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Anophthalmia/microphthalmia (A/M) is a genetically heterogeneous birth defect for which the etiology is unknown in more than 50% of patients. We used exome sequencing with the ACE Exome(TM) (Personalis, Inc; 18 cases) and UCSF Genomics Core (21 cases) to sequence 28 patients with A/M and four patients with varied developmental eye defects. In the 28 patients with A/M, we identified de novo mutations in three patients (OTX2, p.(Gln91His), RARB, p.Arg387Cys and GDF6, p.Ala249Glu) and inherited mutations in STRA6 in two patients. In patients with developmental eye defects, a female with cataracts and cardiomyopathy had a de novo COL4A1 mutation, p.(Gly773Arg), expanding the phenotype associated with COL4A1 to include cardiomyopathy. A male with a chorioretinal defect, microcephaly, seizures and sensorineural deafness had two PNPT1 mutations, p.(Ala507Ser) and c.401-1G>A, and we describe eye defects associated with this gene for the first time. Exome sequencing was efficient for identifying mutations in pathogenic genes for which there is no clinical testing available and for identifying cases that expand phenotypic spectra, such as the PNPT1 and COL4A1-associated disorders described here.

It is well established that mammalian skeletal muscles exhibit a considerable degree of plasticity and one of the main determining factors of this plasticity is the activity pattern and duration of motoneurone discharge. Lesions to the right substantia nigra pars compacta (SNpc) of six adult rats were made to determine whether altered output from the SNpc ultimately leads to a change in the expression of proteins in contralateral skeletal muscles. After 4 months, altered motor performance was identified by the administration of amphetamine. After 7 months, 30–70% of dopaminergic cells in the SNpc had been destroyed. The protein content of muscles was then quantified from densitometric scans of gels, and expressed as a % of the amount of actin (the protein used as a reference in this study). The lesion affected the expression of different protein isoforms in the fast- and slow-twitch muscles. In slow-twitch soleus muscles, the lesion decreased the proportion of α-tropomyosin and increased the proportion of β-tropomyosin. In the fast-twitch extensor digitorum longus muscles, the lesion increased the proportion of the fast isoform of troponin-T1f, and decreased the proportions of the two isoforms of myosin light chain. This study establishes a connection between the chronic effects of a lesion to the SNpc, with a loss of dopaminergic neurones, impaired motor performance, and altered expression of proteins in skeletal muscle. The implication of these results is that the altered motor function observed in Parkinson’s disease may be associated with alterations to the expression of skeletal muscle proteins. [ABSTRACT FROM AUTHOR]

Ethical principles regarding respect for patient autonomy in medical decision-making and the impact of religion, culture, and other issues on clinical care have been extensively reviewed in the medical literature. At the same time, despite physicians having an understanding of the underlying ethical principles in clinical decision-making, challenges arise when managing complicated clinical problems for which medical treatment is available, but not acceptable to the patient. For example, many anesthesiologists are challenged when caring for one of Jehohah's Witnesses who refuses to receive blood or blood products despite the potential consequences of doing so., Competing Interests: Disclosure Neither author has any conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Targeted muscle reinnervation (TMR) is an effective technique for the prevention and management of phantom limb pain (PLP) and residual limb pain (RLP) among amputees. The purpose of this study was to evaluate symptomatic neuroma recurrence and neuropathic pain outcomes between cohorts undergoing TMR at the time of amputation (ie, acute) versus TMR following symptomatic neuroma formation (ie, delayed)., Methods: A cross-sectional, retrospective chart review was conducted using patients undergoing TMR between 2015 and 2020. Symptomatic neuroma recurrence and surgical complications were collected. A subanalysis was conducted for patients who completed Patient-Reported Outcome Measurement Information System (PROMIS) pain intensity, interference, and behavior scales and an 11-point numeric rating scale (NRS) form., Results: A total of 105 limbs from 103 patients were identified, with 73 acute TMR limbs and 32 delayed TMR limbs. Nineteen percent of the delayed TMR group had symptomatic neuromas recur in the distribution of original TMR compared with 1% of the acute TMR group ( P < 0.05). Pain surveys were completed at final follow-up by 85% of patients in the acute TMR group and 69% of patients in the delayed TMR group. Of this subanalysis, acute TMR patients reported significantly lower PLP PROMIS pain interference ( P < 0.05), RLP PROMIS pain intensity ( P < 0.05), and RLP PROMIS pain interference ( P < 0.05) scores in comparison to the delayed group., Conclusions: Patients who underwent acute TMR reported improved pain scores and a decreased rate of neuroma formation compared with TMR performed in a delayed fashion. These results highlight the promising role of TMR in the prevention of neuropathic pain and neuroma formation at the time of amputation., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Physician assistants (PAs) are an essential part of the healthcare team who improve access and efficiencies in patient care. A better understanding of the impact and current utilization of PAs in plastic and reconstructive surgery is needed. The purpose of this national survey was to evaluate the role and scope of practice of PAs in academic plastic surgery, as well as characterize current trends of PA utilization, compensation, and perceived value from a PA perspective., Methods: A voluntary, anonymous 50-question survey was distributed via SurveyMonkey to practicing PAs at 98 academic plastic surgery programs. The survey included questions about employment characteristics, involvement in clinical research and academic work, structural organization, academic benefits, compensation, and position held., Results: Ninety-one PAs from 35 plastic surgery programs completed the survey and were included (overall program response rate = 36.8%, participants response rate = 30.4%). Practice environments included outpatient clinics, the operating room, and inpatient care. Most commonly, respondents supported multiple surgeons as opposed to one surgeon's practice. For 57% of respondents, compensation is based on a tiered system that accounts for specialty and experience. The reported mode base salary range corroborates national averages and most reported annual bonuses based on merit. The majority of respondents felt valued in their role., Conclusions: Through this national survey, we provide granularity as to how PAs are utilized and compensated in academic plastic surgery. We offer insight into the overall perceived value from a PA perspective that helps define the role and will ultimately help strengthen collaboration., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Purpose: Neuropathic pain can be life altering and difficult to treat. Nerves can be compressed along their path in the upper extremities, resulting in chronic neuropathic pain. This study was performed to evaluate the effectiveness and safety of multiple concomitant distal nerve decompressions for the treatment of upper extremity nerve pain., Methods: A retrospective review of patients from a single surgeon's academic practice was performed to identify those undergoing nerve decompressions for an indication of "pain" as the referring diagnosis between April 2020 and June 2021. The primary outcomes included patient-reported severity of pain using the Visual Analog Scale and quality-of-life measures, including level of frustration, depression, and impact on quality of life attributable to pain on a similar 0-10 Likert scale. Complications, if any, were also determined., Results: Eleven patients were identified to have undergone multiple concurrent nerve decompressions for the indication of upper extremity pain. All sites chosen for decompression were found to be provocative, ie, elicited increased pain on examination with compression. The median number of decompressions performed was 5 (interquartile range, 4-6), ranging from 3 to 7. The mean follow-up time was 5 months (SD, 3.43 months). The average pain over the last month and the average pain over the past week had significant improvement at the final follow-up, and there was a statistically significant decrease in the patient-reported mean impact of pain on quality of life following decompressions (preoperative, 5.8; postoperative, 3.6; P  = .017; 95% confidence interval, 0.2-4.3). No complications were identified., Conclusions: Performing multiple concomitant nerve decompressions of the upper extremities is safe and effective in the treatment of chronic neuropathic pain following upper extremity trauma., Type of Study/level of Evidence: Therapeutic IV., (© 2022 The Authors.)

Peripheral nerve injuries often result in life-altering functional deficits even with optimal management. Unlike the central nervous system, peripheral nerves have the ability to regenerate lost axons after injury; however, axonal regeneration does not equate to full restoration of function. To overcome this physiological shortcoming, advances in nerve regeneration and repair are paramount, including electrical stimulation, gene therapy, and surgical technique advancements.

Despite the widely acknowledged role of the anthropogenic drivers of climate change, there has been little success in developing a clear overview of the strengths and weaknesses of counter-measures or developing a consensus on their application. Problems with conventional approaches arise from the strongly coupled, multidisciplinary issues involved and the long timescales (centuries or more) over which some key processes operate. Here we outline an alternative approach based on experience gained in risk assessment for an area with similar challenges-the geological disposal of radioactive waste. Utilization of such risk assessment approaches and tools to facilitate a holistic, top-down synthesis of the interactions between the key features, events and processes driving climate change and constraining responses to it, are illustrated. We especially focus on visual presentations that encourage dialog between both specialists and non-technical stakeholders. These can thus form a basis to assist balancing responses in terms of energy policy, modified socio-economic boundary conditions and environmental management., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Phantom limb pain (PLP) and residual limb pain (RLP) are debilitating sequelae of major limb amputation. Targeted muscle reinnervation (TMR), when performed at the time of amputation, has been shown to be effective for management of this pain; however, its long-term effects and the longitudinal trend of patient-reported outcomes is unknown. The purpose of this study was to characterize the longitudinal patient-reported outcomes of pain and quality of life following TMR at the time of initial amputation., Study Design: A prospective case series of patients undergoing major limb amputation with TMR performed at the time of amputation were followed from October 2015 to December 2020 with outcomes measured 3, 6, 12, and 18 months or longer after amputation and TMR. Outcomes included patient-reported severity of PLP and RLP as measured by the numeric rating scale (NRS). Secondary outcomes included the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference and Pain Behavior Questionnaires., Results: Eighty-one patients with 83 treated limbs were included in the study, and 23 patients completed surveys at 18 months or later, with an average follow-up time of 2.4 years. By 3 months after operation, all patient-reported outcomes for PLP and RLP were consistent with previously reported data that demonstrated superiority to non-TMR amputees. Mixed-model linear regression analysis showed that PLP NRS severity scores continued to improve over the study period (p = 0.022). The remaining outcomes for RLP severity and PROMIS quality-of-life measures demonstrated that these scores remained stable over the study period (p > 0.05)., Conclusion: TMR is an effective surgical procedure that improves the chances of having reduced RLP and PLP when performed at the time of amputation, and our study demonstrates the long-term durability of its efficacy., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hip disarticulations are proximal lower extremity amputations with high postoperative complication and mortality rates. The purpose of the study was to evaluate hip disarticulation outcomes at our institution. Targeted Muscle Reinnervation (TMR) is an effective surgical technique shown to reduce pain in amputees. A secondary goal of the study was to evaluate the impact of implementing TMR on this patient population., Methods: A retrospective review was performed for patients who underwent hip disarticulation with and without TMR between 2009 and 2020. Information on one-year mortality, thirty-day complication rates, operation times, surgical charges, and pain scores was collected., Results: Fifty-one patients underwent hip disarticulation, eight of which had TMR performed at the time of their hip disarticulation. The one-year mortality rate was 37% with 30-day infection, readmission, reoperation, and rates of 37%, 39%, and 27% respectively. The thirty-day major complication rate was 47% overall but not statistically significantly different between groups. There were no differences between groups with regard to 30-day readmission, reoperation, and infection rates., Conclusions: Our results represent one of the largest series of hip disarticulation outcomes. Performing TMR at the time of hip disarticulation did not negatively affect outcomes and may be a beneficial adjunct to improve pain. Further research is warranted., Competing Interests: The authors have no financial disclosures or conflicts of interest., (© 2022 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

Background: Hypoxia due to closure at the ostiomeatal complex is widely considered one of the major pathogenic mechanisms leading to chronic inflammation in chronic rhinosinusitis (CRS). The objective of this study was to develop and characterize an oxygen-generating biomaterial (OGB) as an innovative treatment strategy for CRS., Methods: An OGB was fabricated by coating hydrophobic beeswax (BW, 15mg or 30mg) on the surface of calcium peroxide - catalase complex (CPO-CA, 30mg) and characterized using scanning electron microscopy (SEM). In vitro releases of both oxygen and hydrogen peroxide (H 2 O 2 ) were spectrophotometrically quantified, and cytotoxicity in human sinonasal epithelial cells (HSNECs) was evaluated. The influence of OGB on transepithelial Cl - secretion was also determined by pharmacologically manipulating HSNECs, cultured under hypoxic conditions, in Ussing chambers., Results: Three groups of OGBs: (1) CPO only; (2) CPO coated with CA and BW (1:1 ratio, CPO-CA(1)-BW(1)); and (3) CPO coated with CA and BW (1:0.5 ratio, CPO-CA(1)-BW(0.5) were analyzed for accumulated oxygen release over 7 days: highest release (mmol/mg) was observed in CPO-CA(1)-BW(1) = 0.11 ± 0.003, followed by CPO-CA(1)-BW(0.5) = 0.08 ± 0.010, and CPO = 0.05 ± 0.004 (p < 0.0001). H 2 O 2 production (mM) was significantly higher in CPO (1.87 ± 0.50) compared to CPO-CA (1)-BW(1) (0.00 ± 0.00) (p < 0.001) after 24 h. CPO-CA(1)-BW(1) showed significantly reduced cytotoxicity and increased Cl - transport compared to the CPO group., Conclusion: A novel OGB (CPO-CA-BW complex) exhibited sustained oxygen release over 7 days without significant cytotoxicity after 24 h in vitro. Preclinical studies evaluating the efficacy of OGB in CRS are warranted, especially for potential therapy in an obstruction-based CRS model., (© 2021 ARS-AAOA, LLC.)

Peripheral nerve injuries in children can result in devastating lifelong deficits. Because of the time-sensitive nature of muscle viability and the limited speed of nerve regeneration, early recognition and treatment of nerve injuries are essential to restore function. Innovative surgical techniques have been developed to combat the regenerative length and speed; these include nerve transfers. Nerve transfers involve transferring a healthy, expendable donor nerve to an injured nerve to restore movement and sensation. Nerve transfers are frequently used to treat children affected by conditions, including UE trauma, brachial plexus birth injury, and acute flaccid myelitis. Pediatricians play an important role in the outcomes of children with these conditions through early diagnosis and timely referrals. With this review, we aim to provide awareness of state-of-the-art surgical treatment options that significantly improve the function of children with traumatic nerve injuries, brachial plexus birth injury, and acute flaccid myelitis., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Acute flaccid myelitis (AFM) is characterized by flaccid paralysis following prodromal symptoms. Complete recovery is rare, and patients typically have residual extremity weakness. This study aimed to describe the technique and outcomes of lower extremity nerve transfers for children with AFM., Methods: A retrospective review of eight children who developed AFM in 2016 and had lower extremity nerve transfers was performed. Principles of nerve transfer were applied to develop novel nerve transfer procedures to restore function for this patient population. Pre- and postoperative muscle strength grades were reviewed, and qualitative improvements in function were recorded., Results: A variety of nerve transfers were utilized in eight patients with average time to surgery from AFM diagnosis of 15.7 months. Restoration of gluteal, femoral, hamstring, and gastrocnemius function was attempted. Variable MRC grade improvement was achieved (range MRC grade 0-4). All patients reported subjective improvements in function. Four of five patients with follow-up who underwent nerve transfers for restoration of gluteal function transitioned from wheelchair use to walking with assistive devices as their primary modes of ambulation. No donor site complications occurred., Conclusions: The unique needs of this patient population and variable patterns of residual weakness require meticulous assessment and development of individualized surgical plans. With appropriate goals and expectations in mind, functional improvement may be achieved, including return to ambulation., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Introduction: Advances in the care of soft-tissue tumors, including imaging capabilities and adjuvant radiation therapy, have broadened the indications and opportunities to pursue surgical limb salvage. However, peripheral nerve involvement and femoral nerve resection can still result in devastating functional outcomes. Nerve transfers offer a versatile solution to restore nerve function following tumor resection., Methods: Two cases were identified by retrospective review. Patient and disease characteristics were gathered. Preoperative and postoperative motor function were assessed using the Medical Research Council Muscle Scale. Patient-reported pain levels were assessed using the numeric rating scale., Results: Nerve transfers from the obturator and sciatic nerve were employed to restore knee extension. Follow up for Case 1 was 24 months, 8 months for Case 2. In both patients, knee extension and stabilization of gait without bracing was restored. Patient also demonstrated 0/10 pain (an average improvement of 5 points) with decreased neuromodulator and pain medication use., Conclusion: Nerve transfers can restore function and provide pain control benefits and ideally are performed at the time of tumor extirpation. This collaboration between oncologic and nerve surgeons will ultimately result in improved functional recovery and patient outcomes., (© 2021 Wiley Periodicals LLC.)

Changing environmental conditions are forcing natural resource managers and communities to adapt their strategies to account for global shifts in precipitation, temperature, sea level and more, all of which are occurring in addition to local human impacts. Adapting to threats from climate change requires a fundamental shift in the practice of natural resource management through the development of forward-looking "climate-smart" goals and strategies. Here we present a proof-of-concept application of a decision-support tool to help design climate-smart management actions for the watershed and coral reef management plan for Guánica Bay watershed in southwest Puerto Rico. We also explore the connection between adaptation planning and coral reef resilience, using a recently developed Puerto Rico-wide reef resilience assessment. In the first phase of the study, we used the publicly available Adaptation Design Tool to draft initial climate-smart versions of twelve proposed management actions. In the second phase, two actions (dirt road management on steep slopes, and coral reef restoration) were further refined through consultations with local experts to make more detailed design adjustments; this included the option to use information from the coral reef resilience assessment to inform design improvements. The first phase resulted in moderately detailed assessments that broadly accounted for anticipated direct and indirect effects of climate change on the planned management actions. The second phase resulted in more site-specific technical assessments and additional important design details. The expert panel charged with discussing climate-smart reef restoration around Guánica used the reef resilience assessment to guide discussion of reef restoration, highlighting the importance of having such information available for adaptation planning. This study demonstrates how climate change impacts can be effectively incorporated into a management plan at the most granular level of planning and how a structured, formalized process can be as valuable as the resulting adaptation information., Competing Interests: The affiliation of author PB with Tetra Tech, Inc. does not alter our adherence to PLOS ONE policies on sharing data and materials.

Process analytical technology (PAT) is a fast-growing field within bioprocessing that enables innovation in biological drug manufacturing. This study demonstrates novel PAT methods for monitoring multiple quality attributes simultaneously during the ultrafiltration and diafiltration (UF/DF) process operation, the final step of monoclonal antibody (mAb) purification. Size exclusion chromatography (SEC) methods were developed to measure excipients arginine, histidine, and high molecular weight (HMW) species using a liquid chromatography (LC) system with autosampler for both on-line and at-line PAT modes. The methods were applied in UF/DF studies for the comparison of single-use tangential flow filtration (TFF) cassettes to standard reusable cassettes to achieve very high concentration mAb drug substance (DS) in the order of 100-200 g/L. These case studies demonstrated that single-use TFF cassettes are a functionally equivalent, low-cost alternative to standard reusable cassettes, and that the on-line PAT measurement of purity and excipient concentration was comparable to orthogonal offline methods. These PAT applications using an on-line LC system equipped with onboard sample dilution can become a platform system for monitoring of multiple attributes over a wide dynamic range, a potentially valuable tool for biological drug development and manufacturing., (© 2021 Wiley Periodicals LLC.)

Objective: Spontaneous cerebrospinal fluid (CSF) leaks represent a unique subset of skull base pathology and require distinctive management. Perioperative evaluation and management of intracranial hypertension are essential in preventing further erosion of the skull base and development of recurrent leak. The objective of this study is to evaluate the safety and utility of an expedited protocol for recording and managing intracranial hypertension following endoscopic repair of spontaneous CSF leaks., Methods: Prospectively collected data was reviewed in patients undergoing endoscopic repair of spontaneous CSF leaks between January 2017 and March 2020. A standard intracranial pressure monitoring protocol was compared to an expedited protocol (EP), and data regarding the two groups was compared for leak location, short-term success of skull base repair, complications, hospital length of stay, and cost-based analysis., Results: Fifty-five patients (standard protocol, n = 28 vs. EP, n = 27) were included in the study. Leak location was similar between cohorts, with the lateral recess being the most common locations in both groups (37.9% vs. 40.6%; P = .90). Postoperative complications (3.6% vs. 7.4%; P = .53) and ventriculoperitoneal shunt rate (32.1% vs. 22.2%; P = .41) were similar among cohorts. There was no difference in lumbar drain complications (0% vs. 7.4%; P = .14) or recurrent leak (7.1% vs. 0%; P = .16). Length of stay was shorter in the EP group [median(interquartile range): 3(1) vs. 2 (1); P < .01]. Total hospital charges were similar between groups (median (USD/$1,000): 83.57 ± 49.58 vs. 83.93 ± 46.11; P = .18)., Conclusion: An expedited monitoring protocol shortened hospital stay without increased risk of complications., Level of Evidence: III Laryngoscope, 131:E408-E412, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: This study aimed to determine whether the length of the excised obstructed vas deferens at vasovasostomy (VV) performed for fertility is associated with semen parameters and/or pregnancy outcomes postoperatively., Material and Methods: The patients who underwent a VV at our institution from September 2004 to December 2018 were contacted via questionnaire and a chart review was performed. Linear and logistic regression models were used to determine the associations between the length of the obstructed vas deferens removed and postoperative outcomes including sperm concentration, motility, and successful pregnancy after reversal., Results: A total of 83/170 questionnaires were returned. After exclusions, a total of 35 patients were included for analysis. The mean age of the patients at the time of surgery was 40.1 years and the mean time since vasectomy 9.3 years. The mean length of the obstructed vas deferens removed during VV was 2.25 cm. The longer the vas deferens segments removed, the more significant was the increase in sperm motility at 3 and 9 months postoperatively (p=0.011 and 0.008, respectively), but decreased sperm motility at 6 months (p=0.029). In 75.9% of the patients, sperm was present postoperatively, 23.2% achieved pregnancy through natural conception, and 55.8% achieved pregnancy using assisted reproductive techniques. There was no significant relationship between the length of the vas deferens removed and sperm concentration or pregnancy achieved after surgery., Conclusion: In this cohort, the length of the excised obstructed vas deferens at VV was associated with improved sperm motility at 3 and 9 months postoperatively but not with pregnancy outcomes.

Purpose: Targeted muscle reinnervation (TMR) is a technique for the management of peripheral nerves in amputation. Phantom limb pain (PLP) and residual limb pain (RLP) trouble many patients after amputation, and TMR has been shown to reduce this pain when performed after the initial amputation. We hypothesize that TMR at the time of amputation may improve pain for patients after major upper-extremity amputation., Methods: We conducted a retrospective review of patients who underwent major upper-extremity amputation with TMR performed at the time of the index amputation (early TMR). Phantom limb pain and RLP intensity and associated symptoms were assessed using the numeric rating scale (NRS), the Patient-Reported Outcome Measurement Information System (PROMIS) Pain Intensity Short-Form 3a, the Pain Behavior Short-Form 7a, and the Pain Interference Short-Form 8a. The TMR cohort was compared with benchmarked data from a sample of upper-extremity amputees., Results: Sixteen patients underwent early TMR and were compared with 55 benchmark patients. More than half of early TMR patients were without PLP (62%) compared with 24% of controls. Furthermore, half of all patients were free of RLP compared with 36% of controls. The median PROMIS PLP intensity score for the general sample was 47 versus 38 in the early TMR sample. Patients who underwent early TMR reported reduced pain behaviors and interference specific to PLP (50 vs 53 and 41 vs 50, respectively). The PROMIS RLP intensity score was lower in patients with early TMR (36 vs 47)., Conclusions: This study demonstrates that early TMR is a promising strategy for treating pain and improving the quality of life in the upper-extremity amputee. Early TMR may preclude the need for additional surgery and represents an important technique for peripheral nerve surgery., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2021 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

The impacts of the current COVID-19 pandemic illustrate the global-level sensitivity to such threats. As understanding of major hazards is generally based on past experience and there is a lack of good historical precedents, approaches and models currently employed to assess risks and guide responses generally lack transparency and are often associated with huge, unspecified uncertainties. Fundamental challenges arise from the strongly coupled nature of the impacts of a pandemic (i.e. not only on health, but also on the entire socio-economic infrastructure) and their long-term evolution with recovery likely to take many years or, potentially, decades. Here, we outline experience gained in risk assessment within the nuclear industry, which has experience facing similar challenges (assessing long-term impacts in a strongly coupled technical system subject to socio-economic constraints), and assess options for knowledge transfer that may help manage future pandemics and other high-impact threats., (© The Author(s), under exclusive licence to Springer Japan KK, part of Springer Nature 2021.)

The life altering nature of major limb amputations may be further complicated by neuroma formation in up to 60% of the estimated 2 million major limb amputees in the United States. This can be a source of pain and functional limitation of the residual limb. Pain associated with neuromas may limit prosthetic limb use, require reoperation, lead to opioid dependence, and dramatically reduce quality of life. A number of management options have been described including excision alone, excision with repair, excision with transposition, and targeted muscle reinnervation. Targeted muscle reinnervation has been shown to reduce phantom limb and neuroma pain for patients with upper and lower extremity amputations. It may be performed at the time of initial amputation to prevent pain development or secondarily for the treatment of established pain. Encouraging outcomes have been reported, and targeted muscle reinnervation is emerging as a leading surgical technique for pain prevention in patients undergoing major limb amputations and pain management in patients with pre-existing amputations., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Background: Orthopaedic trauma etiologies are a common cause for amputation. Targeted muscle reinnervation (TMR) is a technique aimed at reducing or preventing pain and improving function. The purpose of this study was to examine postoperative phantom limb pain and residual limb pain following TMR in orthopaedic trauma amputees. In addition, postoperative rates of opioid and neuromodulator medication use were evaluated., Methods: Twenty-five patients (60% male) prospectively enrolled in a single-institution study and underwent TMR at the time of major limb amputation (48% nonmilitary trauma, 32% infection secondary to previous nonmilitary trauma, and 20% other, also secondary to trauma). Phantom limb pain and residual limb pain scores, pain temporality, prosthetic use, and unemployment status were assessed at the time of follow-up. The use of opioid and neuromodulator medications both preoperatively and postoperatively was also examined., Results: At a mean follow-up of 14.1 months, phantom limb pain and residual limb pain scores were low, with 92% of the patients reporting no pain or brief intermittent pain only. Pain scores were higher overall for male patients compared with female patients (p < 0.05) except for 1 subscore, and higher in patients who underwent amputation for infection (odds ratio, 9.75; p = 0.01). Sixteen percent of the patients reported opioid medication use at the time of the latest documented follow-up. Fifty percent of the patients who were taking opioids preoperatively discontinued use postoperatively, while 100% of the patients who were not taking opioids preoperatively discontinued postoperative use. None of the patients who were taking neuromodulator medication preoperatively discontinued use postoperatively (0 of 5). The median time to neuromodulator medication discontinuation was 14.6 months, with female patients taking longer than male patients (23 compared with 7 months; p = 0.02). At the time of the latest follow-up, the rate of reported prosthetic use was 85% for lower-extremity and 40% for upper-extremity amputees, with a rate of unemployment due to disability of 36%., Conclusions: The use of TMR in orthopaedic trauma amputees was associated with low overall pain scores at 2-year follow-up, decreased overall opioid and neuromodulator medication use, and an overall high rate of daily prosthetic use., Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The authors indicated that no external funding was received for any aspect of this work. On the Disclosure of Potential Conflicts of Interest forms, which are provided with the online version of the article, one or more of the authors checked “yes” to indicate that the author had a relevant financial relationship in the biomedical arena outside the submitted work (http://links.lww.com/JBJSOA/A154)., (Copyright © 2020 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Background: There is an ongoing effort to identify a biomarker which predicts metastatic progression of renal cell carcinoma (RCC)., Objective: To evaluate the utility of the cell cycle progression (CCP) score biomarker in predicting metastasis in RCC after local resection of pathologic T1 disease., Design, Setting, and Participants: Pathologic T1 tumors at the University of Iowa were reviewed in patients who had a radical or partial nephrectomy between 1995 and 2010. Patients with known or suspected metastasis, who had received chemotherapy, or who developed metastasis within 60 days of surgery were excluded. Final analysis included 163 patients with RCC who developed metastasis or a new primary within 5 years after surgery or had been followed for 5 years without developing metastasis., Intervention(s): Expression levels of 31 cell cycle genes and 15 control genes from the tumor were measured and reported as a CCP score., Outcome Measurements and Statistical Analysis: The sensitivity, specificity, positive predictive value, and negative predictive value for the development of a metastasis or new primary within 5 years of resection was calculated for varying CCP score cutoffs., Results and Limitations: A total of 4 (2.5%) patients developed metastasis and 7 (4.3%) developed a new primary renal tumor. A CCP score of >-0.25 had a 100% sensitivity and 43% specificity for predicting metastatic progression. A CCP score of >-0.7 had a 100% sensitivity and 20% specificity for predicting the development of a new renal primary., Conclusions: The CCP score has potential prognostic value in predicting metastatic progression and might be a useful tool for the management of patients with RCC., Patient Summary: In this study we looked at the utility of a particular gene expression profile from kidney tumors. We found that this gene expression test has the potential to identify tumors at risk of metastasis and thus could be a useful tool in the management of patients with kidney tumors., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Wound infection involving hardware can be notoriously difficult to treat, often requiring the removal of the infected implant. The goal of this study was to determine the utility of instillation negative pressure wound therapy to help eradicate infection and allow for definitive wound closure in patients without removing the infected hardware. A retrospective review was performed on the outcomes of 28 patients who presented with open wounds with exposed or infected hardware and who were treated with a combination of surgical debridement and negative pressure wound therapy with instillation (NPWTi). Eleven patients were treated for infected spinal hardware, 12 for extremity, and 5 for sternal hardware. Twenty-five of 28 (89%) patients had successful retention or replacement of hardware, with clearance of infection and healed wounds. Original hardware was maintained in 17 of 28 (61%) patients. In 11 patients, original hardware was removed, with subsequent replacement in eight of those patients after a clean wound was achieved. Average time to definitive closure was 12.6 days. Average follow-up was 135 days. This series supports NPWTi as an effective adjunct therapy to help expeditiously eradicate hardware infection, allowing for hardware retention., (© 2019 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: Pseudomonas aeruginosa is common in chronic rhinosinusitus (CRS) and frequently resistant to antibiotic treatment. We recently described the ciprofloxacin and ivacaftor-releasing biodegradable sinus stent (CISS)-a drug-delivery system that administers ciprofloxacin and the mucociliary activator (ivacaftor) at high local concentrations with prolonged mucosal contact time and sustained delivery. The objective of this study is to evaluate the efficacy of the CISS in a rabbit model of P aeruginosa (PAO1 strain) sinusitis., Methods: Ciprofloxacin/ivacaftor (double layer) was coated on biodegradable poly-D/L-lactic acid (PLLA). A total of 10 sinus stents (5 bare PLLA stent controls, 5 CISSs) were placed unilaterally in rabbit maxillary sinuses via dorsal sinusotomy after inducing infection for 1 week with PAO1. Animals were assessed 3 weeks after stent insertion with sinus culture, nasal endoscopy, computed tomography scan, histopathology, and in-vivo sinus potential difference (SPD) assay., Results: Rabbits treated with CISS had significant reductions in computed tomography (∆ Kerschner scale: control, 0.55 ± 0.92; CISS, -5.92 ± 1.69; p = 0.024) and endoscopy (control, 4.0 ± 0.0; CISS, 1.875 ± 0.74; p = 0.003) scores. A 2-log reduction of PAO1 was observed (control, -2.14 ± 0.77; CISS, 1.84 ± 1.52; p = 0.047). SPD revealed significantly increased Cl - transport in the CISS group compared with the control group (Cl - -free + forskolin ΔPD: control, -4.23 ± 1.04 mV; CISS, -18.36 ± 6.31 mV; p = 0.026). Finally, marked improvements were noted in the histology of the mucosa and submucosa in treated animals., Conclusion: The CISS had robust clinical efficacy in treating P aeruginosa rabbit sinusitis. The innovative design of double-layered drug coating on the surface of the biodegradable stent may provide therapeutic advantages over current treatment strategies for P aeruginosa sinusitis., (© 2019 ARS-AAOA, LLC.)

Globally increasing sea surface temperatures threaten coral reefs, both directly and through interactions with local stressors. More resilient reefs have a higher likelihood of returning to a coral-dominated state following a disturbance, such as a mass bleaching event. To advance practical approaches to reef resilience assessments and aid resilience-based management of coral reefs, we conducted a resilience assessment for Puerto Rico's coral reefs, modified from methods used in other U.S. jurisdictions. We calculated relative resilience scores for 103 sites from an existing commonwealth-wide survey using eight resilience indicators-such as coral diversity, macroalgae percent cover, and herbivorous fish biomass-and assessed which indicators most drove resilience. We found that sites of very different relative resilience were generally highly spatially intermixed, underscoring the importance and necessity of decision making and management at fine scales. In combination with information on levels of two localized stressors (fishing pressure and pollution exposure), we used the resilience indicators to assess which of seven potential management actions could be used at each site to maintain or improve resilience. Fishery management was the management action that applied to the most sites. Furthermore, we combined sites' resilience scores with projected ocean warming to assign sites to vulnerability categories. Island-wide or community-level managers can use the actions and vulnerability information as a starting point for resilience-based management of their reefs. This assessment differs from many previous ones because we tested how much information could be yielded by a "desktop" assessment using freely-available, existing data rather than from a customized, resilience-focused field survey. The available data still permitted analyses comparable to previous assessments, demonstrating that desktop resilience assessments can substitute for assessments with field components under some circumstances., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate preoperative scoring systems and operative management and their relation to complications in patients older than 75 years undergoing cystectomy at two academic institutions., Methods: In total, 212 patients aged 75-95 years with muscle invasive bladder cancer underwent cystectomy at the University of Utah and Central Hospital of Bolzano, Italy. The rates of Grade 3 Clavien-Dindo complications and above in radical cystectomy patients (n = 199) were compared using Eastern Cooperative Oncology Group Scores and American Society of Anesthesiologists Physical Status Classification. The rates of Grade 3 Clavien-Dindo complications and above were also compared by urinary diversion type. Logistic regression was used to control for source institution., Results: In total, 199 cases were included in the primary analysis. Neither of the preoperative scoring systems were predictive for identification of radical cystectomy patients with ⩾Grade 3 Clavien-Dindo complications. In secondary analysis (n = 212, including partial cystectomy), none of the urinary diversion types associated with radical cystectomy had a significantly different rate of complications. However, partial cystectomy (n = 13) had a significantly lower rate of complications., Conclusion: Complication rates among elderly patients undergoing cystectomy for muscle invasive bladder cancer were very high. For patients who are approved for surgery after the history and physical exam, none of our objective metrics adequately predicted operative risk. A unique diversion procedure described by the Bolzano group, uretero-ureterocutaneostomy, had equivalent complication rates to the more common diversion procedures. It also appears based on outcomes in this cohort that partial cystectomy is a particularly favorable option within the elderly population in terms of perioperative morbidity.

Background: We describe a multidisciplinary approach for comprehensive care of amputees with concurrent targeted muscle reinnervation (TMR) at the time of amputation., Methods: Our TMR cohort was compared to a cross-sectional sample of unselected oncologic amputees not treated at our institution (N = 58). Patient-Reported Outcomes Measurement Information System (NRS, PROMIS) were used to assess postamputation pain., Results: Thirty-one patients underwent amputation with concurrent TMR during the study; 27 patients completed pain surveys; 15 had greater than 1 year follow-up (mean follow-up 14.7 months). Neuroma symptoms occurred significantly less frequently and with less intensity among the TMR cohort. Mean differences for PROMIS pain intensity, behavior, and interference for phantom limb pain (PLP) were 5.855 (95%CI 1.159-10.55; P = .015), 5.896 (95%CI 0.492-11.30; P = .033), and 7.435 (95%CI 1.797-13.07; P = .011) respectively, with lower scores for TMR cohort. For residual limb pain, PROMIS pain intensity, behavior, and interference mean differences were 5.477 (95%CI 0.528-10.42; P = .031), 6.195 (95%CI 0.705-11.69; P = .028), and 6.816 (95%CI 1.438-12.2; P = .014), respectively. Fifty-six percent took opioids before amputation compared to 22% at 1 year postoperatively., Conclusions: Multidisciplinary care of amputees including concurrent amputation and TMR, multimodal postoperative pain management, amputee-centered rehabilitation, and peer support demonstrates reduced incidence and severity of neuroma and PLP., (© 2019 Wiley Periodicals, Inc.)

Objective: To evaluate our institutional experience of incisional negative pressure wound therapy (iNPWT) applied immediately after major limb amputation closure or amputation revision closure. Approach: A retrospective review was performed on 25 patients who underwent major limb amputation or amputation revision and had iNPWT placed intraoperatively upon incision closure. Results: Twenty-one patients underwent lower extremity amputation and four underwent upper extremity amputation. Seventeen were primary amputations and eight were amputation revisions. No patients developed dehiscence, seroma, or hematoma. One patient developed a surgical site infection (4%) that was treated with oral antibiotics. The average time to eligibility for prosthetic fitting for lower extremity amputations was 6.3 weeks. Innovation: Amputee patients have increased wound healing demands that can impact prosthetic wear and ambulation status. Stump incisions are located at the distal end of their extremities and often are in areas that have had prior surgical procedures performed. Thus, blood supply to the incision site may not be optimal. iNPWT is an effective incision management technique to promote healing and decrease postoperative complications in this patient population, which can lead to increased mortality. Conclusion: iNPWT is an effective technique of minimizing wound complications in the amputee and should be considered in this high-risk patient population.

Background: A majority of the nearly 2 million Americans living with limb loss suffer from chronic pain in the form of neuroma-related residual limb and phantom limb pain (PLP). Targeted muscle reinnervation (TMR) surgically transfers amputated nerves to nearby motor nerves for prevention of neuroma. The objective of this study was to determine whether TMR at the time of major limb amputation decreases the incidence and severity of PLP and residual limb pain., Study Design: A multi-institutional cohort study was conducted between 2012 and 2018. Fifty-one patients undergoing major limb amputation with immediate TMR were compared with 438 unselected major limb amputees. Primary outcomes included an 11-point Numerical Rating Scale (NRS) and Patient-Reported Outcomes Measurement Information System (PROMIS) pain intensity, behavior, and interference., Results: Patients who underwent TMR had less PLP and residual limb pain compared with untreated amputee controls, across all subgroups and by all measures. Median "worst pain in the past 24 hours" for the TMR cohort was 1 out of 10 compared to 5 (PLP) and 4 (residual) out of 10 in the control population (p = 0.003 and p < 0.001, respectively). Median PROMIS t-scores were lower in TMR patients for both PLP (pain intensity [36.3 vs 48.3], pain behavior [50.1 vs 56.6], and pain interference [40.7 vs 55.8]) and residual limb pain (pain intensity [30.7 vs 46.8], pain behavior [36.7 vs 57.3], and pain interference [40.7 vs 57.3]). Targeted muscle reinnervation was associated with 3.03 (PLP) and 3.92 (residual) times higher odds of decreasing pain severity compared with general amputee participants., Conclusions: Preemptive surgical intervention of amputated nerves with TMR at the time of limb loss should be strongly considered to reduce pathologic phantom limb pain and symptomatic neuroma-related residual limb pain., (Copyright © 2019. Published by Elsevier Inc.)

Objective: To determine the utility of instillation negative pressure wound therapy (NPWT) in achieving eradication of infection and definitive wound closure in patients with infected left ventricular assist device (LVAD). Approach: A retrospective review was performed in a series of patients with infected and exposed LVADs who were treated with instillation NPWT in conjunction with surgical debridement. Results: Three consecutive patients were included who developed periprosthetic infection subsequent to LVAD implantation. In all cases, the utilization of a vacuum-assisted closure with instillation (VACi) along with surgical debridement and IV antibiotics eradicated infection resulting in successful retention of hardware. Cases 1 and 2 received definitive wound closure within 3 and 12 days of starting treatment, respectively. Case 3 initially deferred surgery in favor of local wound care. Eventually the patient elected for surgical treatment and underwent closure 164 days after initial presentation. All three patients healed completely without residual evidence of infection. Flap reconstruction with a pedicled rectus flap was used to achieve definitive closure in all patients. One patient subsequently required pump replacement secondary to thrombosis and mechanical pump failure. Innovation: LVAD infections are met with high morbidity and mortality rates, and timely salvage is critical. In this initial series, VACi has proven a viable therapy option to help control and eradicate infection without LVAD removal. Conclusion: This series illustrates the value of newer techniques such as VACi in combination with surgical debridement and antibiotic therapy in effectively salvaging LVADs that were infected., Competing Interests: No competing financial interests applicable to this series. The content of this article was expressly written by the authors listed. No ghostwriters were used to write this article., (Copyright 2019, Mary Ann Liebert, Inc., publishers.)

Purpose of Review: Malnutrition in a prevalent problem in patients undergoing radical cystectomy. Preoperative malnutrition has been shown to contribute to increased rates of postoperative complications. Given the significant morbidity and mortality of the procedure of radical cystectomy, there is potential for improvement in patient outcomes by nutritional intervention., Recent Findings: Prospective studies have demonstrated a reduction in postoperative infection rates in patients who receive supplemental immunonutrition prior to major surgery including radical cystectomy. These initial evaluations of nutritional optimization show significant potential for improved outcomes. Additionally, several studies using enhanced recovery after surgery protocols, which include a preoperative nutritional component, have shown a benefit in reducing length of stay. Emerging literature has shown the benefits of preoperative immunonutrition in improving postoperative outcomes of radical cystectomy. However, further work is needed to determine the best mechanism to optimize nutrition prior to radical cystectomy.

Objective: Infection prevention in spinal surgeries involving implantation of hardware is of utmost priority. Furthermore, successful eradication of infection in hardware salvage is likewise critical in maintaining the long-term retention of the spinal hardware construct. Approach: We report a retrospective case series of three cases where the utilization of a VAC with instillation (VACi) in conjunction with surgical debridement aided in infection control and eradication for both preimplantation and hardware salvage spine patients. Results: Three patients were included. In case 1, VACi was utilized in conjunction with surgical debridement and IV antibiotics in the setting of acute preoperative infection to eradicate infection and enable necessary spinal hardware implementation. Cases 2 and 3 are representative of VACi for salvage of exposed spinal hardware in both the early and delayed infection presentation settings. In both cases, patients developed postoperative infections following spinal instrumentation VACi was utilized in conjunction with surgical debridement and IV antibiotics. Hardware removal was avoided in both cases. All three patients healed completely without residual evidence of infection. Innovation: VACi showed its effectiveness in timely infection eradication before spinal hardware instrumentation and with postoperative spine hardware salvage. Conclusion: This case series demonstrates that VACi can provide infection eradication both preoperatively in high-risk surgical sites, facilitating necessary hardware implementation and postoperatively in situations of hardware salvage.

Scientists and managers of natural resources have recognized an urgent need for improved methods and tools to enable effective adaptation of management measures in the face of climate change. This paper presents an Adaptation Design Tool that uses a structured approach to break down an otherwise overwhelming and complex process into tractable steps. The tool contains worksheets that guide users through a series of design considerations for adapting their planned management actions to be more climate-smart given changing environmental stressors. Also provided with other worksheets is a framework for brainstorming new adaptation options in response to climate threats not yet addressed in the current plan. Developed and tested in collaboration with practitioners in Hawai'i and Puerto Rico using coral reefs as a pilot ecosystem, the tool and associated reference materials consist of worksheets, instructions and lessons-learned from real-world examples. On the basis of stakeholder feedback from expert consultations during tool development, we present insights and recommendations regarding how to maximize tool efficiency, gain the greatest value from the thought process, and deal with issues of scale and uncertainty. We conclude by reflecting on how the tool advances the theory and practice of assessment and decision-making science, informs higher level strategic planning, and serves as a platform for a systematic, transparent and inclusive process to tackle the practical implications of climate change for management of natural resources.

Anesthesiologists have clearly established their place in the history of medical ethics. Our involvement goes back to 1966 when Henri Beecher published his landmark paper on research and informed consent. Participation in the ethics of transplantation is no less important than our previous work. Organ transplant has been life saving for many but also has given rise to many misunderstandings not just from the public but also among our own colleagues. These include methods of allocation and donation, the role that affluence may play in receiving an organ, the definition of death and donation after circulatory death. As perioperative physicians and important members of the transplant team, anesthesiologists are expected to participate in all aspects of care including ethical judgments. This article discusses some of the issues that seem to cause the most confusion and angst for those of us involved in both liver transplantation and in the procurement of organs. It will discuss the definition of death, donation after circulatory death, the anesthesiologists' role on the selection committee, living donor liver transplantation, and transplantation of patients with alcohol-related liver disease.

Seasonal changes in glucocorticoids and their influence on the immune system are widespread in vertebrates, but whether this occurs in lesser studied taxa like turtles is unclear. The purpose of this study was to test for seasonal changes in baseline corticosterone (CORT), innate immunity, body condition, and metabolic factors (triglycerides, uric acid) in free-ranging Eastern Box Turtles (Terrapene carolina carolina), a species which is in decline across its range. In addition, the effect of handling and confinement on CORT levels was measured. In both years of the seasonal study, baseline CORT concentrations were significantly higher in fall than in spring, but summer CORT levels differed between the years. The annual variation in CORT levels may be related to weather conditions or associated with opportunistic mating. CORT levels of turtles confined for one hour were higher than turtles bled as quickly as possible, and unlike the seasonal study, females had higher baseline and post-stressor CORT levels than males. Baseline CORT levels were positively correlated with hemolysis titer, indicating a possible immunoenhancing effect of CORT. Triglycerides were positively correlated with body condition and were higher in females than males. The higher triglyceride level in females was likely associated with the energetic demands of reproduction and nesting. Males had a lower body condition in the fall than in both spring and summer, while females exhibited no seasonal differences in body condition. Uric acid and innate immunity measures failed to exhibit significant seasonal or sex related differences. Overall our findings of substantial annual, seasonal, and sexual variation in turtle physiology are consistent with the findings reported for other vertebrates and indicate the importance of incorporating these sources of variation into the design of future studies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

N-acylethanolamine acid amidase (NAAA) is an N-terminal nucleophile (Ntn) enzyme with a catalytic cysteine residue that has highest activity at acidic pH. The most prominent substrate hydrolyzed is palmitoylethanolamine (PEA), which regulates inflammation. Inhibitors of NAAA have been shown to increase endogenous levels of PEA, and are of interest as potential treatments for inflammatory disorders and other maladies. Currently, there are no X-ray or NMR structures of NAAA available to inform medicinal chemistry. Additionally, there are a limited number of enzyme structures available that are within the Ntn-hydrolase family, have a catalytic cysteine residue, and have a high sequence homology. For these reasons, we developed expression and purification methods for the production of enzyme samples amenable to structural characterization. Mammalian cells are necessary for post-translational processing, including signal sequence cleavage and glycosylation, that are required for a correctly folded zymogen before conversion to active, and mature enzyme. We have identified an expression construct, mammalian cell line, specific media and additives to express and secrete hNAAA zymogen and we further optimized propagation conditions and show this secretion method is suitable for isotopic labeling of the protein. We refined purification methods to achieve a high degree of protein purity potentially suited to crystallography. Glycosylated proteins can present challenges to biophysical methods. Therefore we deglycosylate the enzyme and show that the activity of the mature enzyme is not affected by deglycosylation., (Published by Elsevier Inc.)

Background: The demographic of today's university student includes breastfeeding mothers. Few studies have examined the breastfeeding experience that women face upon their return to school. Research aim: The purpose of this research was to explore the breastfeeding experience of students on a university campus., Methods: This qualitative study used semistructured interviews. Responses were audiotaped, transcribed, and coded according to common themes using MAXQDA software., Results: A total of eight women were interviewed for the study. All women reported "feelings of isolation" and expressed concern over "what will others think." In addition, "nowhere to breastfeed" and "challenges of pumping" emerged as common barriers to breastfeeding. Regrettably, "forced decisions" emerged as a major theme, with four out of eight women reporting having to supplement with formula because they returned to school., Conclusion: Student breastfeeding mothers are faced with emotional and physical challenges upon their return to school. Lack of space to breastfeed or pump as well as lack of support on campus are the main reasons that students stop breastfeeding prematurely. A day care facility on campus that accepts young infants, a Baby-Friendly space, and enhanced education are required to support student mothers in their choice to breastfeed.

Geological disposal of intermediate level radioactive waste in the UK is planned to involve the use of cementitious materials, facilitating the formation of an alkali-disturbed zone within the host rock. The biogeochemical processes that will occur in this environment, and the extent to which they will impact on radionuclide migration, are currently poorly understood. This study investigates the impact of biogeochemical processes on the mobility of the radionuclide technetium, in column experiments designed to be representative of aspects of the alkali-disturbed zone. Results indicate that microbial processes were capable of inhibiting 99m Tc migration through columns, and X-ray radiography demonstrated that extensive physical changes had occurred to the material within columns where microbiological activity had been stimulated. The utilisation of organic acids under highly alkaline conditions, generating H 2 and CO 2 , may represent a mechanism by which microbial processes may alter the hydraulic conductivity of a geological environment. Column sediments were dominated by obligately alkaliphilic H 2 -oxidising bacteria, suggesting that the enrichment of these bacteria may have occurred as a result of H 2 generation during organic acid metabolism. The results from these experiments show that microorganisms are able to carry out a number of processes under highly alkaline conditions that could potentially impact on the properties of the host rock surrounding a geological disposal facility for intermediate level radioactive waste., (Copyright © 2016. Published by Elsevier B.V.)

The interactive and cumulative impacts of climate change on natural resources such as coral reefs present numerous challenges for conservation planning and management. Climate change adaptation is complex due to climate-stressor interactions across multiple spatial and temporal scales. This leaves decision makers worldwide faced with local, regional, and global-scale threats to ecosystem processes and services, occurring over time frames that require both near-term and long-term planning. Thus there is a need for structured approaches to adaptation planning that integrate existing methods for vulnerability assessment with design and evaluation of effective adaptation responses. The Corals and Climate Adaptation Planning project of the U.S. Coral Reef Task Force seeks to develop guidance for improving coral reef management through tailored application of a climate-smart approach. This approach is based on principles from a recently-published guide which provides a framework for adopting forward-looking goals, based on assessing vulnerabilities to climate change and applying a structured process to design effective adaptation strategies. Work presented in this paper includes: (1) examination of the climate-smart management cycle as it relates to coral reefs; (2) a compilation of adaptation strategies for coral reefs drawn from a comprehensive review of the literature; (3) in-depth demonstration of climate-smart design for place-based crafting of robust adaptation actions; and (4) feedback from stakeholders on the perceived usefulness of the approach. We conclude with a discussion of lessons-learned on integrating climate-smart design into real-world management planning processes and a call from stakeholders for an "adaptation design tool" that is now under development., Competing Interests: The authors declare that they have no conflict of interest.

Impacts of long-term CO 2 exposure on environmental processes and microbial populations of near-surface soils are poorly understood. This near-surface long-term CO 2 injection study demonstrated that soil microbiology and geochemistry is influenced more by seasonal parameters than elevated CO 2 Soil samples were taken during a 3-year field experiment including sampling campaigns before, during and after 24 months of continuous CO 2 injection. CO 2 concentrations within CO 2 -injected plots increased up to 23% during the injection period. No CO 2 impacts on geochemistry were detected over time. In addition, CO 2 -exposed samples did not show significant changes in microbial CO 2 and CH 4 turnover rates compared to reference samples. Likewise, no significant CO 2 -induced variations were detected for the abundance of Bacteria, Archaea (16S rDNA) and gene copy numbers of the mcrA gene, Crenarchaeota and amoA gene. The majority (75%-95%) of the bacterial sequences were assigned to five phyla: Firmicutes, Proteobacteria, Actinobacteria, Acidobacteria and Bacteroidetes The majority of the archaeal sequences (85%-100%) were assigned to the thaumarchaeotal cluster I.1b (soil group). Univariate and multivariate statistical as well as principal component analyses showed no significant CO 2 -induced variation. Instead, seasonal impacts especially temperature and precipitation were detected., (© FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The biological underpinnings and the pathological lesions of psychiatric disorders are centuries-old questions that have yet to be understood. Recent studies suggest that schizophrenia and related disorders likely have their origins in perturbed neurodevelopment and can result from a large number of common genetic variants or multiple, individually rare genetic alterations. It is thus conceivable that key neurodevelopmental pathways underline the various genetic changes and the still unknown pathological lesions in schizophrenia. Here, we report that mice defective of the nicastrin subunit of γ-secretase in oligodendrocytes have hypomyelination in the central nervous system. These mice have altered dopamine signaling and display profound abnormal phenotypes reminiscent of schizophrenia. In addition, we identify an association of the nicastrin gene with a human schizophrenia cohort. These observations implicate γ-secretase and its mediated neurodevelopmental pathways in schizophrenia and provide support for the "myelination hypothesis" of the disease. Moreover, by showing that schizophrenia and obsessive-compulsive symptoms could be modeled in animals wherein a single genetic factor is altered, our work provides a biological basis that schizophrenia with obsessive-compulsive disorder is a distinct subtype of schizophrenia., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Arsenic is a known carcinogen found in the soil in gold mining regions at concentrations thousands of times greater than gold. Mining releases arsenic into the environment and surrounding water bodies. The main chemical forms of arsenic found in the environment are inorganic arsenite (As(III)) and arsenate (As(V)). Yabbies (Cherax destructor) accumulate arsenic at levels comparable to those in the sediment of their environment but the effect on their physiological function is not known. The effects of arsenic exposure (10 ppm sodium arsenite, AsNaO2 - 5.7 ppm As(III)) and 10 ppm arsenic acid, Na2HAsO4·7H2O - 2.6 ppm As(V)) for 40 days on the contractile function of the two major fibre types from the chelae were determined. After exposure, individual fibres were isolated from the chela, "skinned" (membrane removed) and attached to the force recording apparatus. Contraction was induced in solutions containing increasing [Ca(2+)] until a maximum Ca(2+)-activation was obtained. Submaximal force responses were plotted as a percentage of the maximum Ca(2+)-activated force. As(V) exposure resulted in lower levels of calcium required for activation than As(III) indicating an increased sensitivity to Ca(2+) after long term exposure to arsenate compared to arsenite. Myosin heavy chain and tropomyosin content in individual fibres was also decreased as a result of arsenic exposure. Single fibres exposed to As(V) produced significantly more force than muscle fibres from control animals. Long-term exposure of yabbies to arsenic alters the contractile function of the two major fibre types in the chelae., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction: Numerous surgical techniques have been described to facilitate closure of the renal parenchymal defect. We sought to describe the operative technique and define the safety and efficacy of using an expanded polytetrafluoroethylene (GORE-TEX; WL Gore and Associates, Flagstaff, AZ) bolster to aid in closure of the renal parenchymal defect at the time of open partial nephrectomy (OPN)., Technical Considerations: A retrospective review of 175 patients who underwent an OPN using an expanded polytetrafluoroethylene (ePTFE) bolster at the Huntsman Cancer Hospital, University of Utah and Salt Lake City Veterans Affairs Medical Center from March 2005 to February 2013 was conducted. Postoperative complications occurring within 90 days were graded using the Clavien grading system., Conclusion: Overall, 57 patients (32.6%) experienced a postoperative complication. Fifteen patients (8.5%) had a Clavien ≥ grade-III complication. Ten patients (5.7%) received blood transfusions. Urine leak requiring intervention occurred in 2 patients (1.1%). Delayed hemorrhage requiring nephrectomy and pseudoaneurysm formation were rare, occurring in 1 patient each (0.6%). Infection of the ePTFE material occurred in 2 patients (1.1%). In both cases, it was explanted without requiring nephrectomy. The use of an ePTFE bolster is an effective and safe method of closing the renal parenchymal defect after OPN with an acceptable 90-day postoperative complication rate and a low risk of infection., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: We compared the outcomes of various adult continent catheterizable channels in a multi-institutional setting., Materials and Methods: We retrospectively reviewed the records of all adults who underwent construction of a continent catheterizable channel at our 4 institutions from 2004 to 2013 and who had at least 6 months of followup. Patients were stratified by channel type, including continent cutaneous ileal cecocystoplasty or tunneled cutaneous channel, eg appendicovesicostomy, Monti channel, etc. The primary study outcome was the need for a secondary procedure to correct stomal leakage, catheterizable channel obstruction or stomal stenosis. Secondary outcomes were patient reported leakage and 30-day postoperative complications. We used Firth logistic regression to control for the heterogeneity induced by multiple institutions., Results: A total of 61 patients were included in study, of whom 31 underwent continent cutaneous ileal cecocystoplasty. Mean age was 41.4 years (range 22 to 76). Median followup was 16 months. More patients with a tunneled channel required a secondary procedure than those with cecocystoplasty (15 of 30 or 50% vs 4 of 31 or 13%, OR 6.4, 95% CI 1.8-28). The total number of required secondary procedures was also greater for tunneled channels than for cecocystoplasty (27 vs 4). Of patients with cecocystoplasty 29% reported stomal leakage compared with 43% of those with a tunneled channel (p = 0.12). A high rate of postoperative complications was observed regardless of technique, including 40% for channels and 51.7% for cecocystoplasty., Conclusions: Patients with continent cutaneous ileal cecocystoplasty undergo fewer interventions to maintain the catheterizable channel than patients with a tunneled continent catheterizable channel., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)