bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of postinjury acute respiratory distress syndrome: Lung injury persists in the era of hemostatic resuscitation
Authors: Kornblith Lucy Z. , Robles Anamaria J. , Conroy Amanda S. , Redick Brittney J. , Howard Benjamin M. , Hendrickson Carolyn M. , Moore Sara , Nelson Mary F. , Moazed Farzad , Callcut Rachael A. , Calfee Carolyn S. , Cohen Mitchell Jay
Published: April 2019

BACKGROUND

Acute respiratory distress syndrome (ARDS) following trauma is historically associated with crystalloid and blood product exposure. Advances in resuscitation have occurred over the last decade, but their impact on ARDS is unknown. We sought to investigate predictors of postinjury ARDS in the era of hemostatic resuscitation.

METHODS

Data were prospectively collected from arrival to 28 days for 914 highest-level trauma activations who required intubation and survived more than 6 hours from 2005 to 2016 at a Level I trauma center. Patients with ratio of partial pressure of oxygen to fraction of inspired oxygen of 300 mmHg or less during the first 8 days were identified. Two blinded expert clinicians adjudicated all chest radiographs for bilateral infiltrates in the first 8 days. Those with left-sided heart failure detected were excluded. Multivariate logistic regression was used to define predictors of ARDS.

RESULTS

Of the 914 intubated patients, 63% had a ratio of partial pressure of oxygen to fraction of inspired oxygen of 300 or less, and 22% developed ARDS; among the ARDS cases, 57% were diagnosed early (in the first 24 hours), and 43% later. Patients with ARDS diagnosed later were more severely injured (ISS 32 vs. 20, p = 0.001), with higher rates of blunt injury (84% vs. 72%, p = 0.008), chest injury (58% vs. 36%, p < 0.001), and traumatic brain injury (72% vs. 48%, p < 0.001) compared with the no ARDS group. In multivariate analysis, head/chest Abbreviated Injury Score scores, crystalloid from 0 to 6 hours, and platelet transfusion from 0 to 6 hours and 7 to 24 hours were independent predictors of ARDS developing after 24 hours.

CONCLUSIONS

Blood and plasma transfusion were not independently associated with ARDS. However, platelet transfusion was a significant independent risk factor. The role of platelets warrants further investigation but may be mechanistically explained by lung injury models of pulmonary platelet sequestration with peripheral thrombocytopenia.

LEVEL OF EVIDENCE

Prognostic study, level IV.
Acute resuscitation with polyethylene glycol-20k: A thromboelastographic analysis
Authors: Wickramaratne Niluka , Kenning Kristine , Reichstetter Heather , Blocher Charles , Li Ru , Aboutanos Michel , Mangino Martin J.
Published: April 2019

BACKGROUND

Previous ex vivo studies have shown that polyethylene glycol-20,000 Da (PEG-20k), a novel synthetic polymer that is highly effective for resuscitation, has a hypocoagulable effect on human blood. This study's objective was to determine the in vivo effects of PEG-20k-based resuscitation solutions on coagulation and platelet function in a porcine model of hemorrhagic shock.

METHODS

Anesthetized pigs underwent controlled hemorrhage until the lactate reached 7 mmol/L or 50% to 55% of their estimated blood volume was removed. A laparotomy was performed to simulate tissue injury. Low volume resuscitation (LVR) was given with fluorescein isothiocyanate-labeled 10% PEG-20k solution (100 mg/mL) or Lactated Ringers, both delivered at volumes equal to 10% of the estimated blood volume (n = 5). Thromboelastography was performed after surgery (baseline), after hemorrhage, and 15 minutes, 120 minutes, and 240 minutes postresuscitation. Hemoglobin was measured to determine changes in plasma volume. Plasma PEG-20k concentration was measured by indicator dilution.

RESULTS

Pigs given PEG-20k survived 2.6-fold longer than controls (p < 0.001) and had a significant increase in plasma volume demonstrated by the sustained drop in hemoglobin, relative to controls. Pigs resuscitated with LR died from hypotension an average of 90 minutes after resuscitation compared to the PEG-20k pigs, which all survived 240 minutes and were then euthanized with normal blood pressure and lactate. Administration of PEG-20k primarily decreased the thromboelastograph maximum amplitude, however this began to return toward baseline by 240 minutes. Peak plasma concentration of PEG-20k after LVR were 40% lower than predicted, based on simple dilution (5.7 mg/mL vs. 10 mg/mL) and the half-life was 59.6 minutes.

CONCLUSION

These data demonstrate that acute resuscitation with PEG-20k significantly improves tolerance to hypovolemia but also decreases platelet function in the coagulation cascade, which was due, in part, to its volume expanding effects.
Quantifying geographic barriers to trauma care: Urban-rural variation in prehospital mortality
Authors: Jarman Molly P. , Hashmi Zain , Zerhouni Yasmin , Udyavar Rhea , Newgard Craig , Salim Ali , Haider Adil H.
Published: April 2019

BACKGROUND

Few studies of trauma care access and quality account for prehospital injury mortality. Little is known about geographic variation in prehospital mortality or the impact of prehospital care on injury disparities.

METHODS

Using the Centers for Disease Control Wide-ranging Online Data for Epidemiologic Research database, we queried county-level incidence of prehospital injury mortality from 1999 to 2016. We linked mortality incidence with county-level urban-rural classifications from the National Center for Health Statistics and population data from the US Census Bureau. We used negative binomial regression to estimate the relationship between rurality and prehospital injury mortality, adjusting for county-level distribution of race, sex, age, income, and insurance coverage. Models were then stratified by injury mechanism (motor vehicle traffic [MVT] vs. penetrating) to determine if prehospital mortality rates varied by type of injury.

RESULTS

Prehospital injury mortality rates were elevated for all urban-rural county classes, relative to large central metro counties, with incidence rate ratios (IRR) ranging from 1.25 (95% confidence interval [CI], 1.16–1.35) for fringe metro counties to 1.69 (95% CI, 1.58–1.82) for noncore counties. For MVT injury, IRRs for urban-rural classes compared with large central metro counties ranged from 2.02 (95% CI, 1.85–2.21) for fringe metro counties to 3.02 (95% CI, 2.76–3.30) to noncore counties. Incidence of prehospital mortality from penetrating injury was 14% higher for noncore counties compared to large central metro counties (IRR, 1.14; 95% CI, 1.05–1.23).

CONCLUSION

There is substantial geographic variation in prehospital injury mortality in the United States, with risk of prehospital death increasing with rurality. Patterns of prehospital death associated with penetrating and MVT injuries suggest that improvements to both trauma center access, prehospital care, and primary injury prevention are essential to reduce preventable injury deaths.

LEVEL OF EVIDENCE

Retrospective ecological analysis, level III.
Hypobaria during aeromedical evacuation exacerbates histopathological injury and modifies inflammatory response in rats exposed to blast overpressure injury
Authors: Dayani Yaron , Stierwalt Joshua , White Andrea , Chen Ye , Arnaud Francoise , Jefferson Michelle A. , Goforth Carl , Malone Debra , Scultetus Anke H.
Published: April 2019

BACKGROUND

Aeromedical evacuation (AE) is often used as a rapid and effective way to evacuate patients. However, little is known about the possible effects of AE on patients with blast and traumatic brain injury. In the current study, we used blast overpressure (BOP) as a method to introduce traumatic brain injury in rats and investigated the effects of hypobaria during AE on histology and inflammatory response.

METHODS

Animals were exposed to a 12-hour flight 2 days after BOP and euthanized 48 hours after flight. Control animals were kept at normobaria.

RESULTS

Overall, BOP animals exposed to flight demonstrated higher histopathologic injury scores as compared to control animals in lungs, brain, kidney, heart, and intestine. The BOP animals exposed to normobaria exhibited a proinflammatory response compared to those that were not blasted, an observation that was not seen in BOP animals exposed to hypobaria.

CONCLUSION

These data suggest that AE 48 hours post blast may lead to impairment in the inflammatory process and worsening of long-term outcomes.

LEVEL OF EVIDENCE

Animal research, level II.
Cold-stored whole blood platelet function is preserved in injured children with hemorrhagic shock
Authors: Leeper Christine M. , Yazer Mark H. , Cladis Franklyn P. , Saladino Richard , Triulzi Darrell J. , Gaines Barbara A.
Published: April 2019

BACKGROUND

Recent data demonstrate the safety of uncrossmatched cold-stored whole blood (WB) transfusion in pediatric trauma patients. The hemostatic capabilities of platelets within the cold-stored WB unit have been demonstrated via in vitro studies and animal models. However, platelet function has not been evaluated in pediatric recipients of cold-stored WB transfusions.

METHODS

Injured children, 2 years or older and 10 kg or greater with hemorrhagic shock received up to 30 mL/kg of cold-stored, low titer (<50) anti-A and -B, leukoreduced, group O- WB during their initial resuscitation. Patients were included if (1) they received WB and no conventional platelets, and (2) platelet count and thromboelastography maximum amplitude were measured both before and after transfusion. These data and relevant clinical outcomes (mortality, intensive care unit length of stay [LOS], hospital LOS and ventilator days) were compared to a historical cohort of pediatric trauma patients who received uncrossmatched red blood cells (RBC) and conventional room temperature platelets.

RESULTS

Twenty-two children were included in the study; 14 in the component cohort versus 8 in the WB cohort. Neither posttransfusion platelet count (129 × 109/L vs. 135 × 109/L) nor function (thromboelastography maximum amplitude, 59.5 mm vs. 60.2 mm) differed significantly between children receiving cold-stored platelets within the WB unit versus children who received conventional warm platelets. Median (interquartile range) weight-adjusted platelet transfusion volume in the historical cohort was 4.6 (2.5–7.7) mL/kg vs. 2.4 (1.3–4.0) mL/kg in the WB cohort (p = 0.03). There was no difference between groups in age, race, mechanism of injury, Injury Severity Score, vital signs, and severe traumatic brain injury (TBI). Outcomes, including mortality, intensive care unit LOS, hospital LOS, and ventilator days, were not significantly different between groups.

CONCLUSION

No difference was seen in posttransfusion platelet number or function in severely injured children receiving cold-stored WB platelets as compared to those receiving conventional room temperature-stored platelets. Larger cohorts are required to confirm these findings.

LEVEL OF EVIDENCE

Therapeutic, level IV.
The Effect of Ceramic Painting on the Life Satisfaction and Cognitive Status of Older Adults Residing in a Nursing Home
Authors: Çetinkaya Funda , Duru Aşiret Güler , Direk Filiz , Özkanlı Nilüfer Nazende
Published: April 2019

Objectives:

The aim of this experimental study was to assess the cognitive activity and satisfaction with life of older adults in nursing home before and after ceramic painting.

Methods:

The sample of the survey consisted of 15 older adults each in the intervention and control groups. Data for the study were collected using a questionnaire form developed to determine the sociodemographic characteristics of the older adults, the Mini-Mental State Examination, and the Life Satisfaction Scale.

Results:

There was a statistically significant increase in the mean Mini-Mental State Examination score of the intervention group compared with the control group at the end of ceramic painting (P < .05). The intervention group had increased average Life Satisfaction Scale scores in the posttest compared with the control group, although the difference was not statistically significant.

Conclusions:

The results showed that art therapy with ceramic painting was a positive effect on the cognitive levels and quality of life of older adults.
The Dual-Tasking Overload on Functional Mobility Is Related to Specific Cognitive Domains in Different Subtypes of Parkinson's Disease
Authors: Pereira Marcelo Pinto , Batistela Rosangela Alice , Rocha dos Santos Paulo Cezar , Simieli Lucas , Gobbi Lilian Teresa Bucken
Published: April 2019

Objective:

To investigate the role of different cognitive domains on the dual-tasking overload during functional mobility in Parkinson's disease subtypes.

Methods:

Eleven tremor-dominant and 15 akinetic-rigid participants performed the Timed Up-and-Go (TUG) test with and without a secondary task; executive function and attention were assessed.

Results:

Dual tasking increased TUG time in both groups (tremor-dominant: 6.38 ± 1.19 seconds and 7.79 ± 1.48 seconds; akinetic-rigid: 8.80 ± 3.09 seconds and 10.38 ± 3.77 seconds). Dual-tasking overload was correlated with attention in akinetic-rigid and mental inflexibility in tremor-dominant participants. Cognitive scores were similar between groups.

Conclusion:

Distinguished cognitive domains are involved with dual-tasking overload in Parkinson's disease subgroups.
Effect of Insoles With a Toe-Grip Bar on Toe-Grip Strength and Body Sway in Middle-Aged and Elderly Women
Authors: Nakano Hideki , Murata Shin , Abiko Teppei , Sakamoto Masashi , Matsuo Dai , Kawaguchi Michio , Sugo Youji , Matsui Hiroaki
Published: April 2019

The effects of insoles with a toe-grip bar on toe-grip strength (TGS) and body sway in middle-aged and elderly women were investigated. Twelve middle-aged and elderly women wore shoes with insoles with a toe-grip bar. TGS and the total length of the center of pressure sway in the 1- and 2-leg stances (OLS-TL and TLS-TL) were measured before (Pre1) and after (Pre2) the baseline phase and after the intervention phase (Post). TGS, OLS-TL and TLS-TL significantly improved in the Post condition compared with the Pre1 and Pre2 conditions. The results of this study suggest that insoles with a toe-grip bar can improve TGS and body sway in middle-aged and elderly women.
The Effects of Abdominal Massage in the Management of Constipation in Elderly People
Authors: Baran Ayşe , Ateş Sebahat
Published: April 2019

Objective:

This study was conducted to evaluate the efficacy of abdominal massage in the management of age-related constipation.

Subject and Methods:

Thirty participant control groups and 30 other participants constituted the treatment group. When the abdominal massage was applied to the treatment group for 15 minutes for 4 weeks, it was not applied to the control group.

Results:

As a result of applying abdominal massage for 4 weeks, both groups had a significant increase in the diagnostic criteria of Rome III. According to Bristol Stool Scale, the constipation problems were improved in the treatment group.

Conclusions:

Abdominal massage has been found as an effective method for the management of constipation commonly seen in the elderly.
Building Legitimacy by Valuing the Expert Opinion in the Conservative Treatment of Thumb Carpometacarpal Joint Osteoarthritis
Authors: Cantero-Téllez Raquel , Valdes Kristin , O'Brien Virgina , Berjano Pedro , Pedersini Paolo , Villafañe Jorge Hugo
Published: April 2019

Background:

This article describes and provide information regarding the expert opinion on the conservative treatment of thumb carpometacarpal (CMC) joint osteoarthritis (OA). The aim of this study was to elucidate expert opinion on the conservative treatment of thumb CMC joint OA.

Methods:

A 21-item survey to determine the practice patterns of international hand researchers who treat arthritis of the CMC joint was developed and distributed through a professional online survey service to ensure confidentiality and anonymity.

Results:

All experts assessed the intensity of pain in CMC joint OA, and the visual analog scale was the method that was most frequently used by 87.5% of respondents.

Conclusions:

This survey provides valuable data regarding current practice patterns by valuing the expert opinion on the conservative treatment of thumb CMC joint OA.
A Survey of Emergency Department Quality Improvement Activities
Authors: Pink Edward , Ding Mingshuang , Murdoch Ian , Tan Victoria Ie Ching
Published: April 2019

This article describes the quality improvement process used to implement a waiting area within fast track. Staff and patient survey data indicated a significant decrease in workload, with a subsequent high satisfaction of both groups following the redesign process.
Staphylococcal Scalded Skin Syndrome
Authors: Jordan Kathleen S.
Published: April 2019

Staphylococcal scalded skin syndrome (SSSS) is a major exfoliating skin infection primarily seen in neonates and young children that can lead to serious morbidity. Although this condition is not commonly encountered, evidence indicates that the incidence and prevalence of this infection is increasing. It is essential that emergency care providers are knowledgeable regarding the differential diagnosis and clinical-decision making process for accurate and timely diagnosis and treatment. This case study highlights the challenges faced in the emergency department in the diagnosis and management of SSSS, including pathophysiology, epidemiology, differential diagnosis and medical management.
Sex Trafficking
Authors: Reap Valerie J.
Published: April 2019

As the ever-increasing demands of health care evolve in their complexities, so too shall the role of health care providers. In 2016, the International Labour Organization announced that there were approximately 40.3 million victims of human trafficking worldwide, with 4.8 million enslaved in sexual exploitation and 15.4 million in forced marriages (International Labour Organization, 2016). Human trafficking has rapidly proliferated in recent years and is now considered the second most lucrative criminal activity in the world, with sex trafficking accounting for approximately 80 percent of this industry (UNODC, 2009). Recent data from the National Center for Missing and Exploited Children (2017) estimates that one out of every seven runaways reported in 2017 was likely a victim of child sex trafficking, with the average age of victimization being fifteen years of age. According to A. Egyud, K. Stephens, B. Swanson-Bierman, M. DiCuccio, and K. Whiteman (2017), an estimated 100,000 to 300,000 youths are at risk for sex trafficking annually within the United States alone. Sadly, Egyud et al. (2017) found that approximately 87 percent of sex trafficking victims had sought care during their captivity, predominantly in emergency departments. This data has been corroborated by several other researchers, prompting proposals for the introduction of human trafficking education among emergency medicine providers. The concept and operational definition of sex trafficking however remains ambiguous and unclear, with some apparent variation among professions. This article is intended to provide clarification on the concept distinctly specific to victims of sex trafficking.
The Use of Ketamine for the Management of Acute Pain in the Emergency Department
Authors: Davis Wesley D. , Davis Kristina A. , Hooper Katie
Published: April 2019

Ketamine has been used as an anesthetic agent for over 50 years. At the upper end of the dosing range, it displays dissociative anesthetic and amnestic effects, while at lower doses, it acts as an analgesic and demonstrates opioid-sparing capabilities. Ketamine is unique in its preservation of hemodynamic stability and respiratory function, and is used extensively in the emergency department (ED) for procedural sedation and the facilitation of brief painful procedures. Despite evidence supporting its safety and efficacy as an analgesic agent at sub-dissociative doses, its use in the ED for the management of acute pain remains uncommon. New guidelines were published in July 2018 by the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists that provide a framework for identifying patients who are likely to benefit from the use of Ketamine in an acute pain setting.
Relationship Between Changes in Prehospital Blood Pressure and Early Neurological Deterioration in Spontaneous Intracerebral Hemorrhage
Authors: Tsou Yu-Ju , Lan Kai-Ping , Fan Ju-Sing
Published: April 2019

The aim of this study was to explore the relationship between changes in prehospital blood pressure (BP) and the incidence of early neurological deterioration (END) after spontaneous intracerebral hemorrhage (SICH) in patients who arrive at the emergency department (ED) with a normal Glasgow Coma Scale (GCS) score. Records of consecutive adults with SICH transported by ambulance and treated in our ED from January 2015 to December 2017 were retrospectively reviewed. The study cohort included all patients with SICH occurring within the previous 6 hr who had a normal GCS score on ED arrival. Detailed information was retrieved from our hospital's intracerebral hemorrhage databank and then cross-checked in the medical and nursing charts to confirm completeness and accuracy. Early neurological deterioration was defined as a decrease of 2 or more points in the GCS score within 6 hr after ED arrival. The change in prehospital BP was defined as the BP on ED arrival minus the initial on-scene BP. An association between a change in prehospital BP and the occurrence of END was assessed by univariate and multivariate analyses (multiple logistic regression analysis). Of the 168 patients evaluated, 36 (21.4%) developed END. Factors associated with END on univariate analysis were regular antiplatelet agent use, shorter elapsed time, on-scene systolic blood pressure (SBP), prehospital SBP increase of 15 mmHg or more, intraventricular extension of the hematoma, and the presence of 3 or more noncontrast computed tomographic signs of hematoma expansion. After adjusting for other covariates, an increase in prehospital SBP of 15 mmHg or more was significantly associated with a higher risk of END. In patients with SICH who arrive at the ED with a normal GCS score, an increase in the prehospital SBP of more than 15 mmHg is associated with a higher incidence of END.
Evaluation of Traumatic Uveitis in the Emergency Department
Authors: Pinch Colleen M.
Published: April 2019

Eye trauma is a common presenting complaint in the emergency department. Correctly identifying the underlying pathology in eye trauma is critical to developing appropriate treatment plans that reduce the risk of long-term sequelae, and reduce or eliminate threats to vision. The clinical evaluation and diagnosis can be complex, and the presentation of serious eye conditions can be similar to that of more benign conditions. This article focuses on traumatic uveitis. It addresses the elements of history and examination that should suggest uveitis as the cause of pain and redness following trauma to the eye. It also outlines specific findings that can help differentiate uveitis from other causes of eye pain and redness following trauma. Included is a brief description of the pathophysiology of uveitis and the mechanism by which this inflammatory condition can result in loss of vision. Discussion includes recommended treatment. It offers a straightforward approach to making the diagnosis of traumatic uveitis.
Efficacy and Safety of Empagliflozin in the Management of Diabetes Mellitus in Heart Transplant Recipients
Authors: Cehic Matthew G. , Muir Christopher A. , Greenfield Jerry R. , Hayward Christopher , Jabbour Andrew , Keogh Anne , Kotlyar Eugene , Muthiah Kavitha , Macdonald Peter S.
Published: April 2019

Background.

Type 2 diabetes mellitus (T2DM) is prevalent in patients undergoing heart transplant, and in those without preexisting T2DM, posttransplant diabetes mellitus may develop. Both T2DM and posttransplant diabetes mellitus have been associated with increased morbidity and mortality following heart transplantation. Empagliflozin is an effective glucose-lowering therapy that reduces the incidence of major cardiovascular events in patients with T2DM. The safety and efficacy of empagliflozin in transplant patients with diabetes mellitus has yet to be established.

Methods.

Clinical outcomes were retrospectively examined in 22 heart transplant recipients treated with empagliflozin and compared with those of 79 heart transplant patients with diabetes mellitus receiving alternative glucose-lowering therapies.

Results.

Three adverse events were recorded in empagliflozin-treated patients, leading to treatment discontinuation in 1. There were no genitourinary infections. Treatment with empagliflozin for 12 months was associated with reductions in weight, body mass index, glycated hemoglobin, and frusemide dose that were not seen in the control group. There were no large changes observed in blood pressure (systolic or diastolic) or renal function (serum urea, creatinine, or estimated glomerular filtration rate) after 12 months of treatment with empagliflozin or alternative glucose-lowering therapies.

Conclusions.

Empagliflozin appears safe and effective in the management of selected patients with diabetes mellitus following heart transplantation.
Survival Outcomes Are Not Affected When Liver Transplant Surgery Is Done at Night, During Weekends, or Summer Months
Authors: Thuluvath Paul J. , Amjad Waseem , Savva Yulia , Thuluvath Avesh J. , LaMattina John
Published: April 2019

Background.

It has been suggested that hospitalized patients may get suboptimal care in nights or on weekends or summer holidays due to sleep deprivation, physician fatigue, or reduced medical staffing. Our objective was to determine whether there were differences in outcomes when surgery was performed in the night (10 pm–6 am), on weekends (Saturday or Sunday), or during summer months (June–August).

Methods.

We used United Network for Organ Sharing (UNOS) data sets of adults transplanted between February 27, 2002, and September 30, 2016. We estimated the start time of liver transplant surgery by utilizing the cross-clamp time and cold ischemia time (cross-clamp time + cold ischemia time – 2 h). The survival outcomes were estimated by Kaplan-Meier survival analysis. Patients with hepatocellular carcinoma (HCC) were analyzed separately. The independent effect of time of transplant on outcomes was analyzed after adjusting for common confounders, including Model for End-stage Liver Diseases scores and transplant center volume.

Results.

During the study period, 4 434 (9.6%) were done in the night, 12 147 (26.4%) over weekends, and 11 976 (26%) during summer months. The graft and patient survival and complications were not influenced by the time of transplant for both HCC and non-HCC population. Cox regression analysis after adjusting for risk factors, including Model for End-stage Liver Diseases, donor risk index, and liver center volume, confirmed that there were no significant differences in outcomes.

Conclusions.

Our study showed that the time of transplant surgery whether done during nights, weekends, or summer months had no effect on graft or patient survival irrespective of center volume, patient, or donor risk factors.
A ride in the park: Cycling in different outdoor environments modulates the auditory evoked potentials
Authors: Scanlon Joanna E. M. , Redman Eden X. , Kuziek Jonathan W. P. , Mathewson Kyle E.
Published: April 2019

In this study, we investigated the effect of environmental sounds on ERPs during an auditory task, by having participants perform the same dual task in two different outdoor environments. Participants performed an auditory oddball task while cycling outside both in a quiet park and near a noisy roadway. While biking near the roadway, an increased N1 amplitude was observed when evoked by both standard and target tones. This may be due to attentional processes of enhancing sound processing in the noisier environment. No behavioural differences were found. Future directions include investigating auditory ERPs in more realistic studies outside of laboratory.
Google searches accurately forecast RSV hospitalizations
Authors: Althouse Benjamin M , Weinberger Daniel M , Scarpino Samuel V , Pitzer Virginia E , Ayers John W , Wenger Edward , Fung Isaac Chun-Hai , Dredze Mark , Hu Hao
Published: April 2019

Background

Hospitalization of children with respiratory syncytial virus (RSV) is common and costly. Traditional sources of hospitalization data, useful for public health decision-makers and physicians to make decisions, are themselves costly to acquire and are subject to delays from gathering to publication. Here we use Google searches for RSV as a proxy for RSV hospitalizations.

Methods

Searches for “RSV” and numbers of RSV hospitalizations in WA, MD, FL, and CT were examined from 2004–2018. Running correlation coefficients and phase angles between search and hospitalizations were calculated. Various machine learning models were compared to assess the ability of searches to forecast hospitalizations. Using search data from all 50 US states, we use K-means clustering to identify RSV transmission clusters. We calculate the timing of the optimal timing of RSV prophylaxis initiation as the week beginning the 24-week period covering 95% of all RSV cases.

Results

High correlations (> 0.95) and low phase differences were seen between counts of hospitalizations and search volume in WA, MD, FL, and CT. Searching for RSV began in FL and radiated outward and three distinct transmission clusters were identified: the south and northeast, the northwest and Appalachia, and the center of the country. Calculated initiation dates for prophylaxis closely followed those calculated using traditional data sources (correlation = 0.84).

Conclusions

This work validates searches as a proxy for RSV hospitalizations. Search query surveillance of RSV is a rapid and no-cost addition to traditional RSV hospitalization surveillance and may be useful for medical and public health decision-making.
A microfabricated, 3D-sharpened silicon shuttle for insertion of flexible electrode arrays through dura mater into brain
Authors: Joo Hannah R. , Lan Fan Jiang , Chen Supin , Pebbles Jeanine A. , Liang Hexin , Chung Jason E. , Yorita Allison M. , Tooker Angela C. , Tolosa Vanessa M. , Geaghan-Breiner Charlotte , Roumis Demetris K. , Liu Daniel F. , Haque Razi , Frank Loren M.
Published: April 2019

Electrode arrays for chronic implantation in the brain are a critical technology in both neuroscience and medicine. Recently, flexible, thin-film polymer electrode arrays have shown promise in facilitating stable, single-unit recordings spanning months in rats. While array flexibility enhances integration with neural tissue, it also requires removal of the dura mater, the tough membrane surrounding the brain, and temporary bracing to penetrate the brain parenchyma. Durotomy increases brain swelling, vascular damage, and surgical time. Insertion using a bracing shuttle results in additional vascular damage and brain compression, which increase with device diameter; while a higher-diameter shuttle will have a higher critical load and more likely penetrate dura, it will damage more brain parenchyma and vasculature. One way to penetrate the intact dura and limit tissue compression without increasing shuttle diameter is to reduce the force required for insertion by sharpening the shuttle tip. We describe a novel design and fabrication process to create silicon insertion shuttles that are sharp in three dimensions and can penetrate rat dura, for faster, easier, and less damaging implantation of polymer arrays. Sharpened profiles are obtained by reflowing patterned photoresist, then transferring its sloped profile to silicon with dry etches. We demonstrate that sharpened shuttles can reliably implant polymer probes through dura to yield high quality single unit and local field potential recordings for at least 95 days. On insertion directly through dura, tissue compression is minimal. This is the first demonstration of a rat dural-penetrating array for chronic recording. This device obviates the need for a durotomy, reducing surgical time and risk of damage to the blood-brain barrier. This is an improvement to state-of-the-art flexible polymer electrode arrays that facilitates their implantation, particularly in multi-site recording experiments. This sharpening process can also be integrated into silicon electrode array fabrication.
Machine learning predicts early-onset acute organ failure in critically ill patients with sickle cell disease
Authors: Mohammed Akram , Podila Pradeep S. B. , Davis Robert L. , Ataga Kenneth I. , Hankins Jane S. , Kamaleswaran Rishikesan
Published: April 2019

Background

Sickle cell disease (SCD) is a genetic disorder of the red blood cells, resulting in multiple acute and chronic complications including pain episodes, stroke, and kidney disease. Patients with SCD develop chronic organ dysfunction, which may progress to organ failure during disease exacerbations. Early detection of acute physiological deterioration leading to organ failure is not always attainable. Machine learning techniques that allow for prediction of organ failure may enable earlier identification and treatment, and potentially reduce mortality. We tested the hypothesis that machine learning physiomarkers could predict the development of organ dysfunction in an adult sample of patients with SCD admitted to intensive care units.

Methods and Findings

We studied 63 sequential SCD patients with 163 patient encounters, mean age 33.0±11.0 years, admitted to intensive care units, some of whom (6.7%) had pre-existing cardiovascular or kidney disease. A subset of these patient encounters (37; 23%) met sequential organ failure assessment (SOFA) criteria. The site of organ failure included: central nervous system (32), cardiovascular (11), renal (10), liver (7), respiratory (5) and coagulation (2) systems. Most (81.5%) of the patient encounters who experienced organ failure had single organ failure. The other 126 SCD patient encounters served as controls. A set of signal processing features (such as fast fourier transform, energy, continuous wavelet transform, etc.) derived from heart rate, blood pressure, and respiratory rate were identified to distinguish patients with SCD who developed acute physiological deterioration leading to organ failure, from SCD patients who did not meet the criteria. A random forest model accurately predicted organ failure up to six hours prior to onset, with a five-fold cross-validation accuracy of 94.57% (average sensitivity and specificity of 90.24% and 98.9% respectively).

Conclusions

This study demonstrates the viability of using machine learning to predict acute physiological deterioration heralded organ failure among hospitalized adults with SCD. The discovery of salient physiomarkers through machine learning techniques has the potential to further accelerate the development and implementation of innovative care delivery protocols and strategies for medically vulnerable patients.
Neurocognitive mechanisms of d-cycloserine augmented single-session exposure therapy for anxiety
Authors: Reinecke Andrea , Nickless Alecia , Browning Michael , Harmer Catherine J.
Published: April 2019

Objective

Drugs targeting the N-Methyl-D-aspartic acid (NMDA) system and the ability to learn new associations have been proposed as potential adjunct treatments to boost the success of exposure therapy for anxiety disorders. However, the effects of the NMDA partial agonist d-cycloserine on psychological treatment have been mixed. We investigated potential neurocognitive mechanisms underlying the clinical effects of d-cycloserine-augmented exposure, to inform the optimal combination of this and similar agents with psychological treatment.

Methods

Unmedicated patients with panic disorder were randomised to single-dose d-cycloserine (250mg; N=17) or matching placebo (N=16) 2hrs before one session of exposure therapy. Neurocognitive markers were assessed one day after treatment, including reaction-time based threat bias for fearful faces and amygdala response to threat. Clinical symptom severity was measured using self-report and clinician-rated scales the day before and after treatment, and at 1- and 6-months follow-up. Analysis was by intention-to-treat.

Results

One day after treatment, threat bias for fearful faces and amygdala threat response were attenuated in the drug compared to the placebo group. Lower amygdala magnitude predicted greater clinical improvement during follow-up across groups. D-cycloserine led to greater clinical recovery at 1-month follow-up (d-cycloserine 71% versus placebo 25%).

Discussion

D-cycloserine-augmented single-session exposure therapy reduces amygdala threat response, and this effect predicts later clinical response. These findings highlight a neurocognitive mechanism by which d-cycloserine may exert its augmentative effects on psychological treatment and bring forward a marker that may help understand and facilitate future development of adjunct treatments with CBT for anxiety disorders. (D-cycloserine Augmented CBT for Panic Disorder; clinicaltrials.gov;NCT01680107)
Parasitoid community responds indiscriminately to fluctuating spruce budworm and other caterpillars on balsam fir
Authors: Greyson-Gaito Christopher J. , McCann Kevin S. , Fründ Jochen , Lucarotti Christopher J. , Smith M. Alex , Eveleigh Eldon S.
Published: April 2019

The world is astoundingly variable, and individuals to whole communities must respond to variability to survive. One example of nature’s variability is the massive fluctuations in spruce budworm (Choristoneura fumiferanaClemens, Lepidoptera: Tortricidae) populations that occur over 35 years. We examined how the parasitoid community altered its parasitism of budworm and other caterpillar species in response to these fluctuations. Budworm and other caterpillar species were sampled from balsam fir in three plots for 14 years in Atlantic Canada, and then reared to identify any emerging parasitoids. We found that the parasitoid community showed a simple linear, indiscriminate response (i.e., no preference, where densities purely dictated parasitism rates) to changes in budworm densities relative to other caterpillar species on balsam fir. We also observed strong changes in topology and distributions of interaction strengths between the parasitoids, budworm and other caterpillar species as budworm densities fluctuated. Our study contributes to the suggestion that hardwood trees are a critical part of the budworm-parasitoid food web, where parasitoids attack other caterpillar species on hardwood trees when budworm populations are low. Taken together, our study shows that a parasitoid community collectively alters species interactions in response to variable budworm densities, fundamentally shifting food web pathways.
The impact of geographic targeting of oral cholera vaccination in sub-Saharan Africa: a modeling study
Authors: Lee Elizabeth C. , Azman Andrew S. , Kaminsky Joshua , Moore Sean M. , McKay Heather S. , Lessler Justin
Published: April 2019

Background

In May 2018, the World Health Assembly committed to reducing worldwide cholera deaths by 90% by 2030. Oral cholera vaccine (OCV) plays a key role in reducing the near-term risk of cholera, although global supplies are limited. Characterizing the potential impact and cost-effectiveness of mass OCV deployment strategies is critical for setting expectations and developing cholera control plans that maximize chances of success.

Methods and Findings

We compared the projected impacts of vaccination campaigns across sub-Saharan Africa from 2018 through 2030 when targeting geographically according to historical cholera burden and risk factors. We assessed the number of averted cases, deaths, disability-adjusted life-years, and cost-effectiveness with models that account for direct and indirect vaccine effects and population projections over time. Under current vaccine supply projections, an approach optimized to targeting by historical burden is projected to avert 828,971 (95% CI: 803,370-859,980) cases (equivalent to 34.0% of projected cases; 95% CI: 33.2-34.8). An approach that balances logistical feasibility with targeting historical burden is projected to avert 617,424 (95% CI: 599,150-643,891) cases. In contrast, approaches optimized for targeting locations with limited access to water and sanitation are projected to avert 273,939 (95% CI: 270,319-277,002) and 109,817 (95% CI: 103,735-114,110) cases, respectively. We find that the most logistically feasible targeting strategy costs $1,843 (95% CI: 1,328-14,312) per DALY averted during this period and that effective geographic targeting of OCV campaigns can have a greater impact on cost-effectiveness than improvements to vaccine efficacy and moderate increases in coverage. Although our modeling approach did not project annual changes in baseline cholera risk or incorporate immunity from natural cholera infection, our estimates of the relative performance of different vaccination strategies should be robust to these factors.

Conclusions

Our study suggests that geographic targeting is critical to the cost-effectiveness and impact of oral cholera vaccination campaigns. Districts with the poorest access to improved water and sanitation are not the same as districts with the greatest historical cholera incidence. While OCV campaigns can improve cholera control in the near-term, without rapid progress in developing water and sanitation services, our results suggest that vaccine use alone are unlikely to allow us to achieve the 2030 goals.
Maize Kernel Development Stage the Primary Factor in Differential Gene Expression in Response to Two Methods of Field Inoculation withAspergillus flavus
Authors: Wahl Nancy J. , Murray Seth C. , Zhang Hong-Bin , Zhang Meiping , Dickens C. Michael , Isakeit Thomas S.
Published: April 2019

Background

Aflatoxins, produced by the fungusAspergillus flavus, often contaminate preharvest maize (Zea maysL.) grain under heat and drought stresses, posing serious health hazards to humans and livestock, and resulting in significant costs to identify and dispose of contaminated grain. This study was designed to investigate the changes in differential gene expression during seed morphogenesis and maturation in the “aflatoxin resistant” Argentinian inbred line Tx772 when challenged by the introduction ofA. flavusthrough two different methods of ear inoculation; non-wounding (silk channel, used to select Tx772), wounding (side needle) and a non-inoculated control.

Method and Findings

Grain maturity had the largest effect on overall RNA-Seq differential gene expression (DGE) as measured by edgeR of the Bioconductor platform. However, within each stage of development, ranging from blister to dent, similar up-regulation in expression of many maize genes following inoculation with either method was observed; a total of 16 genes previously associated with resistance to pathogens were identified among the transcripts differentially expressed (DE) at p ≤ .05, FDR ≤ .10, and fold change ≥ 2.0 over all stages. The side needle technique produced a larger effect of infection as evidenced by 6,324 fungal reads versus 518 in silk channel and a higher level of aflatoxin. Correlations between approximately 7,000 fungal reads and the number of maize DE genes for each of the eight treatment groups was 0.56 (p = .152) and was 0.65 (p < .001) with levels of aflatoxin ranging from 0 to 137 ng g-1.

Conclusion

These correlations provided an internal measure of effectiveness of inoculation methods that were associated with the mostly up-regulation of defense-related genes in response to the presence ofAspergillus flavusin a unique maize genetic background.
Genetic modification of primary human B cells generates translationally-relevant models of high-grade lymphoma
Authors: Caeser Rebecca , Di Re Miriam , Krupka Joanna A , Gao Jie , Lara-Chica Maribel , Dias João M.L , Cooke Susanna L , Fenner Rachel , Usheva Zelvera , Runge Hendrik , Beer Philip A , Eldaly Hesham , Pak Hyo-Kyung , Park Chan-Sik , Vassiliou George , Huntly Brian J.P , Mupo Annalisa , Bashford-Rogers Rachael JM , Hodson Daniel J
Published: April 2019

Sequencing studies of Diffuse Large B Cell Lymphoma (DLBCL) have identified hundreds of recurrently altered genes. However, it remains largely unknown whether and how these mutations may contribute to lymphomagenesis, either individually or in combination. Existing strategies to address this problem predominantly utilize cell lines, which are limited by their initial characteristics and subsequent adaptions to prolongedin vitroculture. Here, we describe a novel co-culture system that enables theex vivoexpansion and viral transduction of primary human germinal center B cells. The incorporation of CRISPR/Cas9 technology enables high-throughput functional interrogation of genes recurrently mutated in DLBCL. Using a backbone ofBCL2with eitherBCL6orMYCwe have identified co-operating oncogenes that promote growth and survival, or even full transformation into synthetically engineered models of DLBCL. The resulting tumors can be expanded and sequentially transplantedin vivo, providing a scalable platform to test putative cancer genes and for the creation of mutation-directed, bespoke lymphoma models.
Immunogenomic landscape of hematological malignancies
Authors: Dufva Olli , Pölönen Petri , Brück Oscar , Keränen Mikko , Mehtonen Juha , Kumar Ashwini , Heckman Caroline , Siitonen Sanna , Granberg Kirsi , Leivonen Suvi-Katri , Meriranta Leo , Leppä Sirpa , Nykter Matti , Lohi Olli , Heinäniemi Merja , Mustjoki Satu
Published: April 2019

Understanding factors that shape the immune landscape across hematological malignancies is essential for immunotherapy development. Here, we integrated over 8,000 transcriptomes and over 1,000 samples with multilevel genomic data of hematological cancers to investigate how immunological features are linked to cancer subtypes, genetic and epigenetic alterations, and patient survival. Infiltration of cytotoxic immune cells was associated with distinct microenvironmental responses and driver alterations in different cancers, such asTP53in acute myeloid leukemia andDTX1in diffuse large B cell lymphoma. Epigenetic modification ofCIITAregulating antigen presentation, cancer type-specific immune checkpoints such as VISTA in myeloid malignancies, and variation in cancer antigen expression further contributed to immune heterogeneity. Prognostic models highlighted the significance of immunological properties in predicting survival. Our study represents the most comprehensive effort to date to link immunology with cancer subtypes and genomics in hematological malignancies, providing a resource to guide future studies and immunotherapy development.