bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel methods for nucleotide length control in double-stranded polyinosinic-polycytidylic acid production using uneven length components
Authors: Nakano Tetsuo , Yamamura Ei-Tora , Fujita Hiroshi , Sone Teruo , Asano Kozo
Published: August 2018

Polyinosinic-polycytidylic acid (PIC), a double-stranded RNA that induces innate immunity in mammals, is a candidate immunopotentiator for pharmaceuticals. The potency and adverse effects of PIC are strongly correlated with the nucleotide length, and the inability to precisely control the length in PIC production limits its practical use. Length extension during the annealing process is the major factor underlying the lack of control, but tuning the annealing conditions is insufficient to resolve this issue. In this study, we developed a novel method to produce accurate nucleotide length PIC at an industrial scale. The length extension was significantly suppressed by the assembly of multiple short polyinosinic acid molecules with one long polycytidylic acid molecule. A newly developed PIC, uPIC100-400, demonstrated a reproducible length and better storage stability than that of corresponding evenly structured PIC. Human dsRNA receptors exhibited equivalent responsiveness to uPIC100-400 and the evenly structured PIC with the same length.
Seizure response to temozolomide chemotherapy in patients with WHO grade II oligodendroglioma: a single-institution descriptive study
Authors: Haggiagi Aya , Avila Edward K
Published: August 2018

Background

Tumor-related epilepsy (TRE) is common in patients with low-grade oligodendrogliomas. TRE is difficult to control despite multiple antiepileptic drugs (AEDs) in up to 30% of patients. Chemotherapy has been used for treatment to avoid potential radiotherapy-related neurotoxicity. This study evaluates the effect of temozolomide on seizure frequency in a homogeneous group with World Health Organization (WHO) grade II oligodendrogliomas.

Methods

A retrospective analysis was conducted of adult patients with WHO grade II oligodendrogliomas and TRE followed at Memorial Sloan Kettering between 2005 and 2015 who were treated with temozolomide alone either as initial treatment or for disease progression. All had seizures 3 months prior to starting temozolomide. Seizure frequency was reviewed every 2 cycles and at the end of temozolomide treatment. Seizure reduction of ≥50% compared to baseline was defined as improvement.

Results

Thirty-nine individuals met inclusion criteria. Median follow-up since starting temozolomide was 6 years (0.8-13 years). Reduction in seizure frequency occurred in 35 patients (89.7%). Improvement was independent of AED regimen adjustments or prior antitumor treatment in 16 (41%); of these, AED dosage was successfully reduced or completely eliminated in 10 (25.6%). Twenty-five patients (64.1%) remained on a stable AED regimen. The majority (n = 32, 82%) had radiographically stable disease, 5 (12.8%) had objective radiographic response, and 2 (5.2%) had disease progression.

Conclusions

Temozolomide may result in reduced seizure frequency, and permit discontinuation of AEDs in patients with WHO II oligodendroglioma. Improvement was observed irrespective of objective tumor response on MRI, emphasizing the importance of incorporating seizure control in assessing response to tumor-directed therapy.
Outpatient Parenteral Antimicrobial Therapy Among People Who Inject Drugs: A Review of the Literature
Authors: Suzuki Joji , Johnson Jennifer , Montgomery Mary , Hayden Margaret , Price Christin
Published: August 2018

Hospitalizations for people who inject drugs (PWID) with infectious complications requiring prolonged antibiotic therapy are increasing in the context of the opioid epidemic. Although outpatient parenteral antimicrobial therapy (OPAT) is routinely offered to patients without a history of injection drug use (IDU), PWID are often excluded from consideration of OPAT. To better assess the evidence base for the safety and effectiveness of OPAT for PWID, we conducted a review of the published literature. Results suggest that OPAT may be safe and effective for PWID, with rates of OPAT completion, mortality, and catheter-related complications comparable to rates among patients without a history of IDU. Rates of hospital readmissions may be higher among PWID, but instances of misuse of the venous catheter were rarely reported. More research is needed to study the safety and effectiveness of OPAT among PWID, as well as studying the combination of OPAT and addiction treatment.
On surface brightness and flux calibration for point and compact extended sources in the AKARI Far-IR All-Sky Survey (AFASS) maps
Authors: Ueta Toshiya , Szczerba Ryszard , Fullard Andrew G , Takita Satoshi
Published: August 2018

The AKARI infrared astronomical satellite produced all-sky survey (AFASS) maps in the far-infrared at roughly arcminute spatial resolution, enabling us to investigate the whole sky in the far-infrared for objects having surface brightnesses greater than a few to a couple of dozen MJy sr−1. While the AFASS maps are absolutely calibrated against large-scale diffuse emission, it was uncertain whether or not an additional flux correction for point sources was necessary. Here, we verify that calibration for point-source photometry in the AFASS maps is proper. With the aperture correction method based on the empirical point spread function templates derived directly from the AFASS maps, fluxes in the AKARI bright source catalogue (BSC) are reproduced. The AKARI BSC fluxes are also satisfactorily recovered with the 1 σ aperture, which is the empirical equivalent of an infinite aperture. These results confirm that in the AFASS maps far-infrared photometry can be properly performed by using the aperture correction method for point sources and by summing all pixel values within an appropriately defined aperture of the intended target (i.e., the aperture photometry method) for extended sources.
Interaction between plasma homocysteine and the MTHFR C.677C > T polymorphism is associated with site‐specific changes in DNA methylation in humans
Authors: Nash Alexander J. , Mandaviya Pooja R. , Dib Marie-Joe , Uitterlinden André G. , van Meurs Joyce , Heil Sandra G. , Andrew Toby , Ahmadi Kourosh R.
Published: August 2018

One‐carbon metabolism provides a direct link among dietary folate/vitamin B12 exposure, the activity of the enzyme methylenetetrahydrofolate reductase (MTHFR), and epigenetic regulation of the genome via DNA methylation. Previously, it has been shown that the common C.677C > T polymorphism in MTHFR influences global DNA methylation status through a direct interaction with folate status and (indirectly) with total homocysteine (tHcy) levels. To build on that and other more recent observations that have further highlighted associations among MTHFR C.677C > T, tHcy, and aberrations in DNA methylation, we investigated whether the interaction between mildly elevated plasma tHcy and the C.677C > T polymorphism is associated with site‐specific changes in DNA methylation in humans. We used data on plasma tHcy levels, c.677C> T polymorphism, and site‐specific DNA methylation levels for a total of 915 white women and 335 men from the TwinsUK registry (n = 610) and the Rotterdam study (n = 670). We performed methylome‐wide association analyses in each cohort to model the interaction between levels of tHcy and C.677C > T genotypes on DNA methylation β values. Our meta‐analysis identified 13 probes significantly associated with rs1801133 × tHcy levels [false‐discovery rate (FDR) < 0.05]. The most significant associations were with a cluster of probes at the AGTRAP–MTHFR–NPPA/B gene locus on chromosome 1 (FDR = 1.3E–04), with additional probes on chromosomes 2, 3, 4, 7, 12, 16, and 19. Our top 2 hits on chromosome 1 were functionally associated with variability in expression of the TNF receptor superfamily member 8 (TNFRSF8) gene/locus on that chromosome. This is the first study, to our knowledge, to provide a direct link between perturbations in 1‐carbon metabolism, through an interaction of tHcy and the activity of MTHFR enzyme on epigenetic regulation of the genome via DNA methylation.—Nash, A. J., Mandaviya, P. R., Dib, M.‐J., Uitterlinden, A. G., van Meurs, J., Heil, S. G., Andrew, T., Ahmadi, K. R. Interaction between plasma homocysteine and the MTHFR c.677C>T polymorphism is associated with site‐specific changes in DNA methylation in humans. FASEB J. 33, 833–843 (2019). www.fasebj.org
Role of Preexposure Prophylaxis in the Reproductive Health of Women at Risk for Human Immunodeficiency Virus Infection
Authors: Pollock Lealah , Levison Judy
Published: August 2018

Women in the United States and especially women of color continue to acquire human immunodeficiency virus (HIV) infection. During reproductive health visits, health care providers are ideally positioned to assess HIV risk and offer HIV prevention strategies, including preexposure prophylaxis (also known as “PrEP”), a once-daily fixed-dose combination of emtricitabine with tenofovir disoproxil fumarate approved by the U.S. Food and Drug Administration for use to prevent HIV acquisition in persons at risk. Family planning, pregnancy, and postpartum visits provide an opportunity to ask sensitive questions about sexual and reproductive health and to help women navigate preference-sensitive decisions, including an individualized plan for HIV prevention. Exposure to a fixed-dose combination of emtricitabine with tenofovir disoproxil fumarate during pregnancy and breastfeeding appears to be safe with respect to maternal and infant outcomes. This article reviews the critical issues, challenges, and opportunities when implementing preexposure prophylaxis for women at risk for HIV who are seeking family planning services or pregnancy or postpartum care.
How to Prevent K-Wire Bounce in Oblique Supracondylar Humerus Fractures
Authors: Iobst Christopher , Thompson R. Gil , Grauer Jordan , Wheeler Peter
Published: August 2018

Supracondylar humerus fractures with an obliquely oriented fracture pattern can pose a clinical challenge in obtaining adequate fixation. Traditionally, 1.6-mm Kirchner wires are used for fracture fixation when pinning pediatric supracondylar humerus fractures. However, when pinning across obliquely oriented fractures, the angle of pin inclination may increase to the point where the 1.6-mm k-wire cannot penetrate the far cortex. We have found that, when pinning oblique supracondylar humerus fractures, utilization of a 2.0-mm k-wire can assist the surgeon in obtaining bicortical purchase. We present a cadaveric study demonstrating the maximal angles at which both 1.6-mm and 2.0-mm k-wires will penetrate the far cortex. This technical trick can give surgeons a relatively simple solution to treat these difficult fractures.
Pulseless Supracondylar Humerus Fracture With Anterior Interosseous Nerve or Median Nerve Injury—An Absolute Indication for Open Reduction?
Authors: Harris Liam R. , Arkader Alexandre , Broom Alexander , Flynn John , Yellin Joseph , Whitlock Patrick , Miller Ashley , Sawyer Jeffrey , Roaten John , Skaggs David L. , Choi Paul D.
Published: August 2018

Background:

Optimal management for a pulseless supracondylar humerus fracture associated with anterior interosseous nerve (AIN) or median nerve injury is unclear. The purpose of this study was to determine the incidence of pulseless supracondylar humerus fractures associated with AIN or median nerve injury, to assess open versus closed surgical management, to determine factors associated with the need for neurovascular intervention, and to report the outcome.

Methods:

A retrospective review was performed at 4 pediatric trauma hospitals on all patients who sustained a Gartland III or IV supracondylar humerus fracture with the combination of absent distal palpable pulses and AIN or median nerve injury between 2000 and 2014. Choice of treatment, details regarding preoperative and postoperative exam findings, follow-up course, and outcome were recorded.

Results:

A total of 71 patients met inclusion criteria; 52 patients (73%) underwent closed reduction (CR); 19 patients (27%) underwent open reduction (OR) and early antecubital fossa exploration. The index procedure of CR plus percutaneous pinning was sufficient treatment in 50 (of 52, 96%) patients with only 2 requiring reoperation. One patient developed compartment syndrome approximately 9 hours after CRPP (13.5 h after time of injury) and underwent emergent fasciotomies. Of the 19 patients who underwent OR and early exploration, 6 needed vascular procedures, 5 required detethering of entrapped surrounding fibrous tissues. Forty patients were diagnosed with median nerve palsy versus 31 diagnosed with AIN palsy. There was no significant difference between patients presenting with median nerve versus AIN palsy, with similar rates of need for OR (10/40; 25% vs. 9/31; 29%), rate of compartment syndrome (3/40; 7.5% vs. 3/31; 9.7%), need for reoperation (4/40; 10% vs. 6.5%), and ultimate resolution of nerve palsy (4/36; 20.1% vs. 3/30; 10%). Compartment syndrome developed in 6 (of 71, 8.5%) patients and was associated with poor perfusion status on presentation and delayed time from injury to surgery. In patients with at least 3-month neurological follow-up, 59 (of 61, 97%) patients had complete resolution of nerve palsy.

Conclusions:

Although previous authors have suggested a pulseless SCH fx with an associated AIN or median nerve injury should be treated with exploration and OR, 70% (50/71) of the patients in this series were treated with a CR. In this series, both AIN and median nerve palsies among patients presenting with pulseless extremity and Gartland III or IV SCH fracture, offer similar rates of OR, risk of compartment syndrome, and resolution of nerve palsy.

Level of Evidence:

Level IV.
Use of Dorsal Skin Islands as Firebreak Grafts to the Palm to Reduce the Recurrence Rate of Dupuytren’s Contracture
Authors: Kakinoki Ryosuke , Ohtani Kazuhiro , Hashimoto Kazuhiko , Tanaka Hiroki , Ikeguchi Ryosuke , Ohta Souichi , Akagi Masao
Published: August 2018

Dupuytren’s pathologic tissue usually involves the palmar skin and rarely infiltrates into the dorsal skin. In this study, we hypothesized that transplantation of a vascularized cutaneous flap harvested from the dorsum of the hand to the palmar skin, under which the pathologic cord existed might be useful for blocking reformation of the pathologic cords and for decreasing the recurrence rate. After removal of the pathologic tissue under the palmar skin, we harvested 2 types of skin islands nourished by the dorsal digital arterial network including the dorsal perforating arteries arising from the palmar digital arteries. The skin islands were transplanted into skin defects in the palm of the fingers and hand that had been created after correction of flexion contracture of the fingers. We performed this surgical maneuver on 24 fingers in 24 patients who exhibited severe flexion contracture because of Dupuytren disease. During the mean 40-month follow-up, only 1 patient experienced metacarpophalangeal joint flexion contracture ≥20 degrees in the operated finger. The recurrence rate was 4.2%, which was almost similar to that for a dermofasciectomy followed by a large full-thickness skin graft.
Risk Factors Associated With Pouch Adenomas in Patients With Familial Adenomatous Polyposis
Authors: Ganschow Petra , Trauth Silke , Hinz Ulf , Schaible Anja , Büchler Markus W. , Kadmon Martina
Published: August 2018

BACKGROUND:

Restorative proctocolectomy with ileal pouch-anal reconstruction is the standard prophylactic surgical procedure for patients with familial adenomatous polyposis. However, several groups have reported the development of adenomas and even carcinomas within the ileal pouch. The predisposing factor was the time interval after pouch surgery in some studies, but it was the severity of the initial colonic disease and duodenal adenomatosis in others.

OBJECTIVE:

The aim of this study was to further clarify the prevalence of pouch adenomas, clinical risk factors, and a possible phenotype–genotype relation in a large population of patients with familial adenomatous polyposis, as well as to analyze pouch adenoma-free survival.

DESIGN:

This study was designed as a cohort study.

SETTINGS:

This study was conducted in a specialized outpatient clinic at the University of Heidelberg.

PATIENTS:

A total of 192 patients with familial adenomatous polyposis were included, and all of the available endoscopy reports after pouch surgery were screened for pouch adenomas. Additional clinical information was retrieved from the Heidelberg Polyposis Register.

MAIN OUTCOME MEASURES:

This present study revealed 3 main independent risk factors for the development of pouch adenomas: age <18 years at the time of IPAA, male sex, and the presence of gastric adenomas. Secondary outcome measures were adenoma progression and overall pouch adenoma-free survival.

RESULTS:

Pouch adenomas were detected in 46.9% of patients. Median follow-up was 12.8 years (interquartile range, 9.0–17.0 y) for patients with pouch adenomas and 7.3 years (interquartile range, 2.5–12.2 y) for those without them. Patients underwent pouch surgery at a median age of 27.5 years (range, 10.2–58.5 y), and pouch adenomas occurred a median of 8.5 years (range, 0.9–25.1 y) after surgery. Also detected were gastric adenomas in 37.2%, duodenal adenomas in 80.3%, and desmoid tumors in 24.5% of patients. Estimation of pouch adenoma-free survival revealed that, after 20 years, only ≈22% of patients would be free of pouch adenomas. Male sex, age ≦18 years at the time of pouch surgery, and gastric adenomas were found to be independent risk factors for the development of pouch adenomas in a multivariate Cox regression analysis (p = 0.0002, p = 0.0059, and p = 0.0020). No predisposing germline mutation for pouch adenoma development was detected.

LIMITATIONS:

Detailed information on the initial preoperative findings was not fully available, and the study was only carried out as a single-center study.

CONCLUSIONS:

A severe upper intestinal phenotype, male sex, and age <18 years at the time of IPAA all increase the risk for development of pouch adenomas. See Video Abstract at http://links.lww.com/DCR/A675.
Video Super-microsurgery Amplified using Close-up Lens Filter on the Operative Field Camera: Preliminary Report
Authors: Kato Motoi , Watanabe Shoji , Watanabe Azusa , Utsunomiya Hiroki , Yokoyama Takayuki , Watanabe Taro
Published: August 2018

Background:

Super-microsurgery has widely spread due to the improvement of high magnification microscopes. The cost of multiple microscopes is high. Furthermore, the microscope heads are too large to fit in multiple surgical fields for pediatric patients. We adapted a 2-dimensional magnification system for performing lymphatic venous anastomosis on pediatric lymphedema cases.

Methods:

We attached a close-up lens filter to the suspended camera (CHZ-1,360-PTR camera, Carina system, Tokyo, Japan) in the operative field. This was done to achieve 26× magnification using a small camera head, making it possible to perform super-micro anastomoses. Anastomoses time, scar length, and lymph vessel diameters were measured, and the outcomes were statistically analyzed and compared with the contralateral side.

Results:

Four pediatric lymphedema patients underwent the aforementioned technique, using the multisite microscopic approach. All anastomoses were completed within 20 minutes. The results were not significantly different from the conventional microscopic lymphatic venous anastomosis.

Conclusion:

This system is advantageous because (1) it has less costly initial investments; (2) it requires a small camera head, which provides available space for the multisite microscopic approach even for pediatric patients; and (3) it allows for a wider surgical working space.
An Overlooked but Effective Wound Care Methodology: Hydromechanical Therapy Revisited
Authors: Desjardins Haley , Guo Lifei
Published: August 2018

Chronic wounds are frequently difficult, expensive to treat, and pose a significant burden on both the patient’s quality of life and health care system. Their recalcitrance to treatment stems from multiple factors, particularly the presence of bacterial biofilms within the wound bed. However, a commonly overlooked modality in the field of wound care, pressurized irrigation, offers an inexpensive mechanical debridement force capable of dislodging these biofilms that contribute to delayed healing of chronic wounds. We present here a single clinical case of a difficult nonhealing wound that had previously failed 3 months of negative-pressure wound therapy, a much more expensive modality. This chronic plantar foot wound was treated with daily application of hydromechanical therapy using tap water at home. It achieved a stable granulation surface, and with a small skin graft, healing with no recurrence seen at 15-month follow-up. We speculate that a combination of tissue stimulation and disruption of the wound surface biofilm contribute to improved healing, supporting a reevaluation for the use of pressurized irrigation in the treatment of chronic wounds.
The impact of accountable care organization participation on hospital patient experience
Authors: Diana Mark L. , Zhang Yongkang , Yeager Valerie A. , Stoecker Charles , Counts Catherine R.
Published: August 2018

Background:

Accountable care organizations (ACOs) are being implemented rapidly across the Unites States. Previous studies indicated an increasing number of hospitals have participated in ACOs. However, little is known about how ACO participation could influence hospitals’ performance.

Purpose:

This study aims to examine the impact of Medicare ACO participation on hospitals’ patient experience.

Methodology/Approach:

Difference-in-difference analyses were conducted to compare 10 patient experience measures between hospitals participating in Medicare ACOs and those not participating.

Results:

In general, hospitals participating in Pioneer ACOs had significantly improved scores on nursing communication and doctor communication. Shared Savings Program (SSP) ACO participation did not show significant improvement of patient experience. Subgroup analyses indicate that, for hospitals in the middle and top tertile groups in terms of baseline experience, Pioneer ACO and SSP ACO participation was associated with better patient experience. For hospitals in the bottom tertile, Pioneer ACO and SSP ACO participation had no association with patient experience.

Conclusion:

ACO participation improved some aspects of patient experience among hospitals with prior good performance. However, hospitals with historically poor performance did not benefit from ACO participation.

Practice Implications:

Prior care coordination and quality improvement experience position Medicare ACOs for greater success in terms of patient experience. Hospital leaders need to consider the potential negative consequences of ACO participation and the hospital’s preparedness for care coordination.
An Exploratory Study of Mild Cognitive Impairment of Retired Professional Contact Sport Athletes
Authors: Baker John G. , Leddy John J. , Hinds Andrea L. , Haider Mohammad N. , Shucard Jennifer , Sharma Tania , Hernandez Sergio , Durinka Joel , Zivadinov Robert , Willer Barry S.
Published: August 2018

Objective:

To test the hypothesis that mild cognitive impairment (MCI) rates are higher among retired professional contact sport athletes than in noncontact athlete controls and compare history of contact sports with other MCI risk factors.

Setting:

University Concussion Management Clinic.

Participants:

Twenty-one retired National Football League and National Hockey League players and 21 aged-matched noncontact athlete controls.

Designs:

Case-control.

Main Measures:

Comprehensive criteria were used to assess MCI based on the following: Wisconsin Card Sorting Test, Delis-Kaplan Executive Function System; Trail Making Parts A and B; Wechsler Adult Intelligence Scale–Third Edition subtests; Neuropsychological Assessment Battery Memory Module List Learning, Story Learning, and Naming subtests; and Controlled Oral Word Association Test. The Wide Range Achievement Test was used as a proxy measure for IQ. Atherosclerotic cardiovascular disease risk factors were self-reported and blood cholesterol was measured. Depression was measured by the Beck Depression Inventory-II (BDI).

Results:

Eight contact sport athletes (38%) and 3 noncontact athletes (14%) met MCI criteria (P = .083). Contact sport athletes' scores were significantly worse on Letter Fluency and List B Immediate Recall. Contact athletes were more obese, had more vascular risk factors, and had higher scores on the BDI than controls.

Conclusion:

Athletes with a history of playing professional contact sports had more vascular risk factors and higher depression scores. MCI rates were somewhat higher, though not significant.
Informing the Revolution: A Needs Assessment of Ultrasound Knowledge and Skills Among Graduating Physician Assistant Students
Authors: Barnett Melissa , Pillow M. Tyson , Carnell Jennifer , Rohra Anita , DeSandro Stephanie , Gardner Aimee K.
Published: August 2018

Purpose

We performed a needs assessment to understand how existing physician assistant (PA) program curricula and clinical training affect students' ultrasound knowledge, skills, and competence and prepare students for performing ultrasound techniques in clinical practice.

Methods

Students graduating from a PA program completed a 23-item questionnaire examining their ultrasound training experiences, their self-assessment of competency, and their demographics. Students also completed a 15-item ultrasound knowledge assessment.

Results

Thirty-eight of 39 students (97%) completed the survey. Students received little hands-on ultrasound training, with the most hands-on training being offered during emergency medicine (44.7%), obstetrics and gynecology (42.1%), and inpatient internal medicine (39.5%) rotations. This lack of preparedness was reflected in a mean score of 47.1% (±16.4%) on the ultrasound knowledge assessment. Most students (84.2%) indicated that the ultrasound instruction they received during clinical rotations was insufficient to prepare them for clinical practice, and 84.2% desired a formal ultrasound training program in the PA program curriculum.

Conclusions

Existing PA program curricula are insufficient for developing critical skills related to ultrasonography.
Normal Variant Occipital Pneumatization
Authors: Tomblinson Courtney M. , Deep Nicholas L. , Fletcher Geoffrey P. , Nelson Kent D. , Patel Ameet C. , Weindling Steven M. , Lane John I. , Hoxworth Joseph M.
Published: August 2018

Objective:

Evaluate prevalence and pattern of occipital pneumatization (OP).

Patients:

Individuals with imaging evidence of OP on computed tomography (CT).

Intervention(s):

High resolution CT scans of the temporal bone.

Main Outcome Measure:

The prevalence and pattern of OP on 1000 CT scans performed at a large academic healthcare system.

Results:

OP had a prevalence of 11.8% (n = 118) while occipital condyle pneumatization occurred in only 0.3%. Occipital air cells were right-sided in 27.1% (n = 32), left-sided in 51.7% (n = 61), and bilateral in 21.2% (n = 25), and OP was contiguous with the occipitomastoid suture. In cases of unilateral OP, the contralateral jugular foramen demonstrated relative enlargement (p = 0.006), but a direct association could not be established.

Conclusions:

The occipital bone is an accessory site of skull base pneumatization in 11.8% of the population undergoing temporal bone CT, while air cell extension into the occipital condyle occurs more rarely. These occipital air cells have a left-sided predilection and are always in direct proximity to the occipitomastoid suture, suggesting developmental egress from the mastoid. OP is a normal variant and lacks features of craniocervical pneumatization, which is a rare disorder.
Pediatric face transplantation: a viable option?
Authors: Dorante Miguel I. , Tasigiorgos Sotirios , Pomahac Bohdan
Published: August 2018

Purpose of review

Face transplantation is no longer a young field. Reported outcomes suggest that this life-enhancing transplantation is viable and ethically justified for appropriate patients. Given that pediatric hand transplantation has been performed with promising reported outcomes, it is time to consider how to properly expand the field of face transplantation into pediatric patients.

Recent findings

Appropriate collaboration between adult and pediatric colleagues can mitigate risks associated with expanding surgical innovation between respective patient demographics. The reported outcomes of the first pediatric hand transplant question the appropriateness of increasing immunosuppression burden to a patient on an existing regimen for prior solid organ allotransplantion. Young donor allografts prove to be more resilient, however, implying that managing rejection episodes is key to long-term viability. Expanding face transplants into a younger population must consider the social functions of the face, and may facilitate healthy personal development given the cultural value appearance has in real life and in social media.

We believe that pediatric face transplantation is not just a viable option, but an ethically reasonable one as long as the field proceeds with cautious optimism.
Caring for Parents After the Death of a Child
Authors: October Tessie , Dryden-Palmer Karen , Copnell Beverley , Meert Kathleen L.
Published: August 2018

Objectives:

To describe the health outcomes of bereaved parents and identify practical strategies for critical care providers as they support and provide anticipatory guidance to bereaved parents.

Data Sources:

PubMed and PsycInfo databases with search terms of bereavement, grief, with parent and pediatric or child complimented by personal experience and knowledge.

Study Selection:

We sought studies describing parental health outcomes and needs of bereaved parents after the death of their child.

Data Synthesis:

A narrative literature review was performed and framed from the perspective of PICU providers who care for bereaved parents. We aimed to describe experiences of grief and short- and long-term consequences and approaches to the care of parents and families in the immediate period and in the months after the death of a child.

Conclusions:

The death of a child is a traumatic experience that can put parents at risk for adverse mental and physical health during bereavement. Health professionals working in PICUs can benefit from knowing these risks to best support bereaved parents, both during their child’s hospitalization and in the early postdeath period. The bereavement experience of parents is an adaptive process, and ongoing professional support may be required for vulnerable families. After the child’s hospitalization and death, a bereavement follow-up meeting with PICU physician(s) and staff may allow parents to gain additional information, emotional support, and provide an opportunity for parents to give feedback on their experiences.
Comparing Youth-Friendly Health Services to the Standard of Care Through “Girl Power-Malawi”: A Quasi-Experimental Cohort Study
Authors: Rosenberg Nora E. , Bhushan Nivedita L. , Vansia Dhrutika , Phanga Twambilile , Maseko Bertha , Nthani Tiyamike , Libale Colleta , Bamuya Catherine , Kamtsendero Linda , Kachigamba Annie , Myers Laura , Tang Jennifer , Hosseinipour Mina C. , Bekker Linda-Gail , Pettifor Audrey E.
Published: August 2018

Background:

Adolescent girls and young women (AGYW) face challenges to seeking HIV and sexual and reproductive health services in sub-Saharan Africa. Integrated approaches designed for AGYW may facilitate service uptake, but rigorous evaluation is needed.

Methods:

Four comparable public-sector health centers were selected in Malawi and randomly assigned to a service delivery model. One offered “standard of care” (SOC), consisting of vertical HIV testing, family planning, and sexually transmitted infection management in adult-oriented spaces, by providers without extra training. Three offered youth-friendly health services (YFHS), consisting of the same SOC services in integrated youth-dedicated spaces and staffed by youth-friendly peers and providers. In each health center, AGYW aged 15–24 years were enrolled and followed over 12 months to determine use of HIV testing, condoms, and hormonal contraception. The SOC and YFHS models were compared using adjusted risk differences and incidence rate ratios.

Findings:

In 2016, 1000 AGYW enrolled (N = 250/health center). Median age was 19 years (interquartile range = 17–21 years). Compared with AGYW in the SOC, those in the YFHS models were 23% [confidence interval (CI): 16% to 29%)] more likely to receive HIV testing, 57% (CI: 51% to 63%) more likely to receive condoms, and 39% (CI: 34% to 45%) more likely to receive hormonal contraception. Compared with AGYW in the SOC, AGYW in the YFHS models accessed HIV testing 2.4 (CI: 1.9 to 2.9) times more, condoms 7.9 (CI: 6.0 to 10.5) times more, and hormonal contraception 6.0 (CI: 4.2 to 8.7) times more.

Conclusions:

A YFHS model led to higher health service use. Implementation science is needed to guide scale-up.
Solid Pseudo-Papillary Tumor Mimicking as Complicated Pseudocyst
Authors: Turpin Sophie , Perron Marjorie , Vairy Stéphanie , Bénali Sébastien , Damphousse Amélie
Published: August 2018

Pancreatic neoplasm is very rare in the pediatric population. Malignant tumors represent less than 0.2% of pediatric cancer-related mortality. Pancreas lesions can be from exocrine or endocrine origin or present themselves as cystic masses. Clinical, biological, and radiological findings usually are sufficient to establish diagnosis, but in some cases, they may be misleading. We present the case of a young patient presenting a pancreatic mass where anatomical and metabolic characteristics of the lesion were discordant to the final diagnosis.
Bones and muscular dystrophies: what do we know?
Authors: Wood Claire L. , Straub Volker
Published: August 2018

Purpose of review

Muscle and bone are intrinsically linked, and therefore, it is not surprising that many muscular dystrophies are associated with impaired bone health and increased risk of osteoporosis. Osteoporotic fracture is an important and preventable cause of morbidity and mortality. This article will firstly review the general causes of impaired bone health in muscular dystrophies and then focus on the evidence available for the diagnosis and treatment of osteoporosis in specific conditions.

Recent findings

With the exception of DMD, there is a paucity of data regarding bone health in muscular dystrophies. However, it appears that in common with all types of muscular dystrophies that cause a significant level of muscle weakness and disability there is an increased risk of falls, fractures and decreased vitamin D levels. A better understanding of the extent of the impaired bone health and underlying causes could help to identify potential new therapeutic agents and aid clinical care.

It would be prudent for clinicians to assess fracture risk in their muscular dystrophy patients and if appropriate, arrange surveillance and recommend vitamin D supplementation. Additionally, fracture should be considered in any patient presenting with new-onset bone pain.
Artificial intelligence for the public sector: opportunities and challenges of cross-sector collaboration
Authors: Mikhaylov Slava Jankin , Esteve Marc , Campion Averill
Published: August 2018

Public sector organizations are increasingly interested in using data science and artificial intelligence capabilities to deliver policy and generate efficiencies in high-uncertainty environments. The long-term success of data science and artificial intelligence (AI) in the public sector relies on effectively embedding it into delivery solutions for policy implementation. However, governments cannot do this integration of AI into public service delivery on their own. The UK Government Industrial Strategy is clear that delivering on the AI grand challenge requires collaboration between universities and the public and private sectors. This cross-sectoral collaborative approach is the norm in applied AI centres of excellence around the world. Despite their popularity, cross-sector collaborations entail serious management challenges that hinder their success. In this article we discuss the opportunities for and challenges of AI for the public sector. Finally, we propose a series of strategies to successfully manage these cross-sectoral collaborations.

This article is part of a discussion meeting issue ‘The growing ubiquity of algorithms in society: implications, impacts and innovations’.
Is privacy
privacy
?
Authors: Nissim Kobbi , Wood Alexandra
Published: August 2018

This position paper observes how different technical and normative conceptions of privacy have evolved in parallel and describes the practical challenges that these divergent approaches pose. Notably, past technologies relied on intuitive, heuristic understandings of privacy that have since been shown not to satisfy expectations for privacy protection. With computations ubiquitously integrated in almost every aspect of our lives, it is increasingly important to ensure that privacy technologies provide protection that is in line with relevant social norms and normative expectations. Similarly, it is also important to examine social norms and normative expectations with respect to the evolving scientific study of privacy. To this end, we argue for a rigorous analysis of the mapping from normative to technical concepts of privacy and vice versa. We review the landscape of normative and technical definitions of privacy and discuss specific examples of gaps between definitions that are relevant in the context of privacy in statistical computation. We then identify opportunities for overcoming their differences in the design of new approaches to protecting privacy in accordance with both technical and normative standards.

This article is part of a discussion meeting issue ‘The growing ubiquity of algorithms in society: implications, impacts and innovations’.
How should we regulate artificial intelligence?
Authors: Reed Chris
Published: August 2018

Using artificial intelligence (AI) technology to replace human decision-making will inevitably create new risks whose consequences are unforeseeable. This naturally leads to calls for regulation, but I argue that it is too early to attempt a general system of AI regulation. Instead, we should work incrementally within the existing legal and regulatory schemes which allocate responsibility, and therefore liability, to persons. Where AI clearly creates risks which current law and regulation cannot deal with adequately, then new regulation will be needed. But in most cases, the current system can work effectively if the producers of AI technology can provide sufficient transparency in explaining how AI decisions are made. Transparencyex postcan often be achieved through retrospective analysis of the technology's operations, and will be sufficient if the main goal is to compensate victims of incorrect decisions.Ex antetransparency is more challenging, and can limit the use of some AI technologies such as neural networks. It should only be demanded by regulation where the AI presents risks to fundamental rights, or where society needs reassuring that the technology can safely be used. Masterly inactivity in regulation is likely to achieve a better long-term solution than a rush to regulate in ignorance.

This article is part of a discussion meeting issue ‘The growing ubiquity of algorithms in society: implications, impacts and innovations'.
Algorithmic accountability
Authors: Shah Hetan
Published: August 2018

There is enormous opportunity for positive social impact from the rise of algorithms and machine learning. But this requires a licence to operate from the public, based on trustworthiness. There are a range of concerns relating to how algorithms might be held to account in areas affecting the public sphere. This paper outlines a number of approaches including greater transparency, monitoring of outcomes and improved governance. It makes a case that public sector bodies that hold datasets should be more confident in negotiating terms with the private sector. It also argues that all regulators (not just data regulators) need to wake up to the challenges posed by changing technology. Other improvements include diversity of the workforce, ethics training, codes of conduct for data scientists, and new deliberative bodies. Even if these narrower issues are solved, the paper poses some wider concerns including data monopolies, the challenge to democracy, public participation and maintaining the public interest.

This article is part of a discussion meeting issue ‘The growing ubiquity of algorithms in society: implications, impacts and innovations’.
The public accountability of social platforms: lessons from a study on bots and trolls in the Brexit campaign
Authors: Bastos Marco , Mercea Dan
Published: August 2018

In this article, we review our study of 13 493 bot-like Twitter accounts that tweeted during the UK European Union membership referendum debate and disappeared from the platform after the ballot. We discuss the methodological challenges and lessons learned from a study that emerged in a period of increasing weaponization of social media and mounting concerns about information warfare. We address the challenges and shortcomings involved in bot detection, the extent to which disinformation campaigns on social media are effective, valid metrics for user exposure, activation and engagement in the context of disinformation campaigns, unsupervised and supervised posting protocols, along with infrastructure and ethical issues associated with social sciences research based on large-scale social media data. We argue for improving researchers' access to data associated with contentious issues and suggest that social media platforms should offer public application programming interfaces to allow researchers access to content generated on their networks. We conclude with reflections on the relevance of this research agenda to public policy.

This article is part of a discussion meeting issue ‘The growing ubiquity of algorithms in society: implications, impacts and innovations'.
Pneumococcal vaccine impacts on the population genomics of non-typeable Haemophilus influenzae
Authors: Cleary David , Devine Vanessa , Morris Denise , Osman Karen , Gladstone Rebecca , Bentley Stephen , Faust Saul , Clarke Stuart
Published: August 2018

The implementation of pneumococcal conjugate vaccines (PCVs) has led to a decline in vaccine-type disease. However, there is evidence that the epidemiology of non-typeable Haemophilus influenzae (NTHi) carriage and disease can be altered as a consequence of PCV introduction. We explored the epidemiological shifts in NTHi carriage using whole genome sequencing over a 5-year period that included PCV13 replacement of PCV7 in the UK’s National Immunization Programme in 2010. Between 2008/09 and 2012/13 (October to March), nasopharyngeal swabs were taken from children <5 years of age. Significantly increased carriage post-PCV13 was observed and lineage-specific associations with Streptococcus pneumoniae were seen before but not after PCV13 introduction. NTHi were characterized into 11 discrete, temporally stable lineages, congruent with current knowledge regarding the clonality of NTHi. The increased carriage could not be linked to the expansion of a particular clone and different co-carriage dynamics were seen before PCV13 implementation when NTHi co-carried with vaccine serotype pneumococci. In summary, PCV13 introduction has been shown to have an indirect effect on NTHi epidemiology and there exists both negative and positive, distinct associations between pneumococci and NTHi. This should be considered when evaluating the impacts of pneumococcal vaccine design and policy.
Direct Crystal Formation from Micronized Bone and Lactic Acid: The Writing on the Wall for Calcium-Containing Crystal Pathogenesis in Osteoarthritis?
Authors: Bulysheva Anna A. , Sori Nardos , Francis Michael P.
Published: August 2018

Introduction

Pathological calcium-containing crystals accumulating in the joints, synovial fluid, and soft tissues are noted in most elderly patients, yet arthritic crystal formation remains idiopathic. Interestingly, elevated lactic acid and bone erosion are frequently among the comorbidities and clinical features of patients with highest incidence of crystal arthropathies. This work shows that bone particulates (modeling bone erosion) dissolve in lactic acid and directly generate crystals, possibly presenting a mechanism for crystal accumulation in osteoarthritis.

Methods and Results

Micronized human bone (average particle size of 160μm x 79μm) completely dissolved in lactic acid in 48 hours, and in synovial fluid with 500mM lactic acid in 5 days, generating birefringent rhomboid and rod-shaped crystals. SEM analysis with energy dispersive x-ray spectroscopy of these crystals showed average dimensions of around 2μm x 40μm, which contained oxygen, calcium and phosphorous at 8.64:1.85:1. Raman spectroscopy of the generated crystals further showed 910/cm and 1049/cm peaks, aligning with calcium oxalate monohydrate and calcium pyrophosphate, respectively.

Conclusions

This work shows that lactic acid and micronized mineralized bone together directly generate calcium-containing crystals. These observations may provide insights into the elusive etiology of arthritis with crystal involvement, possibly indicating lactic acid as a clinical target for treatment.
A combination of transcription factors mediates inducible interchromosomal pairing
Authors: Kim Seungsoo , Dunham Maitreya J , Shendure Jay
Published: August 2018

Remodeling of the three-dimensional organization of a genome has been previously described (e.g. condition-specific pairing or looping), but it remains unknown which factors specify and mediate such shifts in chromosome conformation. Here we describe an assay, MAP-C (Mutation Analysis in Pools by Chromosome conformation capture), that enables the simultaneous characterization of hundreds of cis or trans-acting mutations for their effects on a chromosomal contact or loop. As a proof of concept, we applied MAP-C to systematically dissect the molecular mechanism of inducible interchromosomal pairing between HAS1pr-TDA1pr alleles in Saccharomyces yeast. We identified three transcription factors, Leu3, Sdd4 (Ypr022c), and Rgt1, whose collective binding to nearby DNA sequences is necessary and sufficient for inducible pairing between binding site clusters. Rgt1 contributes to the regulation of pairing, both through changes in expression level and through its interactions with the Tup1/Ssn6 repressor complex. HAS1pr-TDA1pr is the only locus with a cluster of binding site motifs for all three factors in both S. cerevisiae and S. uvarum genomes, but the promoter for HXT3, which contains Leu3 and Rgt1 motifs, also exhibits inducible homolog pairing. Altogether, our results demonstrate that specific combinations of transcription factors can mediate condition-specific interchromosomal contacts, and reveal a molecular mechanism for interchromosomal contacts and mitotic homolog pairing.