bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibody Formation in Transfusion Therapy
Authors: Passwater Michael
Published: February 2018

The production of antibodies following blood transfusions is a complex process that involves many recipient and donor factors. Inflammation in the recipient is one important factor. As knowledge of the immune system, of oxygen, carbon dioxide, and nitric oxide pathways, and of hemostasis grows, more specific therapies will allow precise manipulation of the immune system and safer transfusions. Communication of patients' transfusion and immunotherapy histories with the laboratory, attention to detail in labeling pretransfusion specimens, checking patient and blood product identification before administration, and closely monitoring patients during transfusions remain critical to minimizing risks during transfusion therapy.
Does a Dedicated Lumen for Parenteral Nutrition Administration Reduce the Risk of Catheter-Related Bloodstream Infections? A Systematic Literature Review
Authors: Gavin Nicole Clare , Button Elise , Castillo Maria Isabel , Ray-Barruel Gillian , Keogh Samantha , McMillan David J. , Rickard Claire M.
Published: February 2018

Guidelines recommend using single-lumen central vascular access devices (CVADs) for the administration of parenteral nutrition (PN) or lipid-based solutions, or a dedicated lumen on a multilumen CVAD. Publications reviewed by the authors reported comparative rates of catheter-related bloodstream infection (CR-BSI) in patients with CVADs who received PN through a dedicated lumen compared with those who had PN administered through multilumen CVADs. Two studies included 650 patients with 1349 CVADs. CR-BSIs were equally distributed between the 2 groups. Both studies were poorly reported and had significant risk of bias. These results should be interpreted with caution.
Maternal Bereavement
Authors: Abdel Razeq Nadin M. , Al-Gamal Ekhlas
Published: February 2018

The death of a newborn infant is one of the most devastating situations a mother could experience. The aim of this study was to understand bereavement and its associated meanings as lived and experienced by the mothers who lost their newborn infants in the intensive care units of hospitals in Jordan. Data were generated using semistructured face-to-face interviews with 12 mothers who had the experience. A qualitative phenomenological approach was used for data analysis. Three main themes emerged from the analysis: (1) longing and grieving, as natural emotional responses to the loss; (2) adaptive work of coping, as the mothers internalized meanings to cope with their loss; and (3) moving forward but with a scar, as the mothers moved on with their lives while they carried the unforgettable memories of the newborns’ death experience. Bereavement support services should be considered vitally important as soon as the news of a newborn’s death is delivered to the mother. Palliative care nurses and other health care providers should give careful attention to the meanings that the mothers attached to the loss and support each bereaved mother’s spiritual values and effective coping mechanisms.
Community-Based Palliative Care Leader Perspectives on Staffing, Recruitment, and Training
Authors: Dudley Nancy , Chapman Susan , Spetz Joanne
Published: February 2018

To assess perspectives of US community-based palliative care program leaders on staffing, recruitment, and training, a qualitative descriptive study was conducted. Leaders (n = 20) from academic medical centers, large integrated and community health systems, home health and hospice organizations, and the Veterans Administration were recruited. Three major categories emerged that influence community-based palliative care workforce team composition across settings: (1) staffing models and recruitment are influenced by setting and workforce experience, (2) training varies by setting, and (3) demand exceeds supply of trained workforce. Participants described a hybrid approach used in academic and community settings to complete an interdisciplinary team by leveraging social work and chaplaincy from inpatient departments and home health and hospice. Physician-led interdisciplinary teams in academic settings and teams more often led by nurse practitioners in community settings were reported. Community program leaders expressed the desire to recruit nurses with home health and hospice experience because of the ability to work independently. Training was described as more often on-the-job in community settings. Turnover related to the lack of a properly trained workforce was described as one of the biggest barriers to palliative care development.
Rural Readmissions in the Palliative Care Vacuum
Authors: Durie Craig , Tanksley-Bowe Catherine
Published: February 2018

Palliative care consultation is associated with reduced health care costs and improved quality of life while reducing length of stay. Small rural hospitals lack the depth of multidisciplinary resources to provide inpatient palliative care consult services. The purpose of this research was to assess the need for palliative care service in rural hospitals, while examining for a difference in hospital readmission rates in hospitals lacking palliative consult services. Data were obtained from the Pennsylvania Health Cost Containment Counsel including 3 hospitals with palliative programs and 3 without. Inclusion criteria were admissions for a patient carrying a diagnosis appropriate for palliative consultation between the last quarter of 2014 and 2015. There were 1394 index patients admitted to 3 rural hospitals lacking a palliative consult program. There was a higher rate of readmissions at the nonpalliative hospitals, 71.6% versus 55.1% (P < .001). Data suggest there is a need for palliative telemedicine services to meet needs in rural hospitals.
Autoimmune Encephalitis With Multiple Autoantibodies
Authors: Kim Albert E. , Kang Peter , Bucelli Robert C. , Ferguson Cole J. , Schmidt Robert E. , Varadhachary Arun S. , Day Gregory S.
Published: February 2018

Introduction:

Indications for autoantibody testing in patients with rapid-onset cognitive impairment have expanded in step with the growing number of disease-associated autoantibodies and clinical syndromes. Although increased access to autoantibody testing has broadened our understanding of the spectrum of autoimmune encephalitis (AE), it has also produced new challenges associated with deciphering the contributions of disease-associated autoantibodies in patients with atypical clinical features and/or multiple autoantibodies. These challenges are illustrated through presentation of a patient with AE associated with autoantibodies against intracellular and cell-surface neuronal antigens. The implications of detection of multiple autoantibodies are considered in the context of relevant literature, and used to frame a diagnostic and therapeutic approach.

Case Report:

A previously well 67-year-old man presented with encephalopathy and psychosis, impaired visual fixation, and ataxia, emerging over 3 months. Hu, CRMP-5, and NMDAR autoantibodies were identified in the cerebrospinal fluid. No malignancy was discovered despite extensive investigations. An aggressive course of immunotherapy temporarily stabilized his course; however, the patient succumbed to his illness 10 months after symptom onset. Lack of sustained response to immunotherapy and neuropathologic findings suggested that AE associated with Hu antibodies was primarily responsible for this patient’s progressive decline.

Conclusions:

Multiple autoantibodies may be detected in patients with AE. When antibodies targeting intracellular and cell-surface antigens are detected together, investigation and treatment of syndromes associated with intracellular antibodies should be prioritized, acknowledging the link between these antibodies and irreversible neuronal injury. In paraneoplastic cases, prognosis may be tied to early detection and treatment of the underlying malignancy.
RANK and RANK Ligand Expression in Parotid Gland Carcinomas
Authors: Franchi Alessandro , Taverna Cecilia , Simoni Antonella , Pepi Monica , Mannelli Giuditta , Fasolati Martina , Gallo Oreste
Published: February 2018

Recently, it has been reported that deregulation of the receptor activator of NFkB ligand (RANKL)/RANK signaling axis results in salivary gland tumor development in a mouse transgenic model. The aim of this study was to ascertain RANKL and RANK protein expression in a series of primary parotid gland carcinomas and to correlate it with clinicopathologic parameters. Formalin-fixed paraffin-embedded tumor samples from 46 consecutive cases of parotid gland carcinoma were selected for this study. For comparison, we examined a group of 40 randomly chosen parotid gland adenomas, including 20 pleomorphic adenomas, 10 myoepitheliomas, and 10 Warthin tumors. Immunohistochemical analysis for RANK and RANKL was conducted on tissue microarrays. Overall, 33 carcinomas (71.7%) were scored as positive for RANK and 25 (54.3%) for RANKL. The expression of both RANK and RANKL was significantly higher in carcinomas than in adenomas as only 6 (15%) adenomas were positive for RANK, and RANKL was negative in all benign tumors (P<0.001 for both, Fisher exact test). Some histologic types, including salivary duct carcinoma, mucoepidermoid carcinoma, and carcinoma ex-pleomorphic adenoma presented a high frequency of RANK and RANKL expression. No significant correlation was observed between RANK/RANKL expression and clinical parameters. Our study indicates that the expression of RANK and RANKL in parotid gland neoplasms is associated with the acquisition of a malignant phenotype and this pathway may represent an attractive therapeutic target in patients with parotid gland carcinomas.
Reexpansion Pulmonary Edema in Pediatrics
Authors: Hirsch Alexander W. , Nagler Joshua
Published: February 2018

Reexpansion pulmonary edema is a rare complication that may occur after drainage of pneumothorax or pleural effusion. A number of factors have been identified that increase the risk of developing reexpansion pulmonary edema, and pathophysiologic mechanisms have been postulated. Patients may present with radiographic findings alone or may have signs or symptoms that prompt evaluation and diagnosis. Clinical presentations range from mild cough to respiratory failure and hemodynamic compromise. Treatment strategies are supportive, and should be tailored to match the severity of the condition.
The Evolution of Trauma in Los Angeles County Over More Than a Decade
Authors: Chen Sean Shaohua , Bosson Nichole , Gausche-Hill Marianne , Gorospe Deidre D. , Tadeo Richard E.
Published: February 2018

Objective:

Explore trends in trauma incidence and mortality rates in Los Angeles County.

Design:

Data for patients treated at Los Angeles County trauma centers from 2000 to 2011 were analyzed for this study. Age-adjusted incidence and mortality rates were calculated by gender, race, injury type, injury severity, and mechanism of injury. Trends were assessed using linear regression to determine the annual percentage change (APC).

Results:

There were 223 773 patients included. The trauma incidence rate increased by 14.6% driven by an increase in blunt injury of 5.4% annually (P < .05). Penetrating injury decreased at −6.9% APC (P < .01). Mortality rate decreased at −11.5% APC (P < .01), with reduction in both blunt (−6.8% APC [P < .01]) and penetrating injuries (−16.7% APC [P < .01]). The trends in mortality persisted with stratification by age, gender, race, and injury severity score.

Conclusion:

In this mature trauma system, the trauma incidence increased slightly from 2000 to 2011, while the mortality steadily declined. Public health officials in other areas could perform a similar self-evaluation to describe and monitor injury events and trends in their jurisdictions, a reassessment of priority and trauma system resource allocation, which will directly benefit the regional population.
Orbital Interstitial Fluid: Evidence of a Potential Pathway for Extracranial Cerebrospinal Fluid Absorption
Authors: Sachs Jeffrey R. , Zapadka Michael E. , Elster Allen D.
Published: February 2018

Background and Purpose

The aim of the study was to describe the prevalence and characteristics of orbital interstitial fluid seen on magnetic resonance (MR) images of infants and young children.

Materials and Methods

Fat-suppressed axial T2-weighted MR images of 100 consecutive infants and young children (<6 years) without orbital pathology were retrospectively reviewed by 2 neuroradiologists. The presence, location, and extent of high-signal orbital interstitial fluid were characterized and tabulated as a function of age.

Results

Orbital interstitial fluid was detected in 90 (90%) of the 100 subjects overall, present in 100% (75/75) of infants and children younger than 3 years, 75% (12/16) of those aged 3 to 5 years, and 33% (3/9) of those aged 5 to 6 years. The fluid was bilateral and symmetric in all cases. Two morphologic patterns were distinguished, which often co-existed: (1) a focal discrete curvilinear band of fluid in the posterior-lateral orbit, more common in younger patients, and (2) an ill-defined, lace-like pattern primarily in the superior orbit seen in subjects of all ages.

Conclusions

Orbital interstitial fluid as detected by fat-suppressed T2-weighted MR imaging is a nearly universal finding in infants and young children and should not be considered pathologic. It may have either a focal or lace-like pattern or both. Orbital interstitial fluid decreases in size and prevalence as a function of age but is still present in nearly half of children aged 4 to 6 years. Possible explanations concerning the nature and origin of this fluid are presented, including the fascinating possibility that the fluid represents an extracranial pathway for outflow of cerebrospinal fluid.
Phenotypic Multiorgan Involvement of Subclinical Disease as Quantified by Magnetic Resonance Imaging in Subjects With Prediabetes, Diabetes, and Normal Glucose Tolerance
Authors: Storz Corinna , Rospleszcz Susanne , Lorbeer Roberto , Hetterich Holger , Auweter Sigrid D. , Sommer Wieland , Machann Jürgen , Gatidis Sergios , Rathmann Wolfgang , Heier Margit , Linkohr Birgit , Meisinger Christa , Reiser Maximilian , Hoffmann Udo , Peters Annette , Schlett Christopher L. , Bamberg Fabian
Published: February 2018

Introduction

Detailed mechanisms in the pathophysiology of diabetes disease are poorly understood, but structural alterations in various organ systems incur an elevated risk for cardiovascular events and adverse outcome. The aim of this study was to compare multiorgan subclinical disease phenotypes by magnetic resonance (MR) imaging to study differences between subjects with prediabetes, diabetes, and normal controls.

Materials and Methods

Subjects without prior cardiovascular disease were enrolled in a prospective case-control study and underwent multiorgan MR for the assessment of metabolic and arteriosclerotic alterations, including age-related white matter changes, hepatic proton density fat fraction, visceral adipose tissue volume, left ventricular remodeling index, carotid plaque, and late gadolinium enhancement. Magnetic resonance features were summarized in a phenotypic-based score (range, 0–6). Univariate, multivariate correlation, and unsupervised clustering were performed.

Results

Among 243 subjects with complete multiorgan MR data sets included in the analysis (55.6 ± 8.9 years, 62% males), 48 were classified as subjects with prediabetes and 38 as subjects with diabetes. The MR phenotypic score was significantly higher in subjects with prediabetes and diabetes as compared with controls (mean score, 3.00 ± 1.04 and 2.69 ± 0.98 vs 1.22 ± 0.98, P < 0.001 respectively), also after adjustment for potential confounders. We identified 2 clusters of MR phenotype patterns associated with glycemic status (P < 0.001), independent of the MR score (cluster II–metabolic specific: odds ratio, 2.49; 95% CI, 1.00–6.17; P = 0.049).

Discussion

Subjects with prediabetes and diabetes have a significantly higher phenotypic-based score with a distinctive multiorgan phenotypic pattern, which may enable improved disease characterization.
Continuous Hepatic Arterial Multiphase Magnetic Resonance Imaging During Free-Breathing
Authors: Weiss Jakob , Notohamiprodjo Mike , Taron Jana , Martirosian Petros , Nickel Dominik , Bamberg Fabian , Nikolaou Konstantin , Othman Ahmed E.
Published: February 2018

Purpose

The aim of this study was to evaluate the feasibility of a prototype volume-interpolated breath-hold examination (VIBE) sequence using compressed sensing (VIBECS) for rapid multiphase arterial magnetic resonance imaging (MRI) at different temporal resolution during free-breathing in comparison with a conventional breath-hold approach (VIBESTD).

Material and Methods

A total of 40 patients with liver malignancies were prospectively included in this study and underwent contrast-enhanced liver MRI at 1.5 T to evaluate the performance of VIBECS for rapid arterial multiphase imaging. An additional 40 patients examined with a VIBESTD were included serving as standard of reference. The VIBECS study cohort was subdivided into 2 groups (each n = 20). In both groups, VIBECS was continuously acquired for 60 seconds starting with the contrast agent administration (group A, temporal resolution 4 seconds; group B, temporal resolution 8 seconds). Subsequently, the time point with the subjectively best image quality was selected and defined as hepatic arterial dominant (HAD) phase. Overall image quality, lesion conspicuity, vessel contrast, and artifacts of HAD phase were assessed by 2 radiologists independently on a 5-point Likert scale (5 = excellent) and compared with arterial phase images of VIBESTD. In addition, signal attenuation/time curves of VIBECS were plotted for each patient to quantify the hepatic arterial enhancement.

Results

No patients were excluded and all HAD phases were reliably recorded in the investigated VIBECS cohort. Most commonly, HAD was observed at the ninth time point (36 seconds after intravenous contrast injection) in group A and at the fifth time point (40 seconds after intravenous contrast injection) in group B. Timing with VIBESTD was only adequate in 65% (26/40). Image quality, lesion conspicuity, and vessel contrast were good to excellent without significant differences between both VIBECS groups (P ≥ 0.2) and with significantly higher reading scores as compared with VIBESTD with respect to lesion conspicuity (P ≤ 0.006) and image quality (group B; P < 0.001). VIBECS showed reconstruction artifacts, which were significantly higher in group A (P = 0.001). Mean peak arterial enhancement was observed at the ninth time point (36 seconds) in group A and at the sixth (48 seconds) in group B.

Conclusion

VIBECS allows for robust multiphase arterial imaging during free-breathing at high spatial and temporal resolution (preferably 8 seconds) with improved image quality and lesion conspicuity as compared with VIBESTD.
Simple Technique for Reducing the Buccal Fat Pad During Mandibular Orthognathic Surgery
Authors: Kawase-Koga Yoko , Shibata Kaoru , Kimoto Akira , Watanabe Masato , Chikazu Daichi
Published: February 2018

Sagittal split ramus osteotomy and intraoral vertical ramus osteotomy are commonly performed for the correction of jaw deformities. However, during mandibular orthognathic surgeries such as sagittal split ramus osteotomy and intraoral vertical ramus osteotomy , the authors sometimes encounter exposure of the buccal fat pad (BFP), which decreases the surgical field. The exposed BFP makes it difficult to perform these operations, may result in unexpected complications, and may increase the operation time. Therefore, the authors herein describe a simple, safe, and convenient technique for reducing the volume of the exposed BFP during mandibular orthognathic surgery using an electric knife in the coagulation mode.
A Reduction Technique for Depressed Medial Maxillary Fractures
Authors: Cho Hyun M. , Kim Hyung M. , Hwang Kun
Published: February 2018

The authors developed a technique for reducing the fractured segment by introducing an elevator through the accessory maxillary ostium (AMO).

Through an upper gingivolabial vestibular incision, the fractured segments were exposed. In cases where no cleft was available for inserting the elevator, the blunt end of a Cottle elevator was inserted into the AMO via a nasal approach. The curved blunt end of a Cottle elevator was inserted into the middle meatus and the AMO was felt at the medial wall of the maxillary sinus. With gentle pressure, the tip was pushed into the maxillary sinus, and then pushed forward about 2 cm. An upward force was applied until the depressed segment was reduced to its original position. Through a gingivolabial vestibular incision, alignment of the reduced segments could be seen. Miniplate fixation can be applied. If the reduced segments are stable or too many segments are present, the fracture can be stabilized using tissue glue.

The authors propose that in medial maxillary fractures where no cleft for the elevator is available, the fractured segment can be mobilized by introducing an elevator through the AMO.
Postextraction Dental Implant in the Aesthetic Zone, Socket Shield Technique Versus Conventional Protocol
Authors: Bramanti Ennio , Norcia Antonio , Cicciù Marco , Matacena Giada , Cervino Gabriele , Troiano Giuseppe , Zhurakivska Khrystyna , Laino Luigi
Published: February 2018

The aim of this randomized controlled trial was to evaluate the survival rate, the marginal bone level, and the aesthetic outcome; at 3 years’ follow-up, of dental implants placed into a high-esthetic aesthetic zone by comparing 2 techniques of postextraction implant with immediate loading: the socket shied technique and the conventional insertion technique.

Several clinical studies suggested that the avulsion of a dental element causes dimensional alterations of both soft and hard tissues at the postextractive site. To increase the aesthetic outcomes, the “socket-shield technique” has been proposed. This method involves maintaining the vestibular root portion and immediate insertion of the dental implant in close proximity to the root.

Patients enrolled in this study were randomized to receive a postextraction implant in the aesthetic zone, either with the socket shied technique or with the conventional insertion technique. Implant survival, marginal bone level, and the pink aesthetic score were the outcomes evaluated.

Implant survival rate was 100% in both the groups at 3 years. Implants inserted with the socket shield technique showed better values of both marginal bone level and pink aesthetic score (P < 0.05).

Although such preliminary results need to be further confirmed, the socket shield technique seems to be a safe surgical technique that allows an implant rehabilitation characterized by better aesthetic outcomes.
Despair of Treatment
Authors: Shabanloei Reza , Ebrahimi Hossein , Ahmadi Fazlollah , Mohammadi Eesa , Dolatkhah Roya
Published: February 2018

Cirrhotic patients are exposed to illness progression and life-threatening side effects. The nature of the disease, its incurability, limitations of liver transplantation, and the intensity of threatening conditions lead to psychological distress for the patients and change in their perception of the treatment. To provide holistic care, it is necessary to clarify the patient's perception of the treatment. The aim of this study was to clarify cirrhotic patients' perception of their treatment. This qualitative study was carried out through a content analysis approach. The participants were 15 cirrhotic patients. Data were collected via semistructured, in-depth interviews and analyzed on the basis of the Granheme and Landman method. Despair of treatment was revealed through four categories: (1) disease perception (quiet start and quiet death, living in an aggravating limitation, intensifying threatening conditions), (2) self-perception (living in the shadow of death, loss of self, preferring family to oneself), (3) perception of treatment (difficulty of treatment compliance, believed to be incurable, treatment conditioned to die, treatment limitation), and (4) spirituality-religion (destiny and divine test, asking God instead of doctors). The study shows that despair of treatment is considered as one of the main concerns of cirrhotic patients. Nurses should program their surveillance to support patients effectively based on the study findings.
Disposal of Endoscopic Accessories After Use
Authors: Agrawal Deepak , Shoup Valerie , Montgomery Amy , Wosik Jedrek , Rockey Don C.
Published: February 2018

Significant amounts of medical waste are generated in endoscopy units. Improper disposal has significant health, cost, and environmental implications. The aim of this study was to better understand the appropriateness of handling of medical waste in the endoscopy unit. This is a validated survey completed online and in person by endoscopy staff and gastroenterologists. Main outcome measurements include the method of disposal of endoscopic accessories (snares, dilating balloons, endoscopic retrograde cholangiopancreatography wires, and sphincterotomes) and nasogastric tubes and whether or not in the appropriate disposal bin (i.e., in sharps container, red bags, or regular trash). The appropriateness of the method of disposal was determined per Occupational Safety and Health Administration guidelines. Respondents included 783 endoscopy staff members and 352 gastroenterologists. Fifty-eight percent of endoscopy staff members and 65% of gastroenterologists handled simple endoscopic accessories as regulated medical waste instead of regular trash. Furthermore, 27% of respondents discarded endoscopic accessories as sharps, although they are not considered sharps. Nearly one third of respondents discarded nasogastric tubes and other endoscopic accessories differently, even though both would have same degree of contamination. Only 7 respondents (0.6%) understood disposal costs. All but 23 respondents (2%) felt that medical personnel should be better informed about medical waste. Most medical waste from endoscopy laboratories is handled inappropriately. Endoscopy staff and gastroenterologists' understanding of recommended disposal methods for endoscopic accessories is poor. The data have major financial and environmental implications.
The Beneficial Effects of Minimizing Blood Loss in Pancreatoduodenectomy
Authors: Seykora Thomas F. , Ecker Brett L. , McMillan Matthew T. , Maggino Laura , Beane Joal D. , Fong Zhi Ven , Hollis Robert H. , Jamieson Nigel B. , Javed Ammar A. , Kowalsky Stacy J. , Kunstman John W. , Malleo Giuseppe , Poruk Katherine E. , Soares Kevin , Valero Vicente , Velu Lavanniya K. P. , Watkins Ammara A. , Vollmer Charles M.
Published: February 2018

Objective:

The aim of this study was to elucidate the impact of intraoperative blood loss on outcomes following pancreatoduodenectomy (PD).

Background:

The negative impact of intraoperative blood loss on outcomes in PD has long been suspected but not well characterized, particularly those factors that may be within surgeons’ control.

Methods:

From 2001 to 2015, 5323 PDs were performed by 62 surgeons from 17 institutions. Estimated blood loss (EBL) was discretized (0 to 300, 301 to 750, 751 to 1300, and >1300 mL) using optimal scaling methodology. Multivariable regression, adjusted for patient, surgeon, and institutional variables, was used to identify associations between EBL and perioperative outcomes. Factors associated with both increased and decreased EBL were elucidated. The relative impact of surgeon-modifiable contributors was estimated through beta coefficient standardization.

Results:

The median EBL of the series was 400 mL [interquartile range (IQR) 250 to 600]. Intra-, post-, and perioperative transfusion rates were 15.8%, 24.8%, and 37.2%, respectively. Progressive EBL zones correlated with intra- but not postoperative transfusion in a dose-dependent fashion (P < 0.001), with a key threshold of 750 mL EBL (8.14% vs 40.9%; P < 0.001). Increasing blood loss significantly correlated with poor perioperative outcomes. Factors associated with increased EBL were trans-anastomotic stent placement, neoadjuvant chemotherapy, pancreaticogastrostomy reconstruction, multiorgan or vascular resection, and elevated operative time, of which 38.7% of the relative impact was “potentially modifiable” by the surgeon. Conversely, female sex, small duct, soft gland, minimally invasive approach, pylorus-preservation, biological sealant use, and institutional volume (≥67/year) were associated with decreased EBL, of which 13.6% was potentially under the surgeon's influence.

Conclusion:

Minimizing blood loss contributes to fewer intraoperative transfusions and better perioperative outcomes for PD. Improvements might be achieved by targeting modifiable factors that influence EBL.
Increased Rate of Long-term Mortality Among Burn Survivors
Authors: Mason Stephanie A. , Nathens Avery B. , Byrne James P. , Diong Christina , Fowler Robert A. , Karanicolas Paul J. , Moineddin Rahim , Jeschke Marc G.
Published: February 2018

Objective:

To estimate long-term mortality following major burn injury compared with matched controls.

Summary Background Data:

The effect of sustaining a major burn injury on long-term life expectancy is poorly understood.

Methods:

Using health administrative data, all adults who survived to discharge after major burn injury between 2003 and 2013 were matched to between 1 and 5 uninjured controls on age, sex, and the extent of both physical and psychological comorbidity. To account for socioeconomic factors such as residential instability and material deprivation, we also matched on marginalization index. The primary outcome was 5-year all-cause mortality, and all patients were followed until death or March 31, 2014. Cumulative mortality estimates were estimated using the Kaplan–Meier method. Cox proportional hazards modeling was used to estimate the association of burn injury with mortality.

Results:

In total, 1965 burn survivors of mean age 44 (standard deviation 17) years with median total body surface area burn of 15% [interquartile range (IQR) 5–15] were matched to 8671 controls and followed for a median 5 (IQR 2.5–8) years. Five-year mortality was significantly greater among burn survivors (11 vs 4%, P < 0.001). The hazard ratio was greatest during the first year (4.15, 95% CI 3.17–5.42), and declined each year thereafter, reaching 1.65 (95% CI 1.02–2.67) in the fifth year after discharge. Burn survivors had increased mortality related to trauma (mortality rate ratio, MRR 9.8, 95% CI 5–19) and mental illness (MRR 9.1, 95% CI 4–23).

Conclusions:

Burn survivors have a significantly higher rate of long-term mortality than matched controls, particularly related to trauma and mental illness. Burn follow-up should be focused on injury prevention, mental healthcare, and detection and treatment of new disease.
Understanding the evolution of personality requires the study of mechanisms behind the development and life history of personality traits
Authors: Trillmich Fritz , Müller Thorben , Müller Caroline
Published: February 2018

Research on animal personality explains the coexistence of distinct behavioural phenotypes within a species and demonstrates limits to individual plasticity. However, the mechanisms guiding the lifelong development of personality should receive more attention, because many elements of personality are emergent properties of interactions between the environment and an individual's genetic background. In these interactions, mechanisms (e.g. genetic regulatory networks, epigenetic processes and neuroendocrine regulation) influencing personality may be modified. An approach integrating proximate mechanisms with a view of lifelong personality development will crucially improve understanding stability, plasticity and inter-individual variability of personalities and clarify the effects of selection on the phenomenon.
Local extinction of the Asian tiger mosquito (
Aedes albopictus
) following rat eradication on Palmyra Atoll
Authors: Lafferty Kevin D. , McLaughlin John P. , Gruner Daniel S. , Bogar Taylor A. , Bui An , Childress Jasmine N. , Espinoza Magaly , Forbes Elizabeth S. , Johnston Cora A. , Klope Maggie , Miller-ter Kuile Ana , Lee Michelle , Plummer Katherine A. , Weber David A. , Young Ronald T. , Young Hillary S.
Published: February 2018

The Asian tiger mosquito,
Aedes albopictus,
appears to have been extirpated from Palmyra Atoll following rat eradication. Anecdotal biting reports, collection records, and regular captures in black-light traps showed the species was present before rat eradication. Since then, there have been no biting reports and no captures over 2 years of extensive trapping (black-light and scent traps). By contrast, the southern house mosquito,
Culex quinquefasciatus,
was abundant before and after rat eradication. We hypothesize that mammals were a substantial and preferred blood meal for
Aedes
, whereas
Culex
feeds mostly on seabirds. Therefore, after rat eradication, humans and seabirds alone could not support positive population growth or maintenance of
Aedes
. This seems to be the first documented accidental secondary extinction of a mosquito. Furthermore, it suggests that preferred host abundance can limit mosquito populations, opening new directions for controlling important disease vectors that depend on introduced species like rats.
Bone resorption: supporting immunometabolism
Authors: van Niekerk Gustav , Mitchell Megan , Engelbrecht Anna-Mart
Published: February 2018

Activation of the immune system is associated with an increase in the breakdown of various peripheral tissues, including bone. Despite the widely appreciated role of inflammatory mediators in promoting bone resorption, the functional value behind this process is not completely understood. Recent advances in the field of immunometabolism have highlighted the metabolic reprogramming that takes place in activated immune cells. It is now believed that the breakdown of peripheral tissue provides metabolic substrates to fuel metabolic anabolism in activated immune cells. We argue that phosphate, liberated by bone resorption, plays an indispensable role in sustaining immune cell metabolism. The liberated phosphate is then incorporated into macromolecules such as nucleotides and phospholipids, and is also used for the phosphorylation of metabolites (e.g. glycolytic intermediates). In addition, magnesium, also liberated during the breakdown of bone, is an essential cofactor required by various metabolic enzymes which are upregulated in activated immune cells. Finally, calcium activates various additional molecules involved in immune cell migration. Taken together, these factors suggest a key role for bone resorption during infection.
Spatially extended hybrid methods: a review
Authors: Smith Cameron A. , Yates Christian A.
Published: February 2018

Many biological and physical systems exhibit behaviour at multiple spatial, temporal or population scales. Multiscale processes provide challenges when they are to be simulated using numerical techniques. While coarser methods such as partial differential equations are typically fast to simulate, they lack the individual-level detail that may be required in regions of low concentration or small spatial scale. However, to simulate at such an individual level throughout a domain and in regions where concentrations are high can be computationally expensive. Spatially coupled hybrid methods provide a bridge, allowing for multiple representations of the same species in one spatial domain by partitioning space into distinct modelling subdomains. Over the past 20 years, such hybrid methods have risen to prominence, leading to what is now a very active research area across multiple disciplines including chemistry, physics and mathematics. There are three main motivations for undertaking this review. Firstly, we have collated a large number of spatially extended hybrid methods and presented them in a single coherent document, while comparing and contrasting them, so that anyone who requires a multiscale hybrid method will be able to find the most appropriate one for their need. Secondly, we have provided canonical examples with algorithms and accompanying code, serving to demonstrate how these types of methods work in practice. Finally, we have presented papers that employ these methods on real biological and physical problems, demonstrating their utility. We also consider some open research questions in the area of hybrid method development and the future directions for the field.
Primordial sex facilitates the emergence of evolution
Authors: Sinai Sam , Olejarz Jason , Neagu Iulia A. , Nowak Martin A.
Published: February 2018

Compartments are ubiquitous throughout biology, and they have very likely played a crucial role at the origin of life. Here we assume that a protocell, which is a compartment enclosing functional components, requires
N
such components in order to be evolvable. We calculate the timescale in which a minimal evolvable protocell is produced. We show that when protocells fuse and share information, the timescales polynomially in
N
. By contrast, in the absence of fusion, the worst-case scenario is exponential in
N
. We discuss the implications of this result for the origin of life and other biological processes.
ELKS active zone proteins as multitasking scaffolds for secretion
Authors: Held Richard G. , Kaeser Pascal S.
Published: February 2018

Synaptic vesicle exocytosis relies on the tethering of release ready vesicles close to voltage-gated Ca
2+
channels and specific lipids at the future site of fusion. This enables rapid and efficient neurotransmitter secretion during presynaptic depolarization by an action potential. Extensive research has revealed that this tethering is mediated by an active zone, a protein dense structure that is attached to the presynaptic plasma membrane and opposed to postsynaptic receptors. Although roles of individual active zone proteins in exocytosis are in part understood, the molecular mechanisms that hold the protein scaffold at the active zone together and link it to the presynaptic plasma membrane have remained unknown. This is largely due to redundancy within and across scaffolding protein families at the active zone. Recent studies, however, have uncovered that ELKS proteins, also called ERC, Rab6IP2 or CAST, act as active zone scaffolds redundant with RIMs. This redundancy has led to diverse synaptic phenotypes in studies of ELKS knockout mice, perhaps because different synapses rely to a variable extent on scaffolding redundancy. In this review, we first evaluate the need for presynaptic scaffolding, and we then discuss how the diverse synaptic and non-synaptic functional roles of ELKS support the hypothesis that ELKS provides molecular scaffolding for organizing vesicle traffic at the presynaptic active zone and in other cellular compartments.
Energy approach to brittle fracture in strain-gradient modelling
Authors: Placidi Luca , Barchiesi Emilio
Published: February 2018

In this paper, we exploit some results in the theory of irreversible phenomena to address the study of quasi-static brittle fracture propagation in a two-dimensional isotropic continuum. The elastic strain energy density of the body has been assumed to be geometrically nonlinear and to depend on the strain gradient. Such generalized continua often arise in the description of microstructured media. These materials possess an intrinsic length scale, which determines the size of internal boundary layers. In particular, the non-locality conferred by this internal length scale avoids the concentration of deformations, which is usually observed when dealing with local models and which leads to mesh dependency. A scalar Lagrangian damage field, ranging from zero to one, is introduced to describe the internal state of structural degradation of the material. Standard Lamé and second-gradient elastic coefficients are all assumed to decrease as damage increases and to be locally zero if the value attained by damage is one. This last situation is associated with crack formation and/or propagation. Numerical solutions of the model are provided in the case of an obliquely notched rectangular specimen subjected to monotonous tensile and shear loading tests, and brittle fracture propagation is discussed.
The combined impacts of experimental defaunation and logging on seedling traits and diversity
Authors: Granados Alys , Bernard Henry , Brodie Jedediah F.
Published: February 2018

Animals can have both positive (e.g. via seed dispersal) and negative (e.g. via herbivory) impacts on plants. The net effects of these interactions remain difficult to predict and may be affected by overhunting and habitat disturbance, two widespread threats to tropical forests. Recent studies have documented their separate effects on plant recruitment but our understanding of how defaunation and logging interact to influence tropical tree communities is limited. From 2013 to 2016, we followed the fate of marked tree seedlings (
n
= 1489) from 81 genera in and outside experimental plots. Our plots differentially excluded small, medium and large-bodied mammal herbivores in logged and unlogged forest in Malaysian Borneo. We assessed the effects of experimental defaunation and logging on taxonomic diversity and plant trait (wood density, specific leaf area, fruit size) composition of seedling communities. Although seedling mortality was highest in the presence of all mammal herbivores (44%), defaunation alone did not alter taxonomic diversity nor plant trait composition. However, herbivores (across all body sizes) significantly reduced mean fruit size across the seedling community over time (95% confidence interval (CI): −0.09 to −0.01), particularly in logged forest (95% CI: −0.12 to −0.003). Our findings suggest that impacts of mammal herbivores on plant communities may be greater in forests with a history of disturbance and could subsequently affect plant functional traits and ecological processes associated with forest regeneration.
How well do force fields capture the strength of salt bridges in proteins?
Authors: Ahmed Mustapha Carab , Papaleo Elena , Lindorff-Larsen Kresten
Published: February 2018

Salt bridges form between pairs of ionisable residues in close proximity and are important interactions in proteins. While salt bridges are known to be important both for protein stability, recognition and regulation, we still do not have fully accurate predictive models to assess the energetic contributions of salt bridges. Molecular dynamics simulations is one technique that may be used study the complex relationship between structure, solvation and energetics of salt bridges, but the accuracy of such simulations depend on the force field used. We have used NMR data on the B1 domain of protein G (GB1) to benchmark molecular dynamics simulations. Using enhanced sampling simulations, we calculated the free energy of forming a salt bridge for three possible ionic interactions in GB1. The NMR experiments showed that these interactions are either not formed, or only very weakly formed, in solution. In contrast, we show that the stability of the salt bridges is slightly overestimated in simulations of GB1 using six commonly used combinations of force fields and water models. We therefore conclude that further work is needed to refine our ability to model quantitatively the stability of salt bridges through simulations, and that comparisons between experiments and simulations will play a crucial role in furthering our understanding of this important interaction.
Big data analysis of mitochondrial DNA substitution models: A regression approach elucidating the effects of codon position and neighboring nucleotides
Authors: Levinstein Hallak Keren , Tzur Shay , Rosset Saharon
Published: February 2018

We build on the up-to-date version of Phylotree, a comprehensive and continuously updating phylogeny of global human mtDNA variations (van Oven and Kayser 2009), to better understand the substitution mechanism of the mitochondrial DNA (mtDNA) and its most influential factors. We do so by composing Poisson and negative-binomial regression models relating the rate of occurrence of mtDNA substitutions to various factors. Important factors we identify include the identity of the codon at each position, confirming previous findings about the biological significance of different codons for the same amino acid. Importantly, we also identify a significant effect of neighboring sites. This effect cannot be attributed solely to CpG pairs. A similar effect of neighboring sites was recently described for autosomal DNA substitutions, and we speculate it is related to the basic mutational mechanism itself. Once codon composition and context are taken into account, there is no significant difference in substitution rate between different genes in mtDNA.
The cryo-EM structure of the SF3b spliceosome complex bound to a splicing modulator reveals a pre-mRNA substrate competitive mechanism of action
Authors: Finci Lorenzo I. , Zhang Xiaofeng , Huang Xiuliang , Zhou Qiang , Tsai Jennifer , Teng Teng , Agrawal Anant , Chan Betty , Irwin Sean , Karr Craig , Cook Andrew , Zhu Ping , Reynolds Dominic , Smith Peter G. , Fekkes Peter , Buonamici Silvia , Larsen Nicholas A.
Published: February 2018

Somatic mutations in spliceosome proteins lead to dysregulated RNA splicing and are observed in a variety of cancers. These genetic aberrations may offer a potential intervention point for targeted therapeutics. SF3B1, part of the U2 small nuclear RNP (snRNP), is targeted by splicing modulators, including E7107, the first to enter clinical trials, and, more recently, H3B-8800. Modulating splicing represents a first-in-class opportunity in drug discovery, and elucidating the structural basis for the mode of action opens up new possibilities for structure-based drug design. Here, we present the cryogenic electron microscopy (cryo-EM) structure of the SF3b subcomplex (SF3B1, SF3B3, PHF5A, and SF3B5) bound to E7107 at 3.95 Å. This structure shows that E7107 binds in the branch point adenosine-binding pocket, forming close contacts with key residues that confer resistance upon mutation: SF3B1R1074H and PHF5AY36C. The structure suggests a model in which splicing modulators interfere with branch point adenosine recognition and supports a substrate competitive mechanism of action (MOA). Using several related chemical probes, we validate the pose of the compound and support their substrate competitive MOA by comparing their activity against both strong and weak pre-mRNA substrates. Finally, we present functional data and structure–activity relationship (SAR) on the PHF5AR38C mutation that sensitizes cells to some chemical probes but not others. Developing small molecule splicing modulators represents a promising therapeutic approach for a variety of diseases, and this work provides a significant step in enabling structure-based drug design for these elaborate natural products. Importantly, this work also demonstrates that the utilization of cryo-EM in drug discovery is coming of age.
1-(2-Amino-4,5-dimethylphenyl)ethanone
Authors: Bosch Eric , Jeffries Laura
Published: February 2018

The molecule of the title compound, C10H13NO, also referred to as 2-amino-4,5-dimethylacetophenone, lies on a crystallographic mirror plane with four molecules in the orthorhombic unit cell and features an intramolecular N—H...O hydrogen bond. In the crystal, the molecules are linked by N—H...O hydrogen bonds, forming ribbons along theaaxis that pack to form sheets lying in the (010) plane.