bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Among ICU Congestion, ICU Admission Decision, and Patient Outcomes*
Authors: Kim Song-Hee , Chan Carri W. , Olivares Marcelo , Escobar Gabriel J.
Published: June 2016

Objectives:

To employ automated bed data to examine whether ICU occupancy influences ICU admission decisions and patient outcomes.

Design:

Retrospective study using an instrumental variable to remove biases from unobserved differences in illness severity for patients admitted to ICU.

Setting:

Fifteen hospitals in an integrated healthcare delivery system in California.

Patients:

Seventy thousand one hundred thirty-three episodes involving patients admitted via emergency departments to a medical service over a 1-year period between 2008 and 2009.

Interventions:

None.

Measurements and Main Results:

A third of patients admitted via emergency department to a medical service were admitted under high ICU congestion (more than 90% of beds occupied). High ICU congestion was associated with a 9% lower likelihood of ICU admission for patients defined as eligible for ICU admission. We further found strong associations between ICU admission and patient outcomes, with a 32% lower likelihood of hospital readmission if the first inpatient unit was an ICU. Similarly, hospital length of stay decreased by 33% and likelihood of transfer to ICU from other units—including ICU readmission if the first unit was an ICU—decreased by 73%.

Conclusions:

High ICU congestion is associated with a lower likelihood of ICU admission, which has important operational implications and can affect patient outcomes. By taking advantage of our ability to identify a subset of patients whose ICU admission decisions are affected by congestion, we found that, if congestion were not a barrier and more eligible patients were admitted to ICU, this hospital system could save approximately 7.5 hospital readmissions and 253.8 hospital days per year. These findings could help inform future capacity planning and staffing decisions.
Concurrent and lagged relations between momentary affect and sedentary behavior in middle-aged women
Authors: Elavsky Steriani , Kishida Moé , Mogle Jacqueline A.
Published: June 2016

Objective:

The purpose of this study was to investigate the reciprocal relationship between sedentary behavior (SB) and momentary affect in the context of daily experiences.

Methods:

Community-dwelling midlife women (N = 121; age 40-60 y) were recruited for a 15-day daily diary study. The women rated their positive and negative affect when prompted on a personal digital assistant device four times per day and wore an accelerometer for objective assessment of SB. Multilevel models were estimated to test concurrent and lagged associations between momentary estimates of SB and affect.

Results:

In models that controlled for day of week, number of hot flashes, and total minutes of accelerometer wear time, greater concurrent positive affect was associated with fewer minutes spent being sedentary (β = −31, P < 0.01). Neither lagged positive nor negative affect predicted later SB; however, more sedentary minutes predicted lower positive affect at the next occasion (β = −0.04, P < 0.01).

Conclusions:

These results suggest that SB has negative affective consequences from moment to moment. The implications of reduced positive affect after prolonged bouts of SB for subsequent motivational, behavioral, or well-being outcomes remain to be determined.
Physical fitness improvement in overweight postmenopausal women who do not lose fat mass in response to exercise training
Authors: Myette-Côté Étienne , Archambault-Therrien Claudie , Brochu Martin , Dionne Isabelle J. , Riesco Eléonor
Published: June 2016

Objective:

The aim of this study was to examine if overweight postmenopausal women who do not experience fat mass loss after a 1-year aerobic exercise (AE) and resistance training (RT) program can still improve physical fitness.

Methods:

Thirty-one overweight women (body mass index 28-40 kg/m2 or waist circumference ≥88 cm) participated in three weekly supervised AE and RT sessions for 1 year. All women were categorized according to their fat mass changes after the intervention: 14 women were considered as responders (fat mass loss ≥5% of initial fat mass) and 17 as nonresponders (fat mass loss <5% of initial fat mass). The main outcome measures were absolute and relative body strength, peak aerobic capacity, lower limbs power, flexibility, and body composition (DXA). Total energy intake (3-day dietary record) and physical activity level (physical activity scale for the elderly questionnaire) were also measured before, halfway through and after the intervention.

Results:

At baseline, nonresponders participants had higher body mass index (P = 0.04). After the intervention, relative and absolute upper and lower body strength, peak aerobic capacity (all P < 0.005), and flexibility increased similarly in the nonresponders and responders groups (P = 0.01).

Conclusions:

Although some participants did not respond to exercise by decreasing fat mass, they still experienced important physical fitness benefits from AE and RT. These results suggest that body composition changes should not be the sole indicator of the benefits of exercise in overweight postmenopausal women.
The usability of a WeChat-based electronic questionnaire for collecting participant-reported data in female pelvic floor disorders: a comparison with the traditional paper-administered format
Authors: Sun Zhi-Jing , Zhu Lan , Liang Maolian , Xu Tao , Lang Jing-he
Published: June 2016

Objective:

WeChat is a promising tool for capturing electronic data; however, no research has examined its use. This study evaluates the reliability and feasibility of WeChat for administering the Pelvic Floor Impact Questionnaire Short Form 7 questionnaire to women with pelvic floor disorders.

Methods:

Sixty-eight pelvic floor rehabilitation women were recruited between June and December 2015 and crossover randomized to two groups. All participants completed two questionnaire formats. One group completed the paper version followed by the WeChat version; the other group completed the questionnaires in reverse order. Two weeks later, each group completed the two versions in reverse order. The WeChat version's reliability was assessed using intraclass correlation coefficients and test-retest reliability.

Results:

Forty-two women (61.8%) preferred the WeChat to the paper format, eight (11.8%) preferred the paper format, and 18 (26.5%) had no preference. The younger women preferred WeChat. Completion time was 116.5 (61.3) seconds for the WeChat version and 133.4 (107.0) seconds for the paper version, with no significant difference (P = 0.145). Age and education did not impact completion time (P > 0.05). Consistency between the WeChat and paper versions was excellent. The intraclass correlation coefficients of the Pelvic Floor Impact Questionnaire Short Form 7 and the three subscales ranged from 0.915 to 0.980. The Bland-Altman analysis and linear regression results also showed high consistency. The test-retest study had a Pearson's correlation coefficient of 0.908, demonstrating a strong correlation.

Conclusions:

WeChat-based questionnaires were well accepted by women with pelvic floor disorders and had good data quality and reliability.
Menopause is associated with articular cartilage degeneration: a clinical study of knee joint in 860 women
Authors: Lou Chao , Xiang Guangheng , Weng Qiaoyou , Chen Zhaojie , Chen Deheng , Wang Qingqing , Zhang Di , Zhou Bin , He Dengwei , Chen Hongliang
Published: June 2016

Objective:

The purpose of this study was to investigate the association between menopause and severity of knee joint cartilage degeneration using a magnetic resonance imaging-based six-level grading system, with six cartilage surfaces, the medial and lateral femoral condyle, the femoral trochlea, the medial and lateral tibia plateau, and the patella.

Methods:

The study cohort comprised 860 healthy women (age 36-83 y), and 5,160 cartilage surfaces were analyzed. Age, weight, height, age at natural menopause, and years since menopause (YSM) were obtained. Cartilage degeneration was assessed using a magnetic resonance imaging-based six-level grading system.

Results:

After removing the age, height, and weight effects, postmenopausal women had more severe cartilage degeneration than pre- and perimenopausal women (P < 0.001). A positive trend was observed between YSM and severity of cartilage degeneration (P < 0.05). Postmenopausal women were divided into seven subgroups by every five YSM. When YSM was less than 25 years, the analysis of covariance indicated a significant difference in medial tibia plateau, medial femoral condyle, trochlea, patella, and total surfaces (P < 0.05 or 0.01) between every two groups. When YSM was more than 25 years, the significant difference, however, disappeared in these four surfaces (P > 0.05). No significant difference was observed in lateral tibia plateau and lateral femoral condyle in postmenopausal women.

Conclusions:

Menopause is associated with cartilage degeneration of knee joint. After menopause, cartilage showed progressive severe degeneration that occurred in the first 25 YSM, suggesting estrogen deficiency might be a risk factor of cartilage degeneration of the knee joint. Further studies are needed to investigate whether age or menopause plays a more important role in the progression of cartilage degeneration in the knee joint.
STRANGULATION-INDUCED CENTRAL RETINAL ARTERY OCCLUSION: CASE REPORT AND REVIEW OF THE LITERATURE
Authors: Greven Margaret A. , Moshfeghi Darius M.
Published: June 2016

Purpose:

To describe a patient with central retinal artery occlusion following an episode of mechanical strangulation.

Methods:

A retrospective case report. An 83-year-old man presented with acute vision loss in his right eye after a strangling episode. Multimodal clinical imaging was performed.

Results:

Visual acuity in the affected right eye was no light perception. Examination revealed optic nerve edema and optic nerve pallor and also severe vascular attenuation and a cherry-red spot in the macula.

Conclusion:

Mechanical disruption of carotid plaque can lead to occlusion of the central retinal artery, which may portend a dismal visual prognosis.
Advances in Gamma Knife radiosurgery for pituitary tumors
Authors: Lee Cheng-Chia , Sheehan Jason P.
Published: June 2016

Purpose of review

For the residual/recurrent pituitary adenomas, stereotactic radiosurgery (SRS) plays an important role in long-term tumor control and, for secretory adenomas, endocrine remission. The purpose of this review is to address the advances in SRS technique and detail the latest treatment strategies for various types of pituitary adenomas with a focus on recently published literature.

Recent findings

From recent publications, SRS may be considered as an upfront treatment in patients with an adenoma that resides largely in the cavernous sinus and for whom resection is unlikely to produce substantial reduction in the overall tumor volume. Early treatment (<6 months after prior resection) with SRS appears to decrease the rate of tumor progression of subtotally resected nonfunctioning pituitary macroadenomas. Some types of adenomas may appear more aggressive with a high recurrence rate, for example, silent corticotroph pituitary adenomas, or sparsely granulated somatotroph-cell adenomas, may be indicated for a high-radiation dose. Finally, whole-sellar radiation and fractionated SRS are the alternative strategies, and may be indicated for challenging cases.

The role of SRS for the pituitary adenoma is well established, and the treatment strategy is increasingly individualized based upon tumor histology, location, and volume. Hypopituitarism is the most complicated and can occur even years after SRS.
Infliximab Optimization Based on Therapeutic Drug Monitoring in Pediatric Inflammatory Bowel Disease
Authors: Hofmekler Tatyana , Bertha Madeline , McCracken Courtney , Martineau Benadette , McKinnon Elizabeth , Schoen Bess T. , McElhanon Barbara O. , Tenjarla Gayathri , Kugathasan Subra , Sauer Cary G.
Published: June 2016

Background:

Infliximab (IFX) is an effective treatment for the management of moderate to severe inflammatory bowel disease (IBD). Low‐serum IFX levels are associated with the development of antibodies to IFX (ATI), which subsequently associated with clinical relapse and increased morbidity. The primary purpose of this study is to examine the relation between dose and interval to IFX level. Secondary goal is to evaluate the relation between IFX level and ATI in a pediatric IBD population.

Methods:

We performed a retrospective chart review of all children diagnosed with IBD and treated with IFX at a tertiary care pediatric IBD center. We performed our analysis based on prescribed dosing intervals and rounded dose up to 5 or 10 mg/kg as indicated in clinical practice.

Results:

Our study included 278 samples from 129 children on IFX. ATI were detected in 37 samples (13.3%). Low IFX levels (<3 μg/mL) were detected in 37.2% of children receiving IFX. Samples with ATI present had significantly lower levels of IFX than samples in which ATI were not present. For the dose 5 mg/kg, Q6 dosing had significantly higher IFX levels than Q8 dosing (P = 0.009). Higher IFX levels were seen with interval shortening rather than dose escalation.

Conclusions:

We demonstrate that low IFX levels are associated with development of immunogenicity to IFX as measured by ATI. We demonstrate that interval shortening rather than dose escalation results in higher IFX levels. We suggest that given the high number of IFX levels below 3 μg/mL in patients, early IFX level evaluation or primary initiation of Q6 week dosing be considered.
Gene Expression Profiles Suggest Iron Transport Pathway in the Lactating Human Epithelial Cell
Authors: Cai Chenxi , Eck Peter , Friel James K.
Published: June 2016

Objectives:

The molecular background of iron excretion into breast milk has not been determined in humans. We determined the expression of known iron transporters in mRNA extracted from human milk fat globules to deduce which known transporters are responsible for iron excretion into human milk.

Methods:

The expression of iron transporters in mRNA from human milk fat globules and mouse mammary epithelial cell lines was determined by quantitative real‐time polymerase chain reaction.

Results:

The expression of the transferrin receptor 1 (TFRC), divalent metal transporter 1 (SLC11A2), transferrin (TF), and lactoferrin (LTF) was confirmed in RNA isolated from the human milk fat globule. Similar expression was observed in the mouse mammary epithelial cell line HC11 in resting and lactating phenotypes. No iron export protein could be determined in the RNA isolated from fat globules in human breast milk and a human mammary epithelial cell line.

Conclusions:

The lack of iron exporters in the human mammary epithelia, in conjunction with the presence of lactoferrin suggests that transmembrane transport is not a major route of iron excretion into human milk.
Splanchnic Oxygenation at First Enteral Feeding in Preterm Infants
Authors: Corvaglia Luigi , Martini Silvia , Battistini Barbara , Rucci Paola , Faldella Giacomo , Aceti Arianna
Published: June 2016

Preterm infants are at risk of developing gastrointestinal complications such as feeding intolerance and necrotizing enterocolitis. Near‐infrared spectroscopy (NIRS) provides continuous monitoring of abdominal oxygenation (ArSO2) and could help to predict gastrointestinal complications in preterm neonates. In this prospective observational study, ArSO2 patterns at first enteral feed were evaluated by NIRS in 61 clinically stable preterm infants. Splanchnic‐cerebral oxygenation ratio, which is a marker of gut hypoxia, was also calculated. ArSO2 and splanchnic‐cerebral oxygenation ratio were significantly lower both at baseline and after feeding administration in infants who later developed feeding intolerance (n = 23). NIRS could help the early prediction of gastrointestinal complications in high‐risk preterm infants.
Creating Individualized Symptom Management Goals and Strategies for Cancer-Related Fatigue for Patients With Recurrent Ovarian Cancer
Authors: Hagan Teresa L. , Arida Janet A. , Hughes Susan H. , Donovan Heidi S.
Published: June 2016

Background:

Cancer-related fatigue (CRF) is one of the most common symptoms among women with recurrent ovarian cancer, yet it remains extremely difficult to manage. Symptom management typically requires patients to set goals and strategies to manage their CRF, but little is known about how to create individualized CRF symptom management goals and strategies.

Objective:

The aim of this study was to describe cancer patients’ goals and strategies for managing CRF along with their process of individualizing both.

Methods:

This study is a qualitative analysis with supportive quantitative description of a Web-based symptom management randomized clinical trial, the WRITE (Written Representational Intervention to Ease) Symptoms study. Researchers conducted a content analysis on 47 participants’ CRF symptom care plans to identify common themes in participants’ goals, categorize strategies, and describe the individualization process.

Results:

Four general themes were identified among participants’ CRF goals: (1) enjoying time with friends and family, (2) doing the things I enjoy, (3) having energy to be physically active, and (4) keeping up with what I need to do. Cancer-related fatigue strategies were categorized into 13 groups including conserving energy, increasing activity, and talking with healthcare providers. A multistep individualization process resulted in personally meaningful strategies.

Conclusions:

The process by which participants individualized their CRF strategies consisted of identifying, confirming, testing, and evaluating different CRF strategies and resulted in refined, specific, and individualized strategies intended to eventually ensure participants achieve their goal.

Implications for Practice:

Clinicians can assist patients in individualizing their CRF goals and strategies. Individualization of CRF goals and strategies assists patients in visualizing how improving CRF will impact their life.
Interventions for the Treatment of Aromatase Inhibitor–Associated Arthralgia in Breast Cancer Survivors
Authors: Yang Gee Su , Kim Hee Jun , Griffith Kathleen A. , Zhu Shijun , Dorsey Susan G. , Renn Cynthia L.
Published: June 2016

Background:

Aromatase inhibitors (AIs) have been established as successful adjuvant therapy for breast cancer survivors. Unfortunately, nearly half of women taking AIs report joint pain, AI-associated arthralgia (AIA). Aromatase inhibitor–associated arthralgia often results in noncompliance, which could lead to cancer recurrence.

Objective:

The purpose of this study was to identify current pain management of AIA and to evaluate the study quality and effects of interventions.

Methods:

Nineteen articles published from 2000 to August 2015 were identified using PubMed, CINAHL, PsycINFO, Web of Science, and additional records. Study quality was evaluated by the Quality Assessment Tool for Quantitative Studies. Meta-analysis was used to obtain effect sizes of interventions on pain and subgroups.

Results:

Five types of interventions emerged: pharmacological approaches, acupuncture, nutritional supplementation, relaxation techniques, and physical exercise. Six studies were strong, 8 were moderate, and 5 were weak in quality. The overall effect size of the interventions on pain was large; pharmacological approaches, acupuncture, and relaxation techniques showed moderate to large effects on pain, whereas nutritional supplementation and physical exercise had no significant effects on it.

Conclusion:

The evidence was based on a body of research with moderate study quality. Although the overall effect of interventions is large, further investigation into the influence of nutrition and physical exercise is needed to better discern their potential for pain management.

Implication for Practice:

Oncology nurses may be able to implement such validated interventions as pain management modalities to mitigate the symptoms so that breast cancer survivors remain compliant with AIA therapy.
Continuing Bonds and Bereavement Adjustment Among Bereaved Mainland Chinese
Authors: Yu Wei , He Li , Xu Wei , Wang Jianping , Prigerson Holly Gwen
Published: June 2016

Given the important role of continuing bonds (CBs) in bereavement adjustment, the aim of this study was to examine the relationship between CBs and bereavement adjustment and identify influences on CB among bereaved mainland Chinese. The Continuing Bonds Scale, Prolonged Grief Questionnaire 13, and Posttraumatic Growth Inventory were administered to 273 bereaved participants. Findings in the current study suggest psychometric validity of the Continuing Bonds Scale in a mainland Chinese sample and confirm that externalized CB is positively associated with severity of grief symptoms, and internalized CB is positively associated with the respondent degree of posttraumatic growth and identifies influences on externalized CB and internalized CB. These findings clarify the complex influence of CB in grieving process and highlight the need of incorporating CB into grief counseling.
Safety and Acceptability of the PrePex Device When Used in Routine Male Circumcision Service Delivery During Active Surveillance in Zimbabwe
Authors: Mavhu Webster , Hatzold Karin , Ncube Getrude , Xaba Sinokuthemba , Madidi Ngonidzashe , Keatinge Jo , Dhodho Efison , Samkange Christopher A. , Tshimanga Mufuta , Mangwiro Tonderayi , Mugurungi Owen , Njeuhmeli Emmanuel , Cowan Frances M.
Published: June 2016

Background:

Male circumcision devices have the potential to accelerate voluntary medical male circumcision roll-out, with PrePex being one promising device. Here, we present findings on safety and acceptability from active surveillance of the implementation of PrePex among 1000 males circumcised in Zimbabwe.

Methods:

The first 1000 men consecutively circumcised using PrePex during routine service delivery were actively followed up. Outcome measures included PrePex uptake, attendance for postcircumcision visits, and adverse events (AEs). A survey was conducted among 500 consecutive active surveillance clients to assess acceptability and satisfaction with PrePex.

Results:

A total of 2156 men aged 18 years or older were circumcised across the 6 PrePex active surveillance sites. Of these, 1000 (46.4%) were circumcised using PrePex. Among them, 4 (0.4%) self-removals that required surgery (severe AEs) were observed. Six (0.6%) removals by providers (moderate AEs) did not require surgery. A further 280 (28%) AEs were mild or moderate pain during device removal. There were also 12 (1.2%) moderate AEs unrelated to pain. All AEs resolved without sequelae. There was high adherence to follow-up appointments, with 97.7% of clients attending the scheduled day 7 visit. Acceptability of PrePex was high among survey participants, 93% indicated willingness to recommend the device to peers. Of note, 95.8% of respondents reported experiencing pain when the device was being removed. Additionally, 85.2% reported experiencing odor while wearing the device or during removal.

Conclusions:

Active surveillance of the first 1000 men circumcised using PrePex suggests that the device is both safe and acceptable when used in routine service delivery.
Factors Associated With Delayed Healing in a Study of the PrePex Device for Adult Male Circumcision in Kenya
Authors: Feldblum Paul J. , Odoyo-June Elijah , Bailey Robert C. , Jou Lai Jaim , Weiner Debra , Combes Stephanie , Hart Catherine , Fischer Shelly , Obiero Walter , Cherutich Peter
Published: June 2016

Objectives:

To explore factors associated with healing requiring more than 6 weeks after placement of the PrePex device for adult medical male circumcision.

Methods:

We enrolled 427 men ages 18–49 years in an observational study of PrePex at 1 urban and 2 peripheral clinics in western Kenya. Participants were scheduled for device removal at day 7 and a follow-up visit at day 42 (allowable range, 40–44) at which the provider recorded wound status, with complete healing defined as a dry wound without any scab, later confirmed by site investigator review of digital penile photographs. We performed univariate and multivariate logistic regression to explore associations between selected demographic, surgical, and follow-up factors and delayed healing (not healed by day 42 visit).

Results:

Of the 427 men, 341 completing a day 42 visit with physical examination and recorded healing status were included. Fifty-four percent of included men were healed by day 42 visit. Factors associated with delayed healing in univariate analysis and remaining significant in the multivariate analysis were as follows: age 25 years or older [odds ratio (OR): 1.8; 95% confidence interval (CI): 1.4 to 2.4], an adverse event by day 44 (OR: 1.4; 95% CI: 1.03 to 2.0), and severe pain during device removal (protective association: OR: 0.7; 95% CI: 0.5 to 0.99).

Conclusions:

Older age (25+ years), occurrence of an adverse event, and lesser self-reported pain at device removal were associated with delayed wound healing. If confirmed by larger surveillance studies, these results should be incorporated into the counseling given to male circumcision clients.
Innovative Methods of Male Circumcision for HIV Prevention—Getting the Right Evidence
Authors: Samuelson Julia , Hargreave Timothy , Ridzon Renee , Farley Tim
Published: June 2016

World Health Organization recommends that countries with hyperendemic and generalized HIV epidemics implement voluntary medical male circumcision programs for HIV prevention. Innovative methods of male circumcision including devices have the potential to simplify the procedure, reduce time and cost, increase client acceptability, enhance safety, and expand the numbers of providers who may perform circumcision. We describe work led by World Health Organization and supported by global partners to define a pathway for the evaluation of efficacy and safety of male circumcision devices, to set priority criteria, and to establish a process to guide the use of devices in publicly funded voluntary medical male circumcision programs for HIV prevention. A device classification scheme, an expert Technical Advisory Group on Innovations in Male Circumcision, and a formal prequalification program have also guided considerations on safe use of devices. A rigorous approach was deemed appropriate given the intervention is for use among healthy men for public health purposes. The pathway and processes led to coordinated research, better standardization in research outcomes, and guidance that informed the research, introduction and implementation phases. The lessons learnt from this case study can inform evaluation and use of future public health innovations.
Safety Profile of PrePex Male Circumcision Device and Client Satisfaction With Adolescent Males Aged 13–17 Years in Zimbabwe
Authors: Tshimanga Mafuta , Hatzold Karin , Mugurungi Owen , Mangwiro Tonderayi , Ncube Getrude , Xaba Sinokuthemba , Chatikobo Pesanai , Gundidza Patricia , Samkange Christopher , Dhlamini Roy , Murwira Munyaradzi , Gwinji Gerald
Published: June 2016

Background:

The safety and efficacy of the PrePex device for voluntary medical male circumcision (VMMC) has been demonstrated in studies in Rwanda, Uganda, and Zimbabwe, leading to the conditional prequalification of the device for use in adults. Because the majority of VMMC clients in the 14 priority countries are adolescents under 18 years, research to establish the safety and efficacy of the device for males <18 years is required.

Methods:

One-arm, prospective study included 402 adolescents, aged 13–17 years, using PrePex device between August 2013 and January 2014 at a VMMC centre in Harare. Endpoints are number and grade of adverse events associated with device circumcision, time to complete wound healing, client satisfaction with the procedure, and outcome.

Results:

The rate of medical ineligibility among adolescent males was high; 237/402 (35.9%) of study participants had to be excluded based on medical reasons. The severe/moderate adverse event rate was low at 2/402 (0.5%). No device displacements/self-removals were observed. Time to complete wound healing was shorter than in adults; 367/398 (92.2%) adolescents had completed wound healing by day 35, whereas 90% of adults had completed wound healing by day 56 as demonstrated in previous studies. Overall, adolescents were highly satisfied with the results of their circumcision.

Conclusions:

The study demonstrates that the PrePex device can be safely used in adolescents aged 13–17 years. The significant proportion of males opting for surgical circumcision and the high medical ineligibility suggest that surgical circumcision needs to be provided alongside PrePex services in programs targeting young age groups.
Brief Report: Pharmacokinetic/Pharmacodynamic Investigation of Single-Dose Oral Maraviroc in the Context of HIV-1 Pre-exposure Prophylaxis
Authors: Fox Julie , Tiraboschi Juan M. , Herrera Carolina , Else Laura , Egan Deirdre , Dickinson Laura , Jackson Akil , Olejniczak Natalia , Back David , Khoo Saye , Shattock Robin , Boffito Marta
Published: June 2016

To investigate the pharmacokinetics/pharmacodynamics of single-dose maraviroc 300 mg in HIV-1 exposure compartments. Maraviroc concentrations in blood, secretions (vaginal, urethral, oral, and rectal), and tissue (vaginal and rectal) were measured, and ex vivo challenge was performed in 54 healthy volunteers to study protection from HIV infection. Maraviroc Cmax occurred within 4 hours in most compartments. Concentrations from 4 to 72 hours were above intracellular (IC) IC90 in all compartments, range 15–8095 ng/mL. Mean AUC0-72 compartment-to-plasma ratios were highest in the rectum (45–819) and urethra (144) compared with the female genital tract (1.6–4.8) and saliva (0.2). No sex differences in AUC0-72 or Cmax were observed. No ex vivo protection from HIV-1BaL occurred in rectal or vaginal tissue. Despite high and sustained concentrations, single-dose maraviroc was not protective against ex vivo challenge of vaginal/rectal tissue.
Prosopagnosia as the Presenting Symptom of Whipple Disease
Authors: Tábuas-Pereira Miguel , Vicente Margarida , Coelho Filomena , Santana Isabel
Published: June 2016

Whipple disease is a rare, chronic multisystem infectious disease. The central nervous system (CNS) is secondarily involved in 43% of patients; 5% of patients have isolated or primary CNS involvement. The most frequent CNS symptoms are cognitive changes. Prosopagnosia is an inability to recognize familiar faces, in a person who does not have vision impairments or cognitive alterations. This relatively rare condition is usually related to vascular, traumatic, degenerative, or infectious lesions. We report a 54-year-old woman who presented subacutely with fever, headache, and seizures that led to a diagnosis of infectious meningoencephalitis. She improved temporarily on broad-spectrum antibiotics, but then developed a chronically evolving cognitive impairment with associative prosopagnosia as the major complaint. She had a history of sporadic abdominal pain and mild sacroiliac arthralgia. After a negative duodenal biopsy, we confirmed primary CNS Whipple disease by polymerase chain reaction and brain biopsy. We treated the patient with ceftriaxone for 15 days and then co-trimoxazole for 2 years. At 8-year follow-up, she had no further impairments, but continuing prosopagnosia. To our knowledge, this is the first description of isolated prosopagnosia in a patient with primary CNS Whipple disease. Because CNS Whipple disease can lead to serious, irreversible lesions if not promptly treated, clinicians must suspect the diagnosis, treat with long-term antibiotics, and follow patients carefully to prevent recurrence.
Patterns of species range evolution in Indo-Pacific reef assemblages reveal the Coral Triangle as a net source of transoceanic diversity
Authors: Evans Sean M. , McKenna Caroline , Simpson Stephen D. , Tournois Jennifer , Genner Martin J.
Published: June 2016

The Coral Triangle in the Indo-Pacific is a region renowned for exceptional marine biodiversity. The area could have acted as a ‘centre of origin’ where speciation has been prolific or a ‘centre of survival’ by providing refuge during major environmental shifts such as sea-level changes. The region could also have acted as a ‘centre of accumulation’ for species with origins outside of the Coral Triangle, owing to it being at a central position between the Indian and Pacific oceans. Here, we investigated support for these hypotheses using population-level DNA sequence-based reconstructions of the range evolution of 45 species (314 populations) of Indo-Pacific reef-associated organisms. Our results show that populations undergoing the most ancient establishment were significantly more likely to be closer to the centre of the Coral Triangle than to peripheral locations. The data are consistent with the Coral Triangle being a net source of coral-reef biodiversity for the Indo-Pacific region, suggesting that the region has acted primarily as a centre of survival, a centre of origin or both. These results provide evidence of how a key location can influence the large-scale distributions of biodiversity over evolutionary timescales.
Physiological niche and geographical range in European diving beetles (Coleoptera: Dytiscidae)
Authors: Cioffi Rebekah , Moody A. John , Millán Andrés , Billington Richard A. , Bilton David T.
Published: June 2016

Geographical ranges vary greatly in size and position, even within recent clades, but the factors driving this remain poorly understood. In aquatic beetles, thermal niche has been shown to be related to both the relative range size and position of congeners but whether other physiological parameters play a role is unknown. Metabolic plasticity may be critical for species occupying more variable thermal environments and maintaining this plasticity may trade-off against other physiological processes such as immunocompetence. Here we combine data on thermal physiology with measures of metabolic plasticity and immunocompetence to explore these relationships inDeronectes(Dytiscidae). While variation in latitudinal range extent and position was explained in part by thermal physiology, aspects of metabolic plasticity and immunocompetence also appeared important. Northerly distributed, wide-ranging species apparently used different energy reserves under thermal stress from southern endemic congeners and differed in their antibacterial defences. This is the first indication that these processes may be related to geographical range, and suggests parameters that may be worthy of exploration in other taxa.
Effects of protein malnutrition on tolerance to helminth infection
Authors: Clough Dagmar , Prykhodko Olena , Råberg Lars
Published: June 2016

Infection tolerance is the ability of a host to limit the health effects of a given parasite load. A few recent studies have demonstrated genetic variation for tolerance, but little is known about how environmental factors affect tolerance. Here, we used the intestinal nematode
Heligmosomoides polygyrus
in laboratory mice to test for effects of protein malnutrition on tolerance
.
We performed an experiment where two different mouse strains (CBA and BALB/c) were fed either adequate-protein food or low-protein food, and trickle-infected with different doses of
H. polygyrus
larvae during four weeks. We found that protein malnutrition decreases tolerance measured as intestinal barrier function, but only in one of the strains (BALB/c); that is, there was a host genotype-by-environment interaction for tolerance. We conclude that nutritional status can affect tolerance and that sensitivity of tolerance to malnutrition may differ between host genotypes.
Budgerigar flight in a varying environment: flight at distinct speeds?
Authors: Schiffner Ingo , Srinivasan Mandyam V.
Published: June 2016

How do flying birds respond to changing environments? The behaviour of budgerigars,Melopsittacus undulatus, was filmed as they flew through a tapered tunnel. Unlike flying insects—which vary their speed progressively and continuously by holding constant the optic flow induced by the walls—the birds showed a tendency to fly at only two distinct, fixed speeds. They switched between a high speed in the wider section of the tunnel, and a low speed in the narrower section. The transition between the two speeds was abrupt, and anticipatory. The high speed was close to the energy-efficient, outdoor cruising speed for these birds, while the low speed was approximately half this value. This is the first observation of the existence of two distinct, preferred flight speeds in birds. A dual-speed flight strategy may be beneficial for birds that fly in varying environments, with the high speed set at an energy-efficient value for flight through open spaces, and the low speed suited to safe manoeuvring in a cluttered environment. The constancy of flight speed within each regime enables the distances of obstacles and landmarks to be directly calibrated in terms of optic flow, thus facilitating simple and efficient guidance of flight through changing environments.
The cost of prospecting for dispersal opportunities in a social bird
Authors: Kingma Sjouke A. , Komdeur Jan , Hammers Martijn , Richardson David S.
Published: June 2016

Understanding why individuals delay dispersal and become subordinates within a group is central to studying the evolution of sociality. Hypotheses predict that dispersal decisions are influenced by costs of extra-territorial prospecting that are often required to find a breeding vacancy. Little is known about such costs, partly because it is complicated to demonstrate them empirically. For example, prospecting individuals may be of inferior quality already before prospecting and/or have been evicted. Moreover, costs of prospecting are mainly studied in species where prospectors suffer from predation risk, so how costly prospecting is when predators are absent remains unclear. Here, we determine a cost of prospecting for subordinate Seychelles warblers,Acrocephalus sechellensis, in a population where predators are absent and individuals return to their resident territory after prospecting. Prospecting individuals had 5.2% lower body mass than non-prospecting individuals. Our evidence suggests this may be owing to frequent attacks by resident conspecifics, likely leading to reduced food intake by prospectors. These results support the hypothesis that energetic costs associated with dispersal opportunities are one factor influencing dispersal decisions and shaping the evolution of delayed dispersal in social animals.
Techniques to assess bone ultrastructure organization: orientation and arrangement of mineralized collagen fibrils
Authors: Georgiadis Marios , Müller Ralph , Schneider Philipp
Published: June 2016

Bone's remarkable mechanical properties are a result of its hierarchical structure. The mineralized collagen fibrils, made up of collagen fibrils and crystal platelets, are bone's building blocks at an ultrastructural level. The organization of bone's ultrastructure with respect to the orientation and arrangement of mineralized collagen fibrils has been the matter of numerous studies based on a variety of imaging techniques in the past decades. These techniques either exploit physical principles, such as polarization, diffraction or scattering to examine bone ultrastructure orientation and arrangement, or directly image the fibrils at the sub-micrometre scale. They make use of diverse probes such as visible light, X-rays and electrons at different scales, from centimetres down to nanometres. They allow imaging of bone sections or surfaces in two dimensions or investigating bone tissue truly in three dimensions,
in vivo
or
ex vivo
, and sometimes in combination with
in situ
mechanical experiments. The purpose of this review is to summarize and discuss this broad range of imaging techniques and the different modalities of their use, in order to discuss their advantages and limitations for the assessment of bone ultrastructure organization with respect to the orientation and arrangement of mineralized collagen fibrils.
Systematic tracking of altered haematopoiesis during sporozoite-mediated malaria development reveals multiple response points
Authors: Vainieri Maria L. , Blagborough Andrew M. , MacLean Adam L. , Haltalli Myriam L. R. , Ruivo Nicola , Fletcher Helen A. , Stumpf Michael P. H. , Sinden Robert E. , Lo Celso Cristina
Published: June 2016

Haematopoiesis is the complex developmental process that maintains the turnover of all blood cell lineages. It critically depends on the correct functioning of rare, quiescent haematopoietic stem cells (HSCs) and more numerous, HSC-derived, highly proliferative and differentiating haematopoietic progenitor cells (HPCs). Infection is known to affect HSCs, with severe and chronic inflammatory stimuli leading to stem cell pool depletion, while acute, non-lethal infections exert transient and even potentiating effects. Both whether this paradigm applies to all infections and whether the HSC response is the dominant driver of the changes observed during stressed haematopoiesis remain open questions. We use a mouse model of malaria, based on natural, sporozoite-driven
Plasmodium berghei
infection, as an experimental platform to gain a global view of haematopoietic perturbations during infection progression. We observe coordinated responses by the most primitive HSCs and multiple HPCs, some starting before blood parasitaemia is detected. We show that, despite highly variable inter-host responses, primitive HSCs become highly proliferative, but mathematical modelling suggests that this alone is not sufficient to significantly impact the whole haematopoietic cascade. We observe that the dramatic expansion of Sca-1
+
progenitors results from combined proliferation of direct HSC progeny and phenotypic changes in downstream populations. We observe that the simultaneous perturbation of HSC/HPC population dynamics is coupled with early signs of anaemia onset. Our data uncover a complex relationship between
Plasmodium
and its host's haematopoiesis and raise the question whether the variable responses observed may affect the outcome of the infection itself and its long-term consequences on the host.
Mass spectrometry-guided refinement of chemical energy buffers
Authors: Chen T.-R. , Urban P. L.
Published: June 2016

Biocatalytic reactions often require supplying chemical energy and phosphate groups in the form of adenosine triphosphate (ATP). Auxiliary enzymes can be used to convert a reaction by-product—adenosine diphosphate (ADP)—back to ATP. By employing real-time mass spectrometry (RTMS), one can gain an insight into inter-conversions of reactants in multi-enzyme reaction systems and optimize the reaction conditions. In this study, temporal traces of ions corresponding to adenosine monophosphate (AMP), ADP and ATP provided vital information that could be used to adjust activities of the ‘buffering enzymes’. Using the RTMS results as a feedback, we also characterized a bienzymatic energy buffer that enables the recovery of ATP in the cases where it is directly hydrolysed to AMP in the main enzymatic reaction. The significance of careful selection of enzyme activities—guided by RTMS—is exemplified in the synthesis of glucose-6-phosphate by hexokinase in the presence of a buffering enzyme, pyruvate kinase. Relative activities of the two enzymes, present in the reaction mixture, influence biosynthetic reaction yields. This observation supports the conclusion that optimization of chemical energy recycling procedures is critical for the biosynthetic reaction economy.
Formation mechanism of a basin of attraction for passive dynamic walking induced by intrinsic hyperbolicity
Authors: Obayashi Ippei , Aoi Shinya , Tsuchiya Kazuo , Kokubu Hiroshi
Published: June 2016

Passive dynamic walking is a useful model for investigating the mechanical functions of the body that produce energy-efficient walking. The basin of attraction is very small and thin, and it has a fractal-like shape; this explains the difficulty in producing stable passive dynamic walking. The underlying mechanism that produces these geometric characteristics was not known. In this paper, we consider this from the viewpoint of dynamical systems theory, and we use the simplest walking model to clarify the mechanism that forms the basin of attraction for passive dynamic walking. We show that the intrinsic saddle-type hyperbolicity of the upright equilibrium point in the governing dynamics plays an important role in the geometrical characteristics of the basin of attraction; this contributes to our understanding of the stability mechanism of bipedal walking.
Asymmetric shape transitions of epitaxial quantum dots
Authors: Wei Chaozhen , Spencer Brian J.
Published: June 2016

We construct a two-dimensional continuum model to describe the energetics of shape transitions in fully faceted epitaxial quantum dots (strained islands) via minimization of elastic energy and surface energy at fixed volume. The elastic energy of the island is based on a third-order approximation, enabling us to consider shape transitions between pyramids, domes, multifaceted domes and asymmetric intermediate states. The energetics of the shape transitions are determined by numerically calculating the facet lengths that minimize the energy of a given island type of prescribed island volume. By comparing the energy of different island types with the same volume and analysing the energy surface as a function of the island shape parameters, we determine the bifurcation diagram of equilibrium solutions and their stability, as well as the lowest barrier transition pathway for the island shape as a function of increasing volume. The main result is that the shape transition from pyramid to dome to multifaceted dome occurs through sequential nucleation of facets and involves asymmetric metastable transition shapes. We also explicitly determine the effect of corner energy (facet edge energy) on shape transitions and interpret the results in terms of the relative stability of asymmetric island shapes as observed in experiment.
Human shields mediate sexual conflict in a top predator
Authors: Steyaert S. M. J. G. , Leclerc M. , Pelletier F. , Kindberg J. , Brunberg S. , Swenson J. E. , Zedrosser A.
Published: June 2016

Selecting the right habitat in a risky landscape is crucial for an individual's survival and reproduction. In predator–prey systems, prey often can anticipate the habitat use of their main predator and may use protective associates (i.e. typically an apex predator) as shields against predation. Although never tested, such mechanisms should also evolve in systems in which sexual conflict affects offspring survival. Here, we assessed the relationship between offspring survival and habitat selection, as well as the use of protective associates, in a system in which sexually selected infanticide (SSI), rather than interspecific predation, affects offspring survival. We used the Scandinavian brown bear (
Ursus arctos
) population with SSI in a human-dominated landscape as our model system. Bears, especially adult males, generally avoid humans in our study system. We used resource selection functions to contrast habitat selection of GPS-collared mothers that were successful (i.e. surviving litters,
n
= 19) and unsuccessful (i.e. complete litter loss,
n
= 11) in keeping their young during the mating season (2005–2012). Habitat selection was indeed a predictor of litter survival. Successful mothers were more likely to use humans as protective associates, whereas unsuccessful mothers avoided humans. Our results suggest that principles of predator–prey and fear ecology theory (e.g. non-consumptive and cascading effects) can also be applied to the context of sexual conflict.