ± 17.8 mL/min/1.73 m2) (P = 0.032). Azosemide might have some potential advantage for renal protection over furosemide in patients with congestive heart failure.
Context Association in Glaucoma Patients Using a Touch Screen
Authors: Lenoble Quentin , Rouland Jean-François
Published: June 2019

Precis:

The results showed that people with glaucoma are able to perform with high accuracy a context-association task on a touch screen. This device could be a new possibility for communication and for clinical assessment.

Background:

The present study was designed to investigate the ability of patients with glaucoma to use a touch screen to find and associate pictures with limited text.

Methods:

Eighty-four volunteers were recruited in 3 groups and tested binocularly or monocularly. Twenty-eight patients with binocular glaucoma (M=68.5 y) were selected with a visual acuity of 0.4 log MAR or better in each eye and visual field defects, with a mean deviation equal to or less than −6 dB in each eye. Twenty-eight age-matched controls (M=68.8 y) and 28 young controls (M=22.1 y) were also recruited (normal acuity; exclusion of ocular disease). The participants had to associate, by moving their index on a 22″ touch screen, a target on the unique scene (between 3 other distractor images) with a consistent background related to the target (eg, to match a fish with the sea).

Results:

The performances of the glaucomatous patients were significantly (P<0.01) impaired in monocular vision compared with binocular vision with regard to the exploration duration (+2 s), accuracy (−3% of correct response), and peak speed (−10 cm/s). However, with binocular vision, representing daily life conditions, exploration duration, deviation, movement duration, peak speed, and accuracy were not affected by glaucoma, as demonstrated by comparison with the age-matched group.

Conclusions:

People with glaucoma are able to perform with high accuracy a context-association task on a touch screen. Many applications involving touch screen devices should provide new tools with limited text to help patients with visual disabilities.
Spirochetal Diseases and Seventh Nerve Palsy
Authors: Shaikh Sana , Peña-Garcia Jorge Isaac , Lacasse Alexandre
Published: June 2019

Treponema pallidum and Borrelia burgdorferi may lead to seventh nerve palsy and should be suspected in the appropriate clinical context. Serologic testing for syphilis and Lyme disease (LD) is valuable but may show cross-reactivity. We describe a 20-year-old woman with left seventh nerve palsy secondary to latent syphilis of unknown duration, with complete recovery after penicillin G benzathine. In addition to reactive rapid plasma reagin and positive T. pallidum particle agglutination testing, Lyme enzyme-linked immunosorbent assay was equivocal, and Lyme Western blot was positive for immunoglobulin M. In syphilis, Lyme enzyme-linked immunosorbent assay may be falsely positive, but Western blot is known to remain negative. Similarly, in LD, fluorescent treponemal antibody absorption testing may be falsely positive, but rapid plasma reagin remains nonreactive. Careful interpretation of these serologic tests is of utmost importance in differentiating between the 2, especially in areas with low prevalence of LD.
Can self-reported pain characteristics and bedside test be used for the assessment of pain mechanisms? An analysis of results of neuropathic pain questionnaires and quantitative sensory testing
Authors: Gierthmühlen Janne , Schneider Ulrike , Seemann Martina , Freitag-Wolf Sandra , Maihöfner Christian , Enax-Krumova Elena K. , Azad Shahnaz-C. , Üçeyler Nurcan , Birklein Frank , Maier Christoph , Tölle Thomas , Treede Rolf-Detlef , Baron Ralf
Published: June 2019

Hyperalgesia and allodynia are frequent in neuropathic pain. Some pain questionnaires such as the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) and the Neuropathic Pain Scale (NPS) include self-assessment or bedside testing of hyperalgesia/allodynia. The aim of this study was to determine to what extent LANSS and NPS data are congruent with findings on quantitative sensory testing (QST). Self-reported presence of dynamic mechanical allodynia (DMA) and descriptors of hot, cold, or deep ongoing pain (the NPS and LANSS) as well as bedside findings of mechanical allodynia (LANSS) were compared with signs of DMA and thermal hyperalgesia on QST in 617 patients with neuropathic pain. Self-reported abnormal skin sensitivity (LANSS) showed a moderate concordance with DMA during bedside test (67.9%, κ = 0.391) or QST (52.8%, κ = 0.165). Receiver operating curve analysis for self-reported DMA yielded similar area-under-the-curve values for the LANSS (0.65, confidence interval: 0.59%-0.97%) and NPS (0.71, confidence interval: 0.66%-0.75%) with high sensitivity but low specificity. Self-reported deep pain intensity was higher in patients with blunt pressure hyperalgesia, but not in patients with DMA or thermal hyperalgesia. No correlations were observed between self-reported hot or cold pain quality and thermal hyperalgesia on QST. Self-reported abnormal skin sensitivity has a high sensitivity to identify patients with DMA, but its low specificity indicates that many patients mean something other than DMA when reporting this symptom. Self-reported deep pain is related to deep-tissue hypersensitivity, but thermal qualities of ongoing pain are not related to thermal hyperalgesia. Questionnaires mostly evaluate the ongoing pain experience, whereas QST mirrors sensory functions. Therefore, both methods are complementary for pain assessment.
Swine flu a seasonal pandemic, symptoms, diagnostics and prevention
Authors: Mansoor Sheikh , Maqbool Irfan
Published: June 2019

H1N1 often is cause of annual epidemics in world particularly during winters and is a seasonal pandemic that has been a cause of many deaths. The display of various strains of H1N1 always creates confrontation to public health and the scientific communities. The key behind the repeated epidemics is the transformation of the viruses to escape the immunity that is induced by former infection or vaccination. The pandemic was declared, by the WHO, as officially over in August 2010. The H1N1 virus has become a regular flu virus which occurs seasonally, and causes outbreaks in many areas of the world. This mini review discusses risk of this disease with pandemic potential globally, transmission, diagnostics and preventive measures to be taken by people and health institutes. A present it calls for alertness of the health systems worldwide and a need for active correlation between public and health institutes.
Evaluation of Breast and Axillary Lymph Node Specimens in Breast Cancer Patients Treated With Neoadjuvant Systemic Therapy
Authors: Baker Gabrielle M. , King Tari A. , Schnitt Stuart J.
Published: May 2019

Breast and axillary lymph node specimens from breast cancer patients treated with neoadjuvant systemic therapy are being encountered by pathologists with increasing frequency. Evaluation of these specimens presents challenges that differ from those encountered during the examination of other types of breast specimens. This article reviews the key issues regarding the gross and microscopic evaluation of post-neoadjuvant systemic therapy breast and lymph node specimens, and emphasizes the importance of accurate specimen evaluation in assessing treatment response.
The Effect of Asphyxia Arrest Duration on a Pediatric End-Tidal co 2-Guided Chest Compression Delivery Model*
Authors: Hamrick Jennifer L. , Hamrick Justin T. , O’Brien Caitlin E. , Reyes Michael , Santos Polan T. , Heitmiller Sophie E. , Kulikowicz Ewa , Lee Jennifer K. , Kudchadkar Sapna R. , Koehler Raymond C. , Hunt Elizabeth A. , Shaffner Donald H.
Published: May 2019

Objectives:

To determine the effect of the duration of asphyxial arrest on the survival benefit previously seen with end-tidal co
2-guided chest compression delivery.

Design:

Preclinical randomized controlled study.

Setting:

University animal research laboratory.

Subjects:

Two-week-old swine.

Interventions:

After either 17 or 23 minutes of asphyxial arrest, animals were randomized to standard cardiopulmonary resuscitation or end-tidal co
2-guided chest compression delivery. Standard cardiopulmonary resuscitation was optimized by marker, monitor, and verbal feedback about compression rate, depth, and release. End-tidal co
2-guided delivery used adjustments to chest compression rate and depth to maximize end-tidal co
2 level without other feedback. Cardiopulmonary resuscitation for both groups proceeded from 10 minutes of basic life support to 10 minutes of advanced life support or return of spontaneous circulation.

Measurements and Main Results:

After 17 minutes of asphyxial arrest, mean end-tidal co
2 during 10 minutes of cardiopulmonary resuscitation was 18 ± 9 torr in the standard group and 33 ± 15 torr in the end-tidal co
2 group (p = 0.004). The rate of return of spontaneous circulation was three of 14 (21%) in the standard group rate and nine of 14 (64%) in the end-tidal co
2 group (p = 0.05). After a 23-minute asphyxial arrest, neither end-tidal co
2 values (20 vs 26) nor return of spontaneous circulation rate (3/14 vs 1/14) differed between the standard and end-tidal co
2-guided groups.

Conclusions:

Our previously observed survival benefit of end-tidal co
2-guided chest compression delivery after 20 minutes of asphyxial arrest was confirmed after 17 minutes of asphyxial arrest. The poor survival after 23 minutes of asphyxia shows that the benefit of end-tidal co
2-guided chest compression delivery is limited by severe asphyxia duration.
Spinal microglia contribute to cancer-induced pain through system xC −-mediated glutamate release
Authors: Miladinovic Tanya , Singh Gurmit
Published: May 2019

Introduction:

Microglial cells, the resident macrophages of the central nervous system, are a key contributor to the generation and maintenance of cancer-induced pain (CIP). In healthy organisms, activated microglia promote recovery through the release of trophic and anti-inflammatory factors to clear toxins and pathogens and support neuronal survival. Chronically activated microglia, however, release toxic substances, including excess glutamate, causing cytotoxicity. Accordingly, rising attention is given to microglia for their role in abnormal physiology and in mediating neurotoxicity.

Objectives:

To examine the nociceptive relationship between peripherally-released glutamate and microglial xCT.

Methods:

A validated murine model of 4T1 carcinoma cell–induced nociception was used to assess the effect of peripheral tumour on spinal microglial activation and xCT expression. Coculture systems were then used to investigate the direct effect of glutamate released by wildtype and xCT knockdown MDA-MB-231 carcinoma cells on microglial activation, functional system xC
− activity, and protein levels of interferon regulatory factor 8 (IRF8), a transcription factor implicated in microglia-mediated nociception.

Results:

Blockade of system xC
− with sulfasalazine (SSZ) in vivo attenuated nociception in a 4T1 murine model of CIP and attenuates tumour-induced microglial activation in the dorsal horn of the spinal cord. Furthermore, knockdown of xCT in MDA-MB-231 cells mitigated tumour cell–induced microglial activation and functional system xC
− activity in vitro.

Conclusions:

These data collectively demonstrate that the system xCT antiporter is functionally implicated in CIP and may be particularly relevant to pain progression through microglia. Upregulated xCT in chronically activated spinal microglia may be one pathway to central glutamate cytotoxicity. Microglial xCT may therefore be a valuable target for mitigating CIP.