The productivity-stability trade-off in global food systems.

Historically, humans have managed food systems to maximize productivity. This pursuit has drastically modified terrestrial and aquatic ecosystems globally by reducing species diversity and body size while creating very productive, yet homogenized, environments. Such changes alter the structure and function of ecosystems in ways that ultimately erode their stability. This productivity-stability trade-off has largely been ignored in discussions around global food security. Here, we synthesize empirical and theoretical literature to demonstrate the existence of the productivity-stability trade-off and argue the need for its explicit incorporation in the sustainable management of food systems. We first explore the history of human management of food systems, its impacts on average body size within and across species and food web stability. We then demonstrate how reductions in body size are symptomatic of a broader biotic homogenization and rewiring of food webs. We show how this biotic homogenization decompartmentalizes interactions among energy channels and increases energy flux within the food web in ways that threaten their stability. We end by synthesizing large-scale ecological studies to demonstrate the prevalence of the productivity-stability trade-off. We conclude that management strategies promoting landscape heterogeneity and maintenance of key food web structures are critical to sustainable food production.

Using the role model approach to optimise caregiver administration of sulfadoxine-pyrimethamine amodiaquine to children aged 3-59 months in Burkina Faso, Chad and Togo: findings from an evaluation.

BACKGROUND: Seasonal malaria chemoprevention (SMC) is a World Health Organization-recommended intervention for the prevention of malaria among children at high risk in areas with seasonal transmission. During the coronavirus disease 2019 (COVID-19) pandemic, SMC drug distribution was rapidly adapted to reduce contact and mitigate the risk of transmission between communities and community distributors, with caregivers administering doses. To address the challenges and find local solutions to improve administration and adherence, the role model approach was designed, implemented and evaluated in selected communities of Burkina Faso, Chad and Togo. This paper describes the results of this evaluation. METHODS: Focus group discussions were held with primary caregivers in all three countries to understand their perceptions of the approach's acceptability and feasibility. In Burkina Faso and Togo, household surveys assessed the characteristics of caregivers reached by role model activities. Key indicators on SMC coverage and adherence allowed for an assessment of caregiver engagement outcomes related to participation in activities. Statistical associations between participation in study's activities and caregiver beliefs related to SMC had been tested. RESULTS: The majority of caregivers believed the approach to have a positive effect on drug administration, with most adopting the promoted strategies. Greater involvement of fathers in drug administration and acknowledgement of their joint responsibility was a notable positive outcome. However, several barriers to participation were noted and there was criticism of the group approach. In Burkina Faso and Togo, end-of-round survey results revealed that 98.4% of respondents agreed the approach improved their knowledge and skills in malaria prevention, while 100% expressed a desire to continue practicing the behaviours learned. However, there was a relatively low level of awareness of the approach among communities. Participation was strongly associated with participants' self-reported belief in ease of remembering to administer, and ease of administering, SMC medicines. CONCLUSION: Caregivers perceived the role model approach to be beneficial in aiding drug administration, with other positive impacts also reported. Replication and scale-up should utilize the most popular communication channels and existing community structures to ensure activities are promoted effectively. A mixture of group and one-on-one approaches should be used where appropriate and feasible.

Evidence for inflammation in normal-appearing brain regions in patients with growing sporadic vestibular schwannoma: A PET study.

Background: Nonauditory symptoms can be a prominent feature in patients with sporadic vestibular schwannoma (VS), but the cause of these symptoms is unknown. Inflammation is hypothesized to play a key role in the growth and symptomatic presentation of sporadic VS, and in this study, we investigated through translocator protein (TSPO) positron emission tomography (PET) whether inflammation occurred within the "normal appearing" brain of such patients and its association with tumor growth. Methods: Dynamic PET datasets from 15 patients with sporadic VS (8 static and 7 growing) who had been previously imaged using the TSPO tracer [11C](R)-PK11195 were included. Parametric images of [11C](R)-PK11195 binding potential (BPND) and the distribution volume ratio (DVR) were derived and compared across VS growth groups within both contralateral and ipsilateral gray (GM) and white matter (WM) regions. Voxel-wise cluster analysis was additionally performed to identify anatomical regions of increased [11C](R)-PK11195 binding. Results: Compared with static tumors, growing VS demonstrated significantly higher cortical (GM, 1.070 vs. 1.031, P = .03) and whole brain (GM & WM, 1.045 vs. 1.006, P = .03) [11C](R)-PK11195 DVR values. The voxel-wise analysis supported the region-based analysis and revealed clusters of high TSPO binding within the precentral, postcentral, and prefrontal cortex in patients with growing VS. Conclusions: We present the first in vivo evidence of increased TSPO expression and inflammation within the brains of patients with growing sporadic VS. These results provide a potential mechanistic insight into the development of nonauditory symptoms in these patients and highlight the need for further studies interrogating the role of neuroinflammation in driving VS symptomatology.

Venous thromboembolism chemical prophylaxis after skull base surgery.

PURPOSE: There is no guidance surrounding postoperative venous thromboembolism (VTE) prophylaxis using pharmacological agents (chemoprophylaxis) in patients undergoing skull base surgery. The aim of this study was to compare VTE and intracranial haematoma rates after skull base surgery in patients treated with/without chemoprophylaxis. METHODS: Review of prospective quaternary centre database including adults undergoing first-time skull base surgery (2009-2020). VTE was defined as deep vein thrombosis (DVT) and pulmonary embolism (PE) within 6 months of surgery. Multivariate logistic regression was used to determine factors predictive of postoperative intracranial haematoma/VTE. Propensity score matching (PSM) was used in group comparisons. RESULTS: One thousand five hundred fifty-one patients were included with a median age of 52 years (range 16-89 years) and female predominance (62%). Postoperative chemoprophylaxis was used in 81% of patients at a median of 1 day postoperatively. There were 12 VTE events (1.2%), and the use of chemoprophylaxis did not negate the risk of VTE entirely (p > 0.99) and was highest on/after postoperative day 6 (9/12 VTE events). There were 18 intracranial haematomas (0.8%), and after PSM, chemoprophylaxis did not significantly increase the risk of an intracranial haematoma (p > 0.99). Patients administered chemoprophylaxis from postoperative days 1 and 2 had similar rates of intracranial haematomas (p = 0.60) and VTE (p = 0.60), affirmed in PSM. CONCLUSION: Postoperative chemoprophylaxis represents a relatively safe strategy in patients undergoing skull base surgery. We advocate a personalised approach to chemoprophylaxis and recommend it on postoperative days 1 or 2 when indicated.

Improved Recovery after Vestibular Schwannoma Excision with Intratympanic Gentamicin Prehabilitation.

OBJECTIVE: Translabyrinthine excision of a vestibular schwannoma is associated with acute vestibular failure. Preoperative intratympanic gentamicin (ITG) injections can improve objective balance function after surgery but its clinical benefits remain to be established. METHODS: Adult patients undergoing translabyrinthine removal of a vestibular schwannoma between January 2014 and February 2018 underwent preoperative vestibular function testing. Patients were divided in to 3 groups, those with vestibular function (VF) who received ITG injections, those with VF but did not receive ITG and those with no VF. Groups were compared according to degree of vertigo, length of stay, time to unassisted mobilization, and postoperative anti-emetic consumption. RESULTS: Forty six patients had ITG injections (Group 1), 7 had residual VF but refused treatment (Group 2), 21 had no VF (Group 3). Group 1 had a significant improvement in vertigo over time whereas groups 2 and 3 did not. There was a statistically significant 70% decrease in time to independent mobilization between Group 1 and other groups and a 19% decrease in length of stay in Group 1 compared to other groups although this did not reach statistical significance. Two patients had injection-related complications. Group 1 used less anti-emetics than other groups but this was not statistically significant. CONCLUSION: Preoperative intratympanic gentamicin injection with vestibular rehabilitation exercises is associated with less postoperative vertigo and earlier postoperative mobilization. There was reduced duration of hospitalization and decreased consumption of anti-emetic but not significantly so possibly because of low numbers of patients in the no treatment group. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:3316-3322, 2024.

Changes in audiovestibular handicap following treatment of vestibular schwannomas.

OBJECTIVE: This study aimed to assess degree of audiovestibular handicap in patients with vestibular schwannoma. METHODS: Audiovestibular handicap was assessed using the Hearing Handicap Inventory, Tinnitus Handicap Inventory and Dizziness Handicap Inventory. Patients completed questionnaires at presentation and at least one year following treatment with microsurgery, stereotactic radiosurgery or observation. Changes in audiovestibular handicap and factors affecting audiovestibular handicap were assessed. RESULTS: All handicap scores increased at follow up, but not significantly. The Tinnitus Handicap Inventory and Dizziness Handicap Inventory scores predicted tinnitus and dizziness respectively. The Hearing Handicap Inventory was not predictive of hearing loss. Age predicted Tinnitus Handicap Inventory score and microsurgery was associated with a deterioration in Dizziness Handicap Inventory score. CONCLUSION: Audiovestibular handicap is common in patients with vestibular schwannoma, with 75 per cent having some degree of handicap in at least one inventory. The overall burden of handicap was, however, low. The increased audiovestibular handicap over time was not statistically significant, irrespective of treatment modality.

The management of symptomatic hyperostotic bilateral spheno-orbital meningiomas: patient series.

BACKGROUND: The occurrence of hyperostotic bilateral spheno-orbital meningiomas (BSOMs) is very rare. Patients present with bilateral symptoms and require bilateral treatment. This series describes 6 patients presenting to 2 UK neurosurgical units and includes a literature review. To the best of the authors' knowledge, this is the largest series documented. OBSERVATIONS: This is a retrospective review of patients with BSOMs presenting between 2006 and 2023. Six females, whose mean age was 43 (range: 36-64) years, presented with features of visual disturbance. Bilateral sphen-oorbital meningiomas were identified. All patients underwent bilateral staged resections. The patients had an initial improvement in their symptoms. Extensive genetic testing was performed in 4 patients, with no variants in the NF2, LZTR1, SMARCB1, SMARCE1, and SMARCA4 genes or other variants detected. The mean follow-up was 100.3 (range: 64-186) months. Sixty-seven percent of patients had good long-term visual acuity. The progression rate was 75% and was particularly aggressive in 1 patient. Four patients required radiation therapy, and 2 needed further surgery. LESSONS: Hyperostotic BSOMs are extensive, challenging tumors causing significant disability. They can recur, with significant patient impact. Multidisciplinary management and indefinite long-term follow-up are essential. The biology of these tumors remains unclear. As molecular testing expands, the understanding of BSOM oncogenesis and potential therapeutic targets is likely to improve.

Impact of the COVID-19 pandemic on care disruptions, outcomes, and costs in patients receiving pulmonary arterial hypertension-specific therapy in the United States of America: An observational study.

Regular expert follow-up, risk assessment, and early therapeutic intervention minimize worsening of pulmonary arterial hypertension (PAH). COVID-19 lockdown measures were challenging for chronic disease management. This retrospective, longitudinal analysis used US claims data (January 12, 2016 to September 11, 2021) for patients treated with PAH-specific medication to compare in-person outpatient and specialist visits, telemedicine visits, and PAH-related tests during 6-month assessment periods pre- and immediately post-COVID-19. Hospitalizations, costs, and outcomes were compared in patients with and without care disruptions (no in-person or telemedicine outpatient visits in immediate post-COVID-19 period). Patients in the immediate post-COVID-19 (N = 599) versus the pre-COVID-19 period (N = 598) had fewer in-person outpatient visits (mean 1.27 vs. 2.12) and in-person specialist visits (pulmonologist, 22.9% vs. 37.0% of patients; cardiologist, 27.5% vs. 33.8%); and more telemedicine visits (mean 0.45 vs. 0.02). In the immediate post-COVID-19 period, patients were less likely to have a PAH-related test versus the pre-COVID-19 period (incidence rate ratio: 0.700; 95% confidence interval: 0.615-0.797), including electrocardiograms (41.7% vs. 54.2%) and 6-minute walk distance tests (16.2% vs. 24.9%). In the immediate post-COVID-19 period, 48 patients had care disruptions and, in the following year, required more hospital days than those without care disruptions (N = 240) (median 10 vs. 5 days in total) and had higher overall hospitalization costs (median US$34,755 vs. US$20,090). Our findings support the need for minimizing care disruptions to potentially avoid incremental post-disruption healthcare utilization and costs among patients with serious chronic diseases such as PAH.

Surgery versus radiosurgery for vestibular schwannoma: Shared decision making in a multidisciplinary clinic.

Background: Our neurosurgical unit adopted a model of shared decision-making (SDM) based on multidisciplinary clinics for vestibular schwannoma (VS). A unique feature of this clinic is the interdisciplinary counseling process with a surgeon presenting the option of surgery, an oncologist radiosurgery or radiotherapy, and a specialist nurse advocating for the patient. Methods: This is a retrospective cohort study. All new patients seen in the combined VS clinic and referred from the skull base multidisciplinary team (MDT) from beginning of June 2013 to end of January 2019 were included. Descriptive statistics and frequency analysis were carried out for the full cohort. Results: Three hundred and fifty-four patients presenting with new or previously untreated VS were included in the analysis. In our cohort, roughly one-third of patients fall into each of the treatment strategies with slightly smaller numbers of patients undergoing surgery than watch, wait and rescan (WWR) ,and SRS (26.6% vs. 32.8% and 37.9%, respectively). Conclusion: In our experience, the combined surgery/oncology/specialist nurse clinic streamlines the patient experience for those with a VS suitable for either microsurgical or SRS/radiotherapy treatment. Decision-making in this population of patients is complex and when presented with all treatment options patients do not necessarily choose the least invasive option as a treatment. The unique feature of our clinic is the multidisciplinary counseling process with a specialist nurse advocating and guiding the patient. Treatment options are likely to become more rather than less complex in future years making combined clinics more valuable than ever in the SDM process.

The clinical, genetic, and immune landscape of meningioma in patients with NF2-schwannomatosis.

NF2-schwannomatosis is the most common genetic predisposition syndrome associated with meningioma. Meningioma in NF2-schwannomatosis is a major source of morbidity and mortality. This is due to accumulative tumor burden in patients with synchronous schwannomas and ependymomas, sometimes including complex collision tumors. Balancing the impact of multiple interventions against the natural history of various index tumors, and the ongoing risk of de novo tumors over an individual's lifetime makes decision-making complex. The management of any given individual meningioma is often different from a comparable sporadic tumor. There is typically a greater emphasis on conservative management and tolerating growth until a risk boundary is reached, whereby symptomatic deterioration or higher risk from anticipated future treatment is threatened. Management by high-volume multidisciplinary teams improves quality of life and life expectancy. Surgery remains the mainstay treatment for symptomatic and rapidly enlarging meningioma. Radiotherapy has an important role but carries a higher risk compared to its use in sporadic disease. Whilst bevacizumab is effective in NF2-associated schwannoma and cystic ependymoma, it has no value in the management of meningioma. In this review, we describe the natural history of the disease, underlying genetic, molecular, and immune microenvironment changes, current management paradigms, and potential therapeutic targets.

Does tumoral cavernous carotid stenosis predict an increased risk of future stroke in skull base meningiomas?

OBJECTIVE: Skull base meningiomas (SBMs) involving the cavernous sinus encase the internal carotid artery (ICA) and may lead to stenosis of the vessel. Although ischemic stroke has been reported in the literature, there are to the authors' knowledge no reported studies quantifying the risk of stroke in these patients. The authors aimed to determine the frequency of arterial stenosis in patients with SBMs that encase the cavernous ICA and to estimate the risk of ischemic stroke in these patients. METHODS: Records of all patients with SBM encasing the ICA whose cases were managed by the skull base multidisciplinary team at Salford Royal Hospital between 2011 and 2017 were reviewed using a two-stage approach: 1) clinical and radiological strokes were identified from electronic patient records, and 2) cases were reviewed to examine the correlation between ICA stenosis associated with SBM encasement and anatomically related stroke. Strokes that were caused by another pathology or did not occur in the perfusion territory were excluded. RESULTS: In the review of patient records the authors identified 118 patients with SBMs encasing the ICA. Of these, 62 SBMs caused stenosis. The median age at diagnosis was 70 (IQR 24) years, and 70% of the patients were female. The median follow-up was 97 (IQR 101) months. A total of 13 strokes were identified in these patients; however, only 1 case of stroke was associated with SBM encasement, which occurred in the perfusion territory of a patient without stenosis. Risk of acute stroke during the follow-up period for the entire cohort was 0.85%. CONCLUSIONS: Acute stroke in patients with ICA encasement by SBMs is rare despite the propensity of these tumors to stenose the ICA. Patients with ICA stenosis secondary to their SBM did not have a higher incidence of stroke than those with ICA encasement without stenosis. The results of this study demonstrate that prophylactic intervention to prevent stroke is not necessary in ICA stenosis secondary to SBM.

Radiation treatment of benign tumors in NF2-related-schwannomatosis: A national study of 266 irradiated patients showing a significant increase in malignancy/malignant progression.

Background: Radiation treatment of benign tumors in tumor predisposition syndromes is controversial, but short-term studies from treatment centers suggest safety despite apparent radiation-associated malignancy being reported. We determined whether radiation treatment in NF2-related schwannomatosis patients is associated with increased rates of subsequent malignancy (M)/malignant progression (MP). Methods: All UK patients with NF2 were eligible if they had a clinical/molecular diagnosis. Cases were NF2 patients treated with radiation for benign tumors. Controls were matched for treatment location with surgical/medical treatments based on age and year of treatment. Prospective data collection began in 1990 with addition of retrospective cases in 1969. Kaplan-Meier analysis was performed for malignancy incidence and survival. Outcomes were central nervous system (CNS) M/MP (2cm annualized diameter growth) and survival from index tumor treatment. Results: In total, 1345 NF2 patients, 266 (133-Male) underwent radiation treatments between 1969 and 2021 with median first radiotherapy age of 32.9 (IQR = 22.4-46.0). Nine subsequent CNS malignancies/MPs were identified in cases with only 4 in 1079 untreated (P < .001). Lifetime and 20-year CNS M/MP was ~6% in all irradiated patients-(4.9% for vestibular schwannomas [VS] radiotherapy) versus <1% in the non-irradiated population (P < .001/.01). Controls were well matched for age at NF2 diagnosis and treatment (Males = 133%-50%) and had no M/MP in the CNS post-index tumor treatment (P = .0016). Thirty-year survival from index tumor treatment was 45.62% (95% CI = 34.0-56.5) for cases and 66.4% (57.3-74.0) for controls (P = .02), but was nonsignificantly worse for VS radiotherapy. Conclusion: NF2 patients should not be offered radiotherapy as first-line treatment of benign tumors and should be given a frank discussion of the potential 5% excess absolute risk of M/MP.

Intraoperative diagnosis of facial schwannomas: a multicenter summation of clinical experience, preoperative avoidance, and intraoperative management protocol.

OBJECTIVE: Preoperative differentiation of facial nerve schwannoma (FNS) from vestibular schwannoma (VS) can be challenging, and failure to differentiate between these two pathologies can result in potentially avoidable facial nerve injury. This study presents the combined experience of two high-volume centers in the management of intraoperatively diagnosed FNSs. The authors highlight clinical and imaging features that can distinguish FNS from VS and provide an algorithm to help manage intraoperatively diagnosed FNS. METHODS: Operative records of 1484 presumed sporadic VS resections between January 2012 and December 2021 were reviewed, and patients with intraoperatively diagnosed FNSs were identified. Clinical data and preoperative imaging were retrospectively reviewed for features suggestive of FNS, and factors associated with good postoperative facial nerve function (House-Brackmann [HB] grade ≤ 2) were identified. A preoperative imaging protocol for suspected VS and recommendations for surgical decision-making following an intraoperative FNS diagnosis were created. RESULTS: Nineteen patients (1.3%) with FNSs were identified. All patients had normal facial motor function preoperatively. In 12 patients (63%), preoperative imaging demonstrated no features suggestive of FNS, with the remainder showing subtle enhancement of the geniculate/labyrinthine facial segment, widening/erosion of the fallopian canal, or multiple tumor nodules in retrospect. Eleven (57.9%) of the 19 patients underwent a retrosigmoid craniotomy, and in the remaining patients, a translabyrinthine (n = 6) or transotic (n = 2) approach was used. Following FNS diagnosis, 6 (32%) of the tumors underwent gross-total resection (GTR) and cable nerve grafting, 6 (32%) underwent subtotal resection (STR) and bony decompression of the meatal facial nerve segment, and 7 (36%) underwent bony decompression only. All patients undergoing subtotal debulking or bony decompression exhibited normal postoperative facial function (HB grade I). At the last clinical follow-up, patients who underwent GTR with a facial nerve graft had HB grade III (3 of 6 patients) or IV facial function. Tumor recurrence/regrowth occurred in 3 patients (16%), all of whom had been treated with either bony decompression or STR. CONCLUSIONS: Intraoperative diagnosis of an FNS during a presumed VS resection is rare, but its incidence can be reduced further by maintaining a high index of suspicion and undertaking further imaging in patients with atypical clinical or imaging features. If an intraoperative diagnosis does occur, conservative surgical management with bony decompression of the facial nerve only is recommended, unless there is significant mass effect on surrounding structures.

Increased Circulating Chemokines and Macrophage Recruitment in Growing Vestibular Schwannomas.

BACKGROUND: There is evidence that macrophage infiltration in the tumor microenvironment promotes vestibular schwannoma (VS) growth. Efficacy of bevacizumab in NF2-associated VS demonstrates the value of therapies targeting the microvascular tumor microenvironment, and tumor-associated macrophages (TAMs) may represent another druggable target. OBJECTIVE: To characterize the relationship between growth, TAM infiltration, and circulating monocyte chemokines in a large cohort of patients with VS. METHODS: Immunostaining for Iba1 (macrophages), CD31 (endothelium), and fibrinogen (permeability) was performed on 101 growing and 19 static sporadic VS. The concentrations of monocyte-specific chemokines were measured in the plasma of 50 patients with growing VS and 25 patients with static VS. RESULTS: The Iba1 + cell count was significantly higher in growing as compared with static VS (592 vs 226/×20 HPF, P =<0.001). Similarly, the CD31 + % surface area was higher in growing VS (2.19% vs 1.32%, P = .01). There was a positive correlation between TAM infiltration and VS growth rate, which persisted after controlling for the effect of tumor volume (aR2 = 0.263, P =<0.001). The plasma concentrations of several monocytic chemokines were higher in patients with growing rather than static VS. CONCLUSION: There is a strong positive correlation between TAM infiltration and volumetric growth of VS, and this relationship is independent of tumor size. There is a colinear relationship between TAM infiltration and tumor vascularity, implying that inflammation and angiogenesis are interlinked in VS. Chemokines known to induce monocyte chemotaxis are found in higher concentrations in patients with growing VS, suggestive of a potential pathophysiological mechanism.

Managing aquatic habitat structure for resilient trophic interactions.

Structural habitat (the three-dimensional arrangement of physical matter, abiotic and biotic, at a location) is a foundational element for the resilience and maintenance of biodiversity, yet anthropogenic development is driving the global simplification of aquatic environments. Resource managers regularly seek to conserve aquatic food webs by increasing structural habitat complexity with expected benefits to fisheries; however, the global effectiveness of such actions is unclear. Our synthesis and theoretical analyses found that the response of a consumer-resource interaction (predatory sportfish and forage fish prey) to the addition of prey refuge habitat differed among systems with low and high rates of biomass transfer from resource to consumer (i.e., biomass potential); stabilization was not the rule. Greater prey refuge habitat availability tended to stabilize systems characterized by high biomass potential while simultaneously increasing consumer densities. In contrast, increasing prey refuge habitat availability in systems characterized by low biomass potential tended to mute energy transfer and moved consumer densities toward local extinction. Importantly, biomass potential and prey refuge can have antagonistic effects on stability and relative consumer densities, and it is therefore important to consider the local conditions of a system when using habitat manipulation as a management measure. Further development of our context-dependent perspective to whole food webs, and across different environments, may help to guide structural habitat management to better restore and protect aquatic ecosystems.

Optimizing the role of 'lead mothers' in seasonal malaria chemoprevention (SMC) campaigns: formative research in Kano State, northern Nigeria.

BACKGROUND: Seasonal malaria chemoprevention (SMC) is a safe and effective intervention for preventing malaria in children under 5 years of age. Lead mothers are community health volunteers that help caregivers comply with monthly administration of anti-malarial drugs during SMC campaigns. The lead mother approach is used in several SMC implementing states across Nigeria, but there is lack of evidence about their roles and how effective they are. This study sought to better understand the current role of lead mothers, identify areas for improvement and ways to optimize the role of lead mothers during SMC campaigns. METHODS: This paper reports the formative phase of a three-phased intervention development study. The formative phase involved semi-structured interviews with stakeholders from national, state, local government and community levels (n = 20). Thematic analysis was used to identify key themes, forming the basis of a subsequent co-design workshop with stakeholders routinely involved in SMC campaigns. RESULTS: The findings of the formative phase converged around four overarching themes: skills and attributes required of lead mothers; factors that affect lead mother's roles; how lead mothers interact with Community Health Influencers Promoters Services (CHIPS) agents and re-imagining the role of lead mothers during SMC campaigns. CONCLUSION: This formative work in Kano state indicates that through their strong connection to communities and unique relationship with caregivers, lead mothers can and do influence caregivers to adopt healthy behaviours during SMC campaigns. However, there is room for improvement in how they are recruited, trained and supervised. There is need to improve lead mothers' knowledge and skills through adequate training and supporting materials, so they can deliver targeted health messages to caregivers. Sustainability of the lead mother approach is at risk if policymakers do not find a way of transitioning their role into the existing community health worker infrastructure, for example by using CHIPs agents, and ensuring less reliance on external donor support.

Genome-wide association analysis identifies a susceptibility locus for sporadic vestibular schwannoma at 9p21.

Vestibular schwannomas are benign nerve sheath tumours that arise on the vestibulocochlear nerves. Vestibular schwannomas are known to occur in the context of tumour predisposition syndromes NF2-related and LZTR1-related schwannomatosis. However, the majority of vestibular schwannomas present sporadically without identification of germline pathogenic variants. To identify novel genetic associations with risk of vestibular schwannoma development, we conducted a genome-wide association study in a cohort of 911 sporadic vestibular schwannoma cases collated from the neurofibromatosis type 2 genetic testing service in the north-west of England, UK and 5500 control samples from the UK Biobank resource. One risk locus reached genome-wide significance in our association analysis (9p21.3, rs1556516, P = 1.47 × 10-13, odds ratio = 0.67, allele frequency = 0.52). 9p21.3 is a genome-wide association study association hotspot, and a number of genes are localized to this region, notably CDKN2B-AS1 and CDKN2A/B, also referred to as the INK4 locus. Dysregulation of gene products within the INK4 locus have been associated with multiple pathologies and the genes in this region have been observed to directly impact the expression of one another. Recurrent associations of the INK4 locus with components of well-described oncogenic pathways provides compelling evidence that the 9p21.3 region is truly associated with risk of vestibular schwannoma tumorigenesis.

Smokefree and vapefree streets: high levels of support from tourists, residents and businesses, implications for tourist-destination communities in New Zealand.

AIMS: To (a) evaluate the attitudes of local businesses, residents, and visitors regarding the trial of a voluntary smokefree and vapefree zone covering the central business streets of a popular tourist town in the South Island of New Zealand, and (b) observe smoking and vaping prevalence before and during the trial, to inform national and local smokefree environment advocacy work. METHODS: The six-month smokefree and vapefree trial included an embedded mixed methods project evaluation to capture a range of stakeholder groups' views about the smokefree and vapefree zone. Data collection methods included face-to-face interviews, non-random pen and paper and online surveys, and observational scans. Qualitative data were analysed using a systematic iterative thematic approach, and simple descriptive quantitative analyses were applied to the survey data. RESULTS: The analysis synthesised information from almost 1,000 respondents. A large majority of respondents supported smokefree and vapefree within the zone (visitors 84%; residents 67%; businesses 63%). A majority of responding visitors indicated that the same rules should apply to both smoking and vaping and that they would be either more likely or as likely to visit other tourist destinations in New Zealand if they had smokefree and vapefree zones. Implementing the initiative was associated with a reduction in the number of people visibly smoking and vaping within the zone. CONCLUSION: The weight of evidence from the project evaluation points towards a net benefit both for individuals and for the community from implementing voluntary smokefree and vapefree zones in tourist destinations in New Zealand.

Co-implementing vitamin A supplementation with seasonal malaria chemoprevention in Sokoto State, Nigeria: a feasibility and acceptability study.

BACKGROUND: Bi-annual high dose vitamin A supplements administered to children aged 6-59 months can significantly reduce child mortality, but vitamin A supplementation (VAS) coverage is low in Nigeria. The World Health Organization recommends that VAS be integrated into other public health programmes which are aimed at improving child survival. Seasonal malaria chemoprevention (SMC) provides a ready platform for VAS integration to improve health outcomes. This study explored the feasibility and acceptability of integrating VAS with SMC in one local government area in Sokoto State. METHODS: A concurrent QUAN-QUAL mixed methods study was used to assess the feasibility and acceptability of co-implementing VAS with SMC in one LGA of Sokoto state. Existing SMC implementation tools and job aids were revised and SMC and VAS were delivered using a door-to-door approach. VAS and SMC coverage were subsequently assessed using questionnaires administered to 188 and 197 households at baseline and endline respectively. The qualitative component involved key informant interviews and focus group discussions with policymakers, programme officials and technical partners to explore feasibility and acceptability. Thematic analysis was carried out on the qualitative data. RESULTS: At endline, the proportion of children who received at least one dose of VAS in the last six months increased significantly from 2 to 59% (p < 0.001). There were no adverse effects on the coverage of SMC delivery with 70% eligible children reached at baseline, increasing to 76% (p = 0.412) at endline. There was no significant change (p = 0.264) in the quality of SMC, measured by proportion of children receiving their first dose as directly observed treatment (DOT), at baseline (54%) compared to endline (68%). The qualitative findings are presented as two overarching themes relating to feasibility and acceptability of the integrated VAS-SMC strategy, and within each, a series of sub-themes describe study participants' views of important considerations in implementing the strategy. CONCLUSION: This study showed that it is feasible and acceptable to integrate VAS with SMC delivery in areas of high seasonal malaria transmission such as northern Nigeria, where SMC campaigns are implemented. SMC-VAS integrated campaigns can significantly increase vitamin A coverage but more research is required to demonstrate the feasibility of this integration in different settings and on a larger scale.

Long-Term Outcomes of the Electrically Unresponsive, Anatomically Intact Facial Nerve Following Vestibular Schwannoma Surgery.

Objective The study aimed to determine long-term outcomes in patients with intraoperative electrical conduction block in an anatomically intact facial nerve (FN). Methods Single center retrospective review of prospectively collected database of all vestibular schwannoma surgeries between January 1, 2008 and August 25, 2015. Operative notes were reviewed and patients with anatomically intact FNs, but complete conduction block at the end of surgery were included for analysis. Results In total, 371 patients had vestibular schwannoma surgery of which 18 met inclusion criteria. Mean follow-up was 34.28 months and average tumor size was 28.00 mm. Seventeen patients had House-Brackmann Grade VI facial palsy immediately postoperatively and one patient was grade V. At 1 year, three patients remained grade VI (17%), two improved to grade V (11%), seven to grade IV (39%), six to grade III (33%), and one patient to grade II (6%). On extended follow-up, five patients (28%) had additional 1 to 2 score improvement in facial function. Subset analysis revealed no correlation of tumor size, vascularity, adherence to nerve, operative approach, extent of resection, splaying of FN, and recurrent tumor or sporadic tumors to the extent of FN recovery. Conclusion Intraoperative conduction block does not condemn a patient to permanent FN palsy. There is potential for a degree of recovery comparable with those undergoing nerve grafting. Our data do not clearly support a policy of same-surgery or early-postoperative primary nerve grafting in the event of a complete conduction block, and instead we favor monitoring for recovery in an anatomically intact nerve.