bluuebunny/crossref_metadata_2025 huggingface dataset:
Patch Testing Tools of the Trade
Authors: Lampel Heather P. , Atwater Amber Reck
Published: June 2016

Epicutaneous patch testing is the gold standard for obtaining a diagnosis of allergic contact dermatitis. Patients with allergic contact dermatitis who are undergoing patch testing may be taking or using topical, oral, or injectable immunosuppressant medications. Herein, we elucidate guidelines for the use of antihistamines and topical systemic immunosuppressants during the patch test process.
Bleach Baths
Authors: A. McGowan Maria , Jacob Sharon E.
Published: June 2016

Nursing care and patient education are integral to compliance with dermatologic medical treatments. This column has been developed in partnership with the caring nurses dedicated to optimizing patient care through practicum-based education and treatment. This printable focuses on bleach baths for eczema.
Adalimumab
Authors: Brankov Nikoleta , Jacob Sharon E.
Published: June 2016

A drug is a particular substance in physiology that exerts an effect when ingested or otherwise introduced into the body. Drugs may be administered in a variety of constitutions from capsules, injections, creams, and ointments to inhalants, liquids, and dermal patches. Administration is by way of different routes, namely, topical, parenteral, inhalation, and via injection routes such as subcutaneous, intramuscular, or intravenous. The purpose of this column is to direct the reader’s attention to some of the more common drugs used in dermatology. The mechanism of action for the drug, the indications for its use, efficacy, dosing and administration, monitoring guidelines, adverse side effects, and any standard alternatives are discussed. In addition, this column contains pertinent patient education on the use of the medication. This article focuses on a common medication for plaque psoriasis, adalimumab.
Role of Transbronchial Needle Core Biopsy in the Diagnosis of Mediastinal Diseases
Authors: Galluccio Giovanni , Palazzolo Manuela , Battistoni Paolo , Dello Iacono Raffaele , Batzella Sandro , Caterino Umberto , Lucantoni Gabriele
Published: June 2016

Background:

Enlarged lymph nodes or mediastinal masses diagnosed by computed tomographic scan before the advent of bronchoscopic procedures (TBNA or EBUS) were usually investigated using a thoracic surgical approach. In this paper, we report the experience with the use of a modified rigid tru-cut needle in the bioptical approach to mediastinal masses; to determine whether it could be considered a valid alternative to surgery, we investigated the diagnostic accuracy of this new endoscopic technique.

Methods:

A total of 156 selected patients with radiographic evidence of lymphadenopathy or mediastinal masses (subcarinal and paratracheal with a short-axis diameter >3 cm) were studied in our center by rigid bronchoscopy using a 18-G tru-cut needle to obtain a core biopsy of the lesion.

Results:

In 140 of 156 cases (89.7%), a histologically correct diagnosis was reached without perioperative or postoperative complications. A total of 114 (81.4%) malignant and 26 (18.6%) benign lesions were diagnosed avoiding further invasive surgical approach.

Conclusions:

Our results confirm that, in selected cases, transbronchial rigid core biopsy could be considered a safe and valid alternative technique to more invasive surgical approach in the diagnosis of mediastinal diseases.
Intrapulmonary Recombinant Factor VII as an Effective Treatment for Diffuse Alveolar Hemorrhage
Authors: Baker Mary S. , Diab Khalil J. , Carlos W. Graham , Mathur Praveen
Published: June 2016

Background:

The diffuse alveolar hemorrhage (DAH) syndrome is a life-threatening pulmonary complication related to systemic vasculitides, posthematopoietic stem cell transplantation, drugs, or toxins. Once DAH develops, the mortality rate is as high as 50% to 80%. Initial treatment consists of high-dose steroids and supportive measures, including mechanical ventilation. We present a case series of 6 patients treated with intrapulmonary recombinant factor VIIa (rFVIIa) to treat refractory DAH.

Methods:

Six patients with DAH were treated with intrapulmonary instillation of rFVIIa. Doses were divided equally between the right and the left lungs. Doses were 30, 50, or 60 mcg/kg and frequencies varied from a single administration to repeated doses on subsequent days on the basis of the clinical response. All patients received high-dose steroids, and 4 also received an aminocaproic acid infusion.

Results:

Intrapulmonary rVFIIa treated DAH effectively in 5 of 6 patients. Doses used were smaller and less frequent than those described previously.

Conclusions:

Intrapulmonary factor VII is an effective adjunctive treatment for DAH. We achieved treatment success with both smaller and less frequent doses than those described previously. This may be a good therapeutic option for DAH, particularly when standard therapies have failed or bleeding is immediately life threatening. It is possible that intrapulmonary rFVIIa could save costs, while improving the intensive care unit length of stay. Further prospective studies are needed to assess the optimal dose and frequency for adequate therapeutic efficacy.
Topical Lidocaine Does Not Exaggerate Laryngomalacia in Infants During Flexible Bronchoscopy Under Propofol Anesthesia
Authors: von Ungern-Sternberg Britta S. , Trachsel Daniel , Zhang Guicheng , Erb Thomas O. , Hammer Jürg
Published: June 2016

Background:

Topical lidocaine has been found to result in overestimation of the severity of laryngomalacia in infants undergoing flexible bronchoscopy under conscious sedation with midazolam and nalbuphine. This effect has never been confirmed and may depend on the level of sedation and the drugs used. We assessed the effect of topical lidocaine on laryngomalacia in infants undergoing flexible bronchoscopy under general anesthesia with propofol.

Methods:

Thirteen infants with congenital stridor referred to diagnostic flexible video-bronchoscopy were studied under propofol anesthesia before and 3 minutes after topical lidocaine administration to the larynx at a dose of 3 mg/kg body weight. Laryngomalacia was scored using 60 seconds video recordings of the larynx before and after lidocaine administration in random order by 2 independent blinded observers using the previously described arytenoid score (AS), epiglottis score (ES), and the total score (TS=AS+ES).

Results:

No significant differences in AS, ES, and laryngomalacia score were found between the prelidocaine and postlidocaine assessments by the 2 raters. The intraclass correlation coefficients were 0.995 (95% confidence interval, 0.986-0.998) and 0.975 (0.930-0.991) and 0.989 (0.971-996) for AS, ES, and TS, respectively.

Conclusions:

The assessment of laryngomalacia is not affected by topical lidocaine under propofol anesthesia. The lidocaine effect on laryngomalacia may vary depending on the medication regime used and the depth of procedural sedation.
Transbronchial Cryobiopsy in Interstitial Lung Disease
Authors: Cascante José A. , Cebollero Pilar , Herrero Sonia , Yagüe Adriana , Echegoyen Ana , Elizalde Jesús , Hueto Javier
Published: June 2016

Background:

A definitive and specific diagnosis of interstitial lung disease (ILD) often requires a histologic analysis of the lung parenchyma. A transbronchial biopsy with forceps has a limited diagnostic yield for idiopathic interstitial pneumonias. The incorporation of a transbronchial lung cryobiopsy for diagnosing ILD appears to be very promising, although there are only a few published studies in this regard. Our paper shows the results of using this technique in our center.

Methods:

This was a prospective study including 55 patients with ILD diagnosed from January 2012 to January 2015. The methodology used, the overall diagnostic yield, and the number and the location of samples, in addition to complications, have been reported.

Results:

In 38 (69%), 10 (20.8%), and 7 (12.7%) cases, we obtained a certain, highly likely, and unclassifiable diagnosis of interstitial pneumonia, respectively. With 18 cases, usual interstitial pneumonia was the most common diagnosis. The most common complication was a pneumothorax in 8 patients (14.5%).

Conclusions:

A transbronchial lung cryobiopsy using a flexible cryoprobe has a good diagnostic yield and might be an alternative to consider in cases of diffuse ILD in which a histologic sample is required for diagnosis. This technique could avoid a large number of surgical biopsies.
Massachusetts Health Reform’s Effect on Hospitals’ Racial Mix of Patients and on Patients’ Use of Safety-net Hospitals
Authors: Lasser Karen E. , Hanchate Amresh D. , McCormick Danny , Chu Chieh , Xuan Ziming , Kressin Nancy R.
Published: June 2016

Background:

Because of residential segregation and a lack of health insurance, minorities often receive care in different facilities than whites. Massachusetts (MA) health reform provided insurance to previously uninsured patients, which enabled them to potentially shift inpatient care to nonminority-serving or nonsafety-net hospitals.

Objectives:

Examine whether MA health reform affected hospitals’ racial mix of patients, and individual patients’ use of safety-net hospitals.

Research Design:

Difference-in-differences analysis of 2004–2009 inpatient discharge data from MA, compared with New York (NY), and New Jersey (NJ), to identify postreform changes, adjusting for secular changes.

Subjects:

(1) Hospital-level analysis (discharges): 345 MA, NY, and NJ hospitals; (2) patient-level analysis (patients): 39,921 patients with ≥2 hospitalizations at a safety-net hospital in the prereform period.

Measures:

Prereform to postreform changes in percentage of discharges that are minority (black and Hispanic) at minority-serving hospitals; adjusted odds of patient movement from safety-net hospitals (prereform) to nonsafety-net hospitals (postreform) by age group and state.

Results:

Treating NJ as the comparison state, MA reform was associated with an increase of 5.8% (95% CI, 1.4%−10.3%) in the percentage of minority discharges at MA minority-serving hospitals; with NY as the comparison state, the change was 2.1% (95% CI, −0.04% to 4.3%). Patient movement from safety-net to nonsafety-net hospitals was greater in MA than comparison states (difference-in-differences adjusted OR=1.3; 95% CI, 1.0–1.7; P=0.04).

Conclusions:

Following MA health reform, the safety-net remains an important component of the health care system.
Prototype End-of-Life Quality Measures Based on MDS 3 Data
Authors: Mukamel Dana B. , Ladd Heather , Caprio Thomas , Temkin-Greener Helena
Published: June 2016

Background:

The Nursing Home Compare (NHC) report card does not include end-of-life (EOL) quality measures (QMs).

Objectives:

To develop and examine the properties of EOL QMs.

Subjects:

A total of 39,590 nursing home decedents in 626 facilities in New York State in fiscal year 2012.

Design:

Statistical analyses of Minimum Data Set 3 data, including multivariable regression analyses and descriptive statistics.

Measures:

Death in the hospital, number of hospitalizations, pain, and depression during the last 90 days before death.

Results:

Overall, 32% of residents died in the hospital. They averaged 0.49 hospitalizations in the last 90 days before death, 10% reported moderate to severe pain, and 17% had depressive symptoms. The EOL QMs exhibited variation across facilities similar to that observed for other QMs. They showed low or moderate correlations. The pain and depression QMs were significantly better among nursing homes ranked by NHC as 4 and 5 stars compared with those ranked as 1 and 2 stars for most dimensions. The hospitalizations QMs were significantly better among nursing homes ranked by NHC as 4 and 5 stars compared with those ranked as 1 and 2 stars only when compared on the staffing dimension.

Conclusions:

The Minimum Data Set 3 includes much information that can be used to assess quality of EOL care in nursing homes. The prototype measures we developed could be improved if information about advance directives and the nonclinical aspects of care, such as comfort and emotional support for both the resident and the family and respect for resident and family preferences, were collected.
Comparison of Long-run Trends in 30-day Readmission by Degrees of Medicare Payment Cuts
Authors: Shen Yu-Chu , Wu Vivian Y.
Published: June 2016

Background and Objective:

The Affordable Care Act enacted significant Medicare payment reductions to providers, yet long-term effects of such major reductions on patient outcomes remain uncertain. Using the 1997 Balanced Budget Act (BBA) as an experiment, we compare long-run trends in 30-day readmission across hospitals with different amount of payment cuts.

Research Design, Subjects, and Measures:

Using 100% Medicare claims between 1995 and 2011 and instrumental variable hospital fixed-effects regression models, we compared changes in 30-day readmission trends for 5 leading Medicare conditions between urban hospitals facing small, moderate, and large BBA payment reductions across 4 periods [1995–1997 (pre-BBA period), 1998–2000, 2001–2005, 2006–2001]. Patient sample includes Medicare patients who were admitted to general, acute, urban, short-stay hospitals in the United States 1995–2011. Sample size ranges from 1.4 million patients for acute myocardial infarction to 3 million for pneumonia.

Results:

We found that 30-day readmission trends diverged post-BBA (2001–2005) between hospitals facing small and large payment cuts, where large-cut hospitals experience slower improvement in readmission rates relative to small-cut hospitals. The gap between small-cut and large-cut hospitals readmission trend was 6% for acute myocardial infarction, 4% for congestive heart failure and pneumonia (all P<0.01) in the 2001–2005 period. The gaps between hospitals were eliminated by the 2006–2011 period as the effect of BBA naturally dissipated over time.

Conclusions:

Although payment-cut differences are associated with widening gaps in readmission rates across hospitals, the negative association appears to dissipate in the long run.
Measuring Health-related Quality of Life in Teens With and Without Depression
Authors: Lynch Frances L. , Dickerson John F. , Feeny David H. , Clarke Gregory N. , MacMillan Alex L.
Published: June 2016

Purpose:

To provide empirical evidence on the performance of common measures in assessing health-related quality of life (HRQL) in depressed and nondepressed youth. These measures can be used in research trials, cost-effectiveness studies, and to help develop policy for treating youth depression.

Background:

Depression is one of the most common mental disorders among adolescents, with a chronic, episodic course marked by considerable impairment. Data on HRQL for teens with depression could more fully demonstrate the burden of depression and help to evaluate the comparative effectiveness of teen depression services, which in turn can be used to inform public and clinical policies.

Methods:

We collected data on depression and HRQL from 392 depressed and nondepressed teens aged 13–17.

Results:

Generic mental health, disease-specific, and generic preference-based measures of HRQL all do a reasonable job of distinguishing teens with and without depression and between teens with differing levels of depression. Generic mental health and disease-specific measures provide valuable information on burden of disease and perform well. For the purpose of economic evaluation, the HUI-3 and EQ-5D perform somewhat better than other preference-based measures. These results can aid future research on teens with depression by helping to guide which HRQL instruments are most useful in this population and can help to quantify the burden of depression in teens for policy and clinical planning.
Influence of repetitive peripheral magnetic stimulation on neural plasticity in the motor cortex related to swallowing
Authors: Momosaki Ryo , Kakuda Wataru , Yamada Naoki , Abo Masahiro
Published: June 2016

The aim of this study was to evaluate the effect of repetitive peripheral magnetic stimulation at two different frequencies (20 and 30 Hz) on cortical excitability in motor areas related to swallowing in healthy individuals. The study participants were 10 healthy normal volunteers (two women and eight men, age range 25–36 years). Repetitive peripheral magnetic stimulation was applied to the submandibular muscle using a parabolic coil at the site where contraction of the suprahyoid muscles was elicited. Stimulation was continued for 10 min (total 1200 pulses) at 20 Hz on 1 day and at 30 Hz on another day, with the stimulation strength set at 90% of the intensity that elicited pain. The motor-evoked potential amplitude of suprahyoid muscles was assessed before, immediately after, and 30 min after stimulation. Stimulations at both 20 and 30 Hz significantly increased motor-evoked potential amplitude (P<0.05), with the increase maintained until 30 min after stimulation. The motor-evoked potential amplitude immediately after stimulation was not significantly different between the 20 and 30 Hz frequencies. The results indicated that repetitive magnetic stimulation increased motor-evoked potential amplitude of swallowing muscles, suggesting facilitation of the motor cortex related to swallowing in healthy individuals.
Measuring functioning and disability after a disaster: results from the typhoon Haiyan/Yolanda-affected areas of the Philippines
Authors: Leonardi Matilde , Talampas Rolando , Chatterji Somnath , Kostanjsek Nenad F. , Regadio Crisanto , Tarroja Maria C. , Schiavolin Silvia , Naidoo Nirmala , Raggi Alberto , Pindog Mona , Zayas Jerome , Zagaria Nevio
Published: June 2016

The most commonly reported data after natural disasters are the number of deceased and displaced and the structural and economic damage, whereas disability data are often lacking. Our study assessed disability among the survivors of the Haiyan/Yolanda typhoon that struck Philippines in 2013 and is aimed to identify which context-level variables are associated with higher disability. We used a cross-sectional design and administered a household questionnaire, an individual sociodemographic questionnaire, and the WHODAS 2.0 to 1982 adults. Logistic regression analysis was carried out to address the degree to which demographic variables, effects of the typhoon, individual health state, and rural or urban residence were associated with higher disability. Those aged above 65, employed individuals, students, those not living in their households, and those with one or more health condition or rating their own as health moderate or very poor had higher likelihood of having severe disability. Survivors living in rural contexts and those who received tools/materials to repair their houses were less likely to have higher disability. This study outlines that disability can and should be used as an indicator in surveys after emergencies to identify the most vulnerable groups, thus guiding policies, reconstruction strategies, and health and social interventions.
Cognitive Representation of Treatment-Related Symptoms in Older Adults With Cancer
Authors: Loerzel Victoria
Published: June 2016

Background:

Adults, 65 years or older, are the most common age group diagnosed with cancer. However, little is known about their beliefs (representations) regarding treatment-related symptoms or how they make decisions to manage those symptoms at home.

Objective:

The aim of this study is to explore symptom representation of treatment-related symptoms in older adults with cancer.

Methods:

A total of 100 older adults in treatment for cancer completed a standardized measure of symptom representation. Demographic and other patient variables were also collected. Analysis of variance, t tests, and Pearson correlations were used for analysis.

Results:

Fatigue was both the most common and most noted symptom; however, several most noted symptoms were not common. Overall, older adults believed symptoms were caused by either their cancer or treatment and were unsure if symptoms would last a long time. They were able to recognize symptom consequences but were unsure about their ability to control symptoms. Adults who reported more comorbid illnesses and a higher number of symptoms believed that treatment-related symptoms had higher consequences.

Conclusions:

Findings suggest that older adults experience symptom-related consequences but question the impact that their actions will have on symptom severity. This may contribute to older adult’s lack of active symptom self-management.

Implications for Practice:

Patient education strategies need to address these representations and new interventions may need to be developed to reinforce symptom consequences and empower older adults to self-manage symptoms.
“I Had a Little Bit of a Bloke Meltdown…But the Next Day, I Was Up”
Authors: Newman Christy E. , Gray Rebecca , Brener Loren , Jackson L. Clair , Dillon Anthony , Saunders Veronica , Johnson Priscilla , Treloar Carla
Published: June 2016

Background:

Although cancer in indigenous populations is receiving increased research attention, there is a gap in understanding the particular experiences of Aboriginal men.

Objective:

The aim of this study is to integrate a range of primary and secondary accounts of the experiences of Aboriginal men in engaging with a cancer diagnosis and treatment in Australia.

Methods:

Secondary analysis of qualitative interviews (n = 54) conducted between 2008 and 2011 revealed recurrent themes regarding the cancer experiences of Aboriginal men in a subset of participant interviews (n = 23). The analysis reports themes that spanned the accounts of Aboriginal men with cancer (n = 6) and those of their carers (n = 12) and clinicians (n = 5).

Results:

Recurrent beliefs about the cancer experiences of Aboriginal men included that they “avoid seeking help” for health matters, including cancer symptoms, and to “get on with it,” “not talk about it,” and “manage without fuss” after a cancer diagnosis. Although some men described having to “accept vulnerability,” emphasis was placed on appreciating men’s desire to “protect cultural roles” and “connect with family and culture” throughout care and treatment, including through humor.

Conclusions:

Men’s accounts of the experiences of cancer diagnosis and care reveal more than simply individual challenge, extending to encompass the very real social and economic implications of illness and vulnerability for Aboriginal men today.

Implications for Practice:

Aboriginal men could be better engaged with cancer diagnosis and treatment if greater attention was paid to recognizing preferred approaches, including pragmatism and humor, and supporting connections to family and culture throughout the cancer journey.
Retrograde Degeneration of Retinal Ganglion Cells Secondary to Head Trauma
Authors: Vien Lee , DalPorto Christina , Yang David
Published: June 2016

Purpose

To discuss the clinical case of a patient with transsynaptic retrograde degeneration (TRD) demonstrated by progressive retinal nerve fiber layer loss documented by serial spectral domain optical coherence tomography secondary to traumatic brain injury after 2 months post-trauma.

Case Report

A 25-year-old Caucasian male patient presented to a polytrauma rehabilitation center (PRC) for evaluation and treatment secondary to a severe traumatic brain injury (TBI) from a motorcycle accident 2 months before. Spectral-domain optical coherence tomography (SD-OCT) was completed at intervals that ranged between 8 and 42 days for a duration of 119 days. A comparison to the pre-trauma SD-OCT 10 months before revealed progressive thinning of the retinal nerve fiber layer (RNFL) in both eyes over multiple follow-ups post-trauma. Humphrey visual field (HVF) testing revealed an incomplete congruous right homonymous hemianopsia that gradually improved over the follow-ups. Analysis of the macular ganglion cell-inner plexiform layer (GCIPL) thickness displayed loss that corresponded to the pattern of visual field defect.

Conclusions

TRD can occur as soon as 2 months after severe TBI with damage posterior to the lateral geniculate nucleus. Progressive RNFL loss can be tracked with SD-OCT, and the rate of thinning may slowly stabilize over time. Visual field defects can improve months after the trauma but may not correspond to the progressive RNFL loss detected by SD-OCT.
The Challenges of Caring for Long-Stay Patients in the PICU*
Authors: Geoghegan Sophie , Oulton Kate , Bull Catherine , Brierley Joe , Peters Mark , Wray Jo
Published: June 2016

Objective:

Compared to shorter-stay patients, caring for long-stay patients in the ICU entails a disproportionate burden for staff. Our objective was to gain a deeper understanding of the impact on staff of caring for children who have a prolonged stay on the PICU.

Design:

Qualitative study based on semi-structured interviews. Data were analyzed using the Framework approach.

Setting:

Children’s tertiary hospital.

Participants:

Seventeen members of staff (7 psychosocial staff, 7 nurses, 3 consultants) working in the PICU, neonatal ICU, or cardiac ICU (PICU will be used to encompass neonatal ICU, cardiac ICU, and PICU for the remainder of this article).

Interventions:

Semi-structured, tape-recorded interviews.

Measurements and Main Results:

Staff reported both positive and challenging aspects of caring for long-stay patients in the PICU. Five key areas relating to the challenges of caring for long-stay patients were identified: staff expectations about their work, characteristics of the patient group, the impact on staff, the impact on the wider unit, and the availability of support. Staff views were often compounded by individual cases they had been involved with or had heard about which fell at either end of the spectrum of “good” and “bad”.

Conclusions:

Whilst there are reported benefits associated with caring for long-stay patients, there are a number of challenges reported that may have implications for staff and the wider unit. When caring for a particular sub-group of long-stay patients, staff may be more likely to experience negative impacts. A key priority for the PICU is to ensure that support mechanisms are timely, accessible, and allow staff to explore their own reactions to their work.
Construct Validity and Responsiveness of the Pediatric Quality of Life Inventory 4.0 Generic Core Scales and Infant Scales in the PICU*
Authors: Aspesberro François , Fesinmeyer Megan D. , Zhou Chuan , Zimmerman Jerry J. , Mangione-Smith Rita
Published: June 2016

Objectives:

To assess the construct validity and the responsiveness of the Pediatric Quality of Life Inventory 4.0 Generic Core Scales and Infant Scales in the medical-surgical (PICU) and cardiac PICU.

Design/Setting/Participants:

Prospective cohort study of 367 inpatients admitted either to the PICU or the cardiac ICU at Seattle Children’s Hospital from January 2012 to June 2013. Parent/caregiver and child (≥ 8 yr old, developmentally appropriate, and critical illness resolved) Pediatric Quality of Life Inventory scores were obtained within 24 hours of PICU/cardiac ICU discharge and subsequently at 4–12 weeks following hospital discharge. Of the 491 eligible participants invited to participate, 367 (74.7% response rate) completed the Pediatric Quality of Life Inventory survey at ICU discharge, and of these, 263 (71.7% follow-up response rate) completed the follow-up survey 4–12 weeks after hospital discharge.

Measurements and Main Results:

Responsiveness was assessed by calculating improvement scores (difference between follow-up and ICU discharge scores, Δ Pediatric Quality of Life Inventory). Construct validity was examined by comparing mean improvement scores for known groups differing by medical complexity. At follow-up, ∆ Pediatric Quality of Life Inventory scores were as follows (mean ± sd): physical domain, 34.8 ± 32.0; and psychosocial domain, 23.1 ± 23.5. Patients with complex chronic or noncomplex chronic disease had physical functioning improvement scores that were 17.4 points (95% CI, –28.3 to –6.5; p < 0.001) and 19.5 points (95% CI, –30.4 to –8.5; p < 0.002) lower than children with no chronic illness, respectively. Patients with complex chronic disease exhibited psychosocial improvement scores that were 9.6 points (95% CI, –18.4 to –0.8; p < 0.033) lower than patients without chronic disease. Patients with noncomplex chronic disease had similar psychosocial improvement scores when compared with patients without chronic disease.

Conclusions:

As a measure of health-related quality of live, Pediatric Quality of Life Inventory demonstrated responsiveness and construct validity in a broad population of critically ill children. This measure represents a patient-centered clinically meaningful patient-or-parent-reported outcome measure for pediatric research assessing the clinical effectiveness of PICU/cardiac ICU interventions. When using health-related quality of life recovery as an outcome measure to assess clinical effectiveness in the PICU/cardiac ICU setting, measuring and controlling for the level of medical complexity is important in order to understand the true impact of clinical interventions.
Aberrant Expression of Anaplastic Lymphoma Kinase in Ovarian Carcinoma Independent of Gene Rearrangement
Authors: Tang Shaoxian , Yang Fei , Du Xiang , Lu Yongming , Zhang Ling , Zhou Xiaoyan
Published: June 2016

Ovarian carcinoma is the leading cause of death from gynecologic malignancies. The oncogenic role of anaplastic lymphoma kinase (ALK) is well characterized in many hematopoietic and solid tumors. ALK expression in ovarian carcinoma has been reported but the exact status of ALK protein and its association with clinicopathologic features requires further investigation. ALK expression was determined by immunohistochemistry in 110 primary ovarian carcinomas, including 85 cases of serous carcinoma and 25 cases of mucinous carcinoma. Fluorescence in situ hybridization (FISH) and real-time reverse transcription polymerase chain reaction (RT-PCR) were used for evaluating ALK translocation in ALK-positive ovarian carcinomas. Among 110 ovarian carcinomas, 23 (20.9%) cases were ALK positive by immunohistochemistry. All ALK-positive cases were ovarian high-grade serous carcinoma. ALK expression was detected in 23/85 (27.1%) ovarian serous carcinoma and 0/25 (0%) in ovarian mucinous carcinoma. None of the 23 ALK IHC-positive cases harbored ALK gene translocations by FISH or RT-PCR. ALK protein expression was associated with patient age, tumor stage, and histologic type. Specifically, the probability of ALK protein expression was significantly higher in high-grade serous carcinomas in older patients (above 50 y) with advanced disease (FIGO stage III and IV) compared with the low-grade serous and mucinous carcinomas in younger patients with relatively early disease. In conclusion, aberrant ALK expression is observed in ovarian serous carcinoma but not in mucinous carcinoma, is independent of gene translocation, and might be associated with progression and prognosis.
Viral Decay Dynamics and Mathematical Modeling of Treatment Response: Evidence of Lower in vivo Fitness of HIV-1 Subtype C
Authors: Shet Anita , Nagaraja Pradeep , Dixit Narendra M.
Published: June 2016

Background:

Despite the high prevalence of HIV-1 subtype C (HIV-1C) worldwide, information on HIV-1C viral dynamics and response to antiretroviral therapy (ART) is limited. We sought to measure viral load decay dynamics during treatment and estimate the within-host basic reproductive ratio, R0, and the critical efficacy, εc, for successful treatment of HIV-1C infection.

Methods:

Individuals initiated on first-line ART in India and monitored for 6 months of treatment were considered. Viral load, CD4+ count, and adherence data were collected at baseline, 4, 12, 16 and 24 weeks after ART initiation. Drug resistance genotyping was performed at baseline. R0 and εc were estimated using a mathematical model.

Results:

Among 257 patients with complete data, mean baseline viral load was 5.7 log10 copies per milliliter and median CD4+ count was 165 cells per cubic millimeter. Primary drug resistance was present in 3.1% at baseline. At 6 months, 87.5% had undetectable viral load, indicating excellent response to ART despite high baseline viremia. After excluding those with transmitted resistance, suboptimal adherence and viral rebound, data from 112 patients were analyzed using a mathematical model. We estimated the median R0 to be 5.3. The corresponding εc was ∼0.8.

Conclusions:

These estimates of R0 and εc are smaller than current estimates for HIV-1B, suggesting that HIV-1C exhibits lower in vivo fitness compared with HIV-1B, which allows successful treatment despite high baseline viral loads. The lower fitness, and potentially lower virulence, together with high viral loads may underlie the heightened transmission potential of HIV-1C and its growing global spread.
Effect of Renal Function on Gadolinium-Related Signal Increases on Unenhanced T1-Weighted Brain Magnetic Resonance Imaging
Authors: Cao Yan , Zhang Yang , Shih George , Zhang Yan , Bohmart Andrew , Hecht Elizabeth M. , Prince Martin R.
Published: June 2016

Objectives

The purpose of this study was to determine if renal function affects signal changes in the deep brain nuclei on unenhanced T1-weighted images after administration of linear gadolinium-based contrast agents (GBCAs).

Methods

An electronic medical records search of 2 large medical centers identified 25 patients who received linear GBCA while on hemodialysis and had unenhanced T1-weighted images of the brain before and after. The dentate-to-cerebellar peduncle (DCP) ratio, globus pallidus-to-mid thalamus (GPT) ratio, and choroid plexus-to-nearby white matter ratio were measured and compared with 25 age/sex/GBCA exposure–matched control patients with normal or near-normal renal function (estimated glomerular filtration rate >60 mL/min per 1.73 m2). Two additional control groups included 13 patients on hemodialysis without GBCA exposure and 13 age/sex-matched patients with estimated glomerular filtration rate greater than 60 mL/min per 1.73 m2.

Results

Hemodialysis patients (n = 25) with an average of 1.8 linear GBCA administrations had a 4.9% mean increase (1.00 ± 0.04 vs 1.05 ± 0.05; P < 0.001) in DCP, which was greater than the 1.6% change (0.99 ± 0.04 vs 1.00 ± 0.05; P = 0.08) observed in matched controls (P = 0.01). There was no significant signal change in the DCP ratio in the 13 hemodialysis patients (0.99 ± 0.04 vs 0.99 ± 0.04; P = 0.78) and 13 age/sex-matched patients (0.99 ± 0.02 vs 0.99 ± 0.03; P = 0.78) who did not receive GBCA. The hemodialysis patients had a baseline GPT that was higher than nondialysis patients (P < 0.001). However, the GPT change after GBCA administration was not significantly different from controls. Increased signal in the choroid plexus on unenhanced T1-weighted images after GBCA administration was noted in hemodialysis patients (0.72 ± 0.20 vs 0.86 ± 0.23; P = 0.006); however, a multivariate analysis showed this to be primarily related to hemodialysis (P = 0.003) with only a trend toward relating to GBCA exposure (P = 0.07).

Conclusions

Hemodialysis patients receiving linear GBCA have greater dentate nucleus signal increases on unenhanced T1-weighted images, suggesting that renal function may affect the rate of gadolinium accumulation in the brain after linear GBCA-enhanced magnetic resonance imaging.
Ultrasonographic and Electrophysiological Evaluation of the Ulnar Nerve in Patients Diagnosed With Carpal Tunnel Syndrome
Authors: Kose Ozlece Hatice , Huseyinoglu Nergiz , Gok Mustafa , Ilik Faik
Published: June 2016

Purpose:

In this study, we evaluated the ulnar nerve of patients diagnosed with carpal tunnel syndrome (CTS) using electrophysiology and ultrasonography.

Methods:

The study included 86 patients (136 hands) and 39 controls (78 hands) with normal electrophysiological assessment. According to Bland's classification, patients were divided into group 1 (grades 1–3 CTS) or group 2 (grades 4–6 CTS). The ulnar nerve was evaluated at the wrist using nerve conduction studies and ultrasonography.

Results:

The sensory velocity was slower in group 2 than in group 1 (P < 0.001), slower in group 2 than in controls (P < 0.001), and slower in group 1 than in controls (P < 0.005). Although the ultrasonography results showed a reduction in the ulnar nerve cross-sectional area in group 1 compared with controls, the difference was not statistically significant. However, the reduction was significant in group 2 compared with group 1 and controls (P < 0.001).

Conclusions:

Based on our study results, the ulnar nerve is affected electrophysiologically and morphologically in patients with CTS, especially those with advanced-stage CTS.
Cancer cells with alternative lengthening of telomeres do not display a general hypersensitivity to ATR inhibition
Authors: Deeg Katharina I. , Chung Inn , Bauer Caroline , Rippe Karsten
Published: June 2016

Telomere maintenance is a hallmark of cancer as it provides cancer cells with cellular immortality. A significant fraction of tumors uses the alternative lengthening of telomeres (ALT) pathway to elongate their telomeres and to gain an unlimited proliferation potential. Since the ALT pathway is unique to cancer cells, it represents a potentially valuable, currently unexploited target for anticancer therapies. Recently, it was proposed that ALT renders cells hypersensitive to ataxia telangiectasia-and RAD3-related (ATR) protein inhibitors (Flynn et al., Science 347, 273). Here, we measured the response of various ALT or telomerase positive cell lines to the ATR inhibitor VE-821. In addition, we compared the effect of the inhibitor on cell viability in an isogenic cell line, in which ALT was active or suppressed. In these experiments a general ATR inhibitor sensitivity of cells with ALT could not be confirmed. We rather propose that the observed variations in sensitivity reflect differences between cell lines that are unrelated to ALT.
The Lair: A resource for exploratory analysis of published RNA-Seq data
Authors: Pimentel Harold , Sturmfels Pascal , Bray Nicolas , Melsted Páll , Pachter Lior
Published: June 2016

Increased emphasis on reproducibility of published research in the last few years has led to the large-scale archiving of sequencing data. While this data can, in theory, be used to reproduce results in papers, it is typically not easily usable in practice. We introduce a series of tools for processing and analyzing RNA-Seq data in the Short Read Archive, that together have allowed us to build an easily extendable resource for analysis of data underlying published papers. Our system makes the exploration of data easily accessible and usable without technical expertise. Our database and associated tools can be accessed at The Lair:http://pachterlab.github.io/lair
Large-scaletrans-eQTLs affect hundreds of transcripts and mediate patterns of transcriptional co-regulation Short:trans-eQTLs reveal patterns of transcriptional co-regulation
Authors: Brynedal Boel , Choi JinMyung , Raj Towfique , Bjornson Robert , Stranger Barbara E , Neale Benjamin M , Voight Benjamin F , Cotsapas Chris
Published: June 2016

Genetic variation affecting gene regulation is a driver of phenotypic differences between individuals and can be used to uncover how biological processes are organized in a cell. Although detectingcis-eQTLs is now routine,trans-eQTLs have proven more challenging to find due to the modest variance explained and the multiple testing burden when comparing millions of SNPs for association to thousands of transcripts. Here, we provide evidence for the existence oftrans-eQTLs by looking for SNPs associated with the expression of multiple genes simultaneously. We find substantial evidence oftrans-eQTLs, with an 1.8-fold enrichment in nominally significant markers in all three populations and significant overlap between results across the populations. Thesetrans-eQTLs target the same genes and show the same direction of effect across populations. We define a high-confidence set of eight independenttrans-eQTLs which are associated to multiple transcripts in all three populations, and affect the same targets in all three populations with the same direction of effect. We then show that target transcripts oftrans-eQTLs encode proteins that interact more frequently than expected by chance, and are enriched for pathway annotations indicative of roles in basic cell homeostasis. Thus, we have demonstrated thattrans-eQTLs can be accurately identified even in studies of limited sample size.
Cryptic diversity and multiple origins of the widespread mayfly species groupBaetis rhodani(Ephemeroptera: Baetidae) on northwestern Mediterranean islands
Authors: Bisconti Roberta , Canestrelli Daniele , Tenchini Roberta , Belfiore Carlo , Buffagni Andrea , Nascetti Giuseppe
Published: June 2016

How the often highly endemic biodiversity of islands originated has been debated for decades and it remains a fervid research ground. Here, using mitochondrial and nuclear gene sequence analyses, we investigate the diversity, phylogenetic relationships, and evolutionary history of the mayflyBaetis gr. rhodanion the three largest north-western Mediterranean islands (Sardinia, Corsica, Elba). We identify three distinct, largely co-distributed, and deeply differentiated lineages, with divergences tentatively dated back to the Eocene-Oligocene transition. Bayesian population structure analyses reveal a lack of gene exchange between them, even at sites where they are syntopic, indicating that these lineages belong to three putative species. Their phylogenetic relationships with continental relatives, together with the dating estimates, support a role for three processes contributing to this diversity: (1) vicariance, primed by microplate disjunction and oceanic transgression; (2) dispersal from the continent; and (3) speciation within the island group. Thus, our results do not point toward a prevailing role for any of the previously invoked processes. Rather, they suggest that a variety of processes equally contributed to shape the diverse and endemic biota of this group of islands.
Identification of microsporidia host-exposed proteins reveals a repertoire of large paralogous gene families and rapidly evolving proteins
Authors: Reinke Aaron W. , Balla Keir M. , Bennett Eric J. , Troemel Emily R.
Published: June 2016

Pathogens use a variety of secreted and surface proteins to interact with and manipulate their hosts, but a systematic approach for identifying such proteins has been lacking. To identify these ‘host-exposed’ proteins, we used spatially restricted enzymatic tagging followed by mass spectrometry analysis ofC. elegansinfected with two species ofNematocidamicrosporidia. We identified 82 microsporidia proteins inside of intestinal cells, including several pathogen proteins in the nucleus. These microsporidia proteins are enriched in targeting signals, are rapidly evolving, and belong to large,Nematocida-specific gene families. We also find that large, species-specific families are common throughout microsporidia species. Our data suggest that the use of a large number of rapidly evolving species-specific proteins represents a common strategy for these intracellular pathogens to interact with their hosts. The unbiased method described here for identifying potential pathogen effectors represents a powerful approach for the study of a broad range of pathogens.
Spatial Capture-Recapture with Partial Identity: An Application to Camera Traps
Authors: Augustine Ben C. , Royle J. Andrew , Kelly Marcella J. , Satter Christopher B. , Alonso Robert S. , Boydston Erin E. , Crooks Kevin R.
Published: June 2016

Camera trapping surveys frequently capture individuals whose identity is only known from a single flank. The most widely used methods for incorporating these partial identity individuals into density analyses discard some of the partial identity capture histories, reducing precision, and while not previously recognized, introducing bias. Here, we present the spatial partial identity model (SPIM), which uses the spatial location where partial identity samples are captured to probabilistically resolve their complete identities, allowing all partial identity samples to be used in the analysis. We show that the SPIM out-performs other analytical alternatives. We then apply the SPIM to an ocelot data set collected on a trapping array with double-camera stations and a bobcat data set collected on a trapping array with single-camera stations. The SPIM improves inference in both cases and in the ocelot example, individual sex determined from photographs is used to further resolve partial identities, one of which is resolved to near certainty. The SPIM opens the door for the investigation of trapping designs that deviate from the standard 2 camera design, the combination of other data types between which identities cannot be deterministically linked, and can be extended to the problem of partial genotypes.
The evolutionary basis of premature migration in Pacific salmon highlights the utility of genomics for informing conservation
Authors: Prince Daniel J. , O’Rourke Sean M. , Thompson Tasha Q. , Ali Omar A. , Lyman Hannah S. , Saglam Ismail K. , Hotaling Thomas J. , Spidle Adrian P. , Miller Michael R.
Published: June 2016

The delineation of conservation units (CUs) is a challenging issue that has profound implications for minimizing the loss of biodiversity and ecosystem services. CU delineation typically seeks to prioritize evolutionary significance and genetic methods play a pivotal role in the delineation process by quantifying overall differentiation between populations. While CUs that primarily reflect overall genetic differentiation do protect adaptive differences between distant populations, they do not necessarily protect adaptive variation within highly connected populations. Advances in genomic methodology facilitate the characterization of adaptive genetic variation, but the potential utility of this information for CU delineation is unclear. Here we use genomic methods to investigate the evolutionary basis of premature migration in Pacific salmon, a complex behavioral and physiological adaptation that exists within highly-connected populations and has experienced severe declines. Strikingly, we find that premature migration is associated with the same single locus across multiple populations in each of two different species. Patterns of variation at this locus suggest that the premature migration alleles arose from a single evolutionary event within each species and were subsequently spread to distant populations through straying and positive selection. Our results reveal that complex adaptive variation can depend on rare mutational events at a single locus, demonstrate that CUs reflecting overall genetic differentiation can fail to protect evolutionarily significant variation that has substantial ecological and societal benefits, and suggest that a supplemental framework for protecting specific adaptive variation will sometimes be necessary to prevent the loss of significant biodiversity and ecosystem services.