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In 2013, the Collaborative Crop Research Program (McKnight Foundation), initiated support for farmer research networks (FRNs). FRNs were envisaged as a general approach to networked participatory research aimed at supporting the agroecological intensification (AEI) of smallholder farming in ten countries in Africa and the Andes region in South America. The 30 FRNs ranged in size from 15 to more than 2,000 farmers. Rather than imposing a rigid FRN model, the programme used principles to guide action and reflection. The principles concerned ways of working with farmers, conducting research, and networking. This approach made it possible to reflect on how principles were interpreted, implemented, and used to guide learning in different contexts. This paper reports on insights gained from facilitated learning from 2013–2019 and focuses on subsets of diverse FRNs. Of the 30 FRNs supported, four were analyzed at some depth, reports and interviews were analyzed for 16, and a survey was conducted for 21. Relying on principles rather than an operational model has allowed for their progressive application, as participatory processes, farmer engagement, organizational capital, trust, and networks are built. Any reduced clarity and coherence seem outweighed by greater adaptability to context and resulting creativity.

In situ measurements have suggested vehicle emissions may dominate agricultural sources of NH3 in many cities, which is alarming given the potential for urban NH3 to significantly increase human ex...

BACKGROUND AND PURPOSE The aim of this study was to identify the long-term radiological changes, autoantibody specificities, and clinical course in a patient with kelch-like protein 11 (KLHL11)-associated paraneoplastic neurological syndrome (PNS). METHODS Serial brain magnetic resonance images were retrospectively assessed. To test for KLHL11 autoantibodies, longitudinal cerebrospinal fluid (CSF) and serum samples were screened by Phage-display ImmunoPrecipitation and Sequencing (PhIP-Seq). Immunohistochemistry was also performed to assess for the presence of KLHL11 in the patient's seminoma tissue. RESULTS A 42-year-old man presented with progressive ataxia and sensorineural hearing loss. Metastatic seminoma was detected 11 months after the onset of the neurological symptoms. Although immunotherapy was partially effective, his cerebellar ataxia gradually worsened over the next 8 years. Brain magnetic resonance imaging revealed progressive brainstem and cerebellar atrophy with a "hot-cross-bun sign", and low-signal intensity on susceptibility-weighted imaging (SWI) in the substantia nigra, red nucleus and dentate nuclei. PhIP-Seq enriched for KLHL11-derived peptides in all samples. Immunohistochemical staining of mouse brain with the patient CSF showed co-localization with a KLHL11 commercial antibody in the medulla and dentate nucleus. Immunohistochemical analysis of seminoma tissue showed anti-KLHL11 antibody-positive particles in cytoplasm. CONCLUSIONS This study suggests that KLHL11-PNS should be included in the differential diagnosis for patients with brainstem and cerebellar atrophy and signal changes not only on T2-FLAIR but also on SWI, which might otherwise be interpreted as secondary to a neurodegenerative disease such as multiple system atrophy.

Background Pelvic fixation improves the stability of spinal instrumentation and can be used in high-grade degenerative disease, trauma, deformity, and destabilizing invasive pathologies, such as infection and tumor. Classic techniques for spinopelvic fixation include traditional iliac screws and S2-Alar-Iliac screws. We present a case series describing the distal ventral iliac pathway (DVIP) for spinopelvic fixation and discuss surgical indications and merits of this technique. We describe the use of the DVIP for spinopelvic fixation in the setting of degenerative and traumatic pathologies, compare this technique with existing approaches, and summarize literature to support this approach. Methods One hundred twenty-eight cases of DVIP screws were identified at 1 academic medical center, and 3 cases were chosen as representative examples for technique demonstration. Results Patient ages ranged from 19 to 81 (mean 62) years. Intraoperative and postoperative complications include 12 incidental durotomies, 3 suprafascial infections, and 2 compressive hematomas. There were 22 instances of hardware failure and 8 instances of pseudoarthrosis. Overall, 26 patients underwent revision surgery. Mean estimated blood loss, operative time, and time under fluoroscopy were 1959 mL, 386 minutes, and 3.19 minutes, respectively. Conclusions The DVIP is both safe and effective as a treatment for patients with degenerative and traumatic lumbosacral pathology. Spinopelvic fixation provides improved soft tissue coverage and fewer hardware complications at minimum of 1 year follow up. This case series demonstrates a novel surgical technique for spinopelvic fixation in the setting of numerous spinal pathologies. Level of Evidence 4. Clinical Relevance This surgical technique is less technically challenging than current approaches, minimizes radiation exposure, and obviates the need for horizontal connector rods. In addition, in highly destabilizing pathologies, this technique also allows for multiple screw placement within the ilium, while maintaining the ability to connect to a single rod construct. This technique is safe, technically approachable, and broadly applicable to an array of spinopelvic pathologies.

BACKGROUND Suction and capillary pull are 2 biopsy techniques used in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Although these techniques have been shown to perform comparably in terms of overall diagnostic yield, we hypothesized that the capillary pull technique would be associated with improved rapid on-site evaluation (ROSE) adequacy rates thus allowing for a shorter procedure time. METHODS One hundred eighteen patients undergoing EBUS-TBNA for any indication were randomized to suction or capillary pull techniques for the first biopsy pass; the technique used for all subsequent passes was based on operator preference and was not recorded. The first pass was subjected to ROSE and an adequacy assessment was given. ROSE slides were also scored for cellularity of diagnostic/lesional cells and blood contamination. The overall procedure time was also recorded. RESULTS There were no significant differences between suction and capillary pull techniques in terms of ROSE adequacy rates. Cellularity of diagnostic/lesional cells and blood contamination scores were also comparable. There was no significant difference in procedure time for the 2 techniques. CONCLUSION This study suggests no differences in ROSE outcomes between suction and capillary pull techniques in EBUS-TBNA. The technique used should therefore be left to the discretion of the operator.

Objectives To describe the methodology and implications of the patient‐identified most bothersome symptom (PI‐MBS) measure used in the phase 3, multicenter, randomized, double‐blind, placebo‐controlled, and parallel‐group PROMISE‐2 trial and to evaluate the contribution of this measure to the assessment of the preventive migraine benefits of treatment. Background Although freedom from MBS is a coprimary endpoint in acute migraine treatment trials, its evaluation in preventive migraine trials is limited. The PROMISE‐2 study assessed a unique PI‐MBS measure as a secondary endpoint. Methods This was a secondary analysis of data from the PROMISE‐2 study. Adults with chronic migraine (CM) were randomized to receive intravenous (IV) eptinezumab 100 mg, eptinezumab 300 mg, or placebo, administered on day 0 and every 12 weeks. At the screening visit, patients were asked to verbally describe the MBS associated with their CM; the question format was open ended. At subsequent visits, patients were asked to rate the overall change in severity of their MBS from study inception to that time point, using a 7‐point ordinal scale ranging from “very much worse” (−3) to “very much improved” (+3). Patients completed the Patient Global Impression of Change (PGIC) assessment during the same visits, using an identical rating scale and recall period. Endpoints were summarized descriptively; post hoc correlations using the methodologies of Pearson and Spearman were calculated to evaluate relationships between PGIC and PI‐MBS and between PGIC and mean monthly migraine days (MMDs; primary efficacy endpoint in PROMISE‐2). Results Altogether, 1072 patients received treatment (eptinezumab 100 mg, n = 356; eptinezumab 300 mg, n = 350; placebo, n = 366) and were included in the analysis. There were 23 unique MBS identified; those reported by ≥10 patients included light sensitivity (18.7%), nausea/vomiting (15.1%), pain with activity (13.7%), pain (12.4%), headache (11.2%), sound sensitivity (7.3%), throbbing/pulsating pain (4.7%), cognitive disruption (4.1%), fatigue (2.4%), mood changes (1.5%), and sensitivity to smell (0.9%). Four weeks after the first dose (week 4), the rates of much or very much improvement in PI‐MBS were higher with eptinezumab 100 mg (45%) and 300 mg (57%) than with placebo (29%). Four weeks after the second dose (week 16), the proportions with much or very much improvement in PI‐MBS had increased to 58%, 65%, and 36%, respectively. At each time point, the percentages of patients with PGIC ratings of much or very much improved were similar to those for patient‐reported improvement in PI‐MBS. Patient ratings of changes in PI‐MBS and PGIC correlated strongly across time points (Pearson, r range, 0.83–0.88; Spearman, r range, 0.83–0.89); the absolute value of the correlations was greater than the correlation among changes in MMDs and PGIC (Pearson, r range, −0.49 to −0.52; Spearman, r range, −0.49 to −0.52). Conclusions Among patients with CM in the PROMISE‐2 study, a broad range of PI‐MBS was reported at baseline. Throughout the study, patients treated with eptinezumab reported greater improvement in their PI‐MBS severity compared with placebo recipients, and this improvement correlated strongly with PGIC findings. Collectively, these results indicate that PI‐MBS is a promising and novel outcome measure for preventive trials of CM and thus may provide a unique patient‐centered approach for identifying and measuring the burden of migraine symptoms that matter most to each patient, as well as the benefits of treatment.

Objective:On March 11, 2020, the World Health Organization declared an outbreak of a new viral entity, coronavirus 2019 (COVID-19), to be a worldwide pandemic. The characteristics of this virus, as well as its short- and long-term implications, are not yet well understood. The objective of the current paper was to provide a critical review of the emerging literature on COVID-19 and its implications for neurological, neuropsychiatric, and cognitive functioning.Method:A critical review of recently published empirical research, case studies, and reviews pertaining to central nervous system (CNS) complications of COVID-19 was conducted by searching PubMed, PubMed Central, Google Scholar, and bioRxiv.Results:After considering the available literature, areas thought to be most pertinent to clinical and research neuropsychologists, including CNS manifestations, neurologic symptoms/syndromes, neuroimaging, and potential long-term implications of COVID-19 infection, were reviewed.Conclusion:Once thought to be merely a respiratory virus, the scientific and medical communities have realized COVID-19 to have broader effects on renal, vascular, and neurological body systems. The question of cognitive deficits is not yet well studied, but neuropsychologists will undoubtedly play an important role in the years to come.

Lyme disease, which is primarily caused by infection with the bacterium Borrelia burgdorferi in the United States or other Borrelia species internationally, presents an ongoing challenge for diagnostics. Serological testing is the primary means of diagnosis but testing approaches differ widely, with varying degrees of sensitivity and specificity. Moreover, there is currently no reliable test to determine disease resolution following treatment. A distinct challenge in Lyme disease diagnostics is the variable patterns of human immune response to a plurality of antigens presented by Borrelia spp. during the infection. Thus, multiplexed testing approaches that capture these patterns and detect serological response against multiple antigens may be the key to prompt, accurate Lyme disease diagnosis. In this review, current state-of-the-art multiplexed diagnostic approaches are presented and compared with respect to their diagnostic accuracy and their potential for monitoring response to treatment.

The 2019 novel coronavirus disease (COVID-19) pandemic produced an abrupt and near shutdown of nonemergent patient care. Children's National Hospital (CNH) mounted a multidisciplinary, coordinated ambulatory response that included supply chain management, human resources, risk management, infection control, and information technology. To ensure patient access, CNH expanded telemedicine and instituted operational innovations for outpatient procedures. While monthly in-person ambulatory subspecialty visits decreased from 25 889 pre-COVID-19 to 4484 at nadir of the COVID-19 pandemic, telemedicine visits increased from 70 to 13 539. Further studies are needed to assess the impact of innovations in health care delivery and operations that the crisis prompted.

The Family Check-Up 4 Health (FCU4Health) is an adaptation of the Family Check-Up (FCU) for delivery in primary care settings. While maintaining the original FCU’s focus on parenting and child behavioral health, we added content targeting health behaviors. This study evaluated whether the adapted FCU maintained positive effects on parenting (positive behavior support, limit setting, parental warmth) and child behavioral health (self-regulation, conduct problems, emotional problems). Pediatric (6–12 years) primary care patients with a BMI ≥ 85th%ile (n = 240) were recruited from primary care clinics in Phoenix. Children were 75% Latino, 49% female, and 73% Medicaid recipients. This type 2 effectiveness-implementation hybrid trial compared families randomized to FCU4Health (n = 141) or usual care (n = 99). FCU4Health was delivered over a period of 6 months. This study focuses on a priori secondary outcomes included parenting and child behavioral health targets of the original FCU, assessed at baseline and 3, 6, and 12 months. Significant improvements were found for the FCU4Health condition, compared to usual care, in parenting from baseline to the 3-month assessment [β = .17 (.01; .32)]. Parenting predicted improvements in child self-regulation at 6-months [β = .17 (.03; .30)], which in turn predicted reductions in conduct problems [β = − .38 (− .51; − .23)] and emotional problems [β = − .24 (− .38; − .09)] at 12 months. Ethnicity and language of delivery (English or Spanish) did not moderate these effects. The FCU4Health can improve parenting and child behavioral health outcomes when delivered in primary care. Trial Registration Trial registration number: NCT03013309 ClinicalTrials.gov

Background Eptinezumab, an anti-calcitonin gene-related peptide monoclonal antibody recently approved in the United States for preventive treatment of migraine in adults, was found to be well tolerated in double-blind, placebo-controlled studies in patients with episodic and chronic migraine. The objective of the PREVAIL study was to evaluate the long-term safety, immunogenicity, and impact on patient-reported outcomes of repeat doses of eptinezumab in patients with chronic migraine. Methods PREVAIL was an open-label, phase 3 trial comprising a 48-week treatment phase followed by a second 48-week treatment phase. Adults with chronic migraine received eptinezumab 300 mg by 30-min intravenous administration every 12 weeks for up to 8 doses. Patients were followed for 20 weeks after the final infusion (end-of-study visit at week 104). Results Overall, 128 adults (mean age, 41.5 years) with chronic migraine were included. During the 2 years, the most frequently reported treatment-emergent adverse events were nasopharyngitis (14.1%), upper respiratory tract infection (7.8%), sinusitis (7.8%), influenza (6.3%), bronchitis (5.5%), and migraine (5.5%). The rate of study-drug discontinuation due to adverse events was 6.3%, which included 3 patients with infusion-related hypersensitivity. The incidence of anti-eptinezumab antibodies peaked at week 24 and declined despite continued dosing, to nondetectable levels at week 104. Improvements in patient-reported outcomes were observed at first assessment (week 4) and generally sustained through week 104. Conclusion In adults with chronic migraine, eptinezumab 300 mg demonstrated a favorable safety profile, limited long-term immunogenicity, early and sustained reductions in migraine-related burden, and improvements in health-related quality of life over 2 years. Trial registration ClinicalTrials.gov (Identifier: NCT02985398).

Proximal hamstring tendon avulsions are a relatively rare type of hamstring injury associated with persistent morbidity, including pain, weakness, and functional limitations. Open or endoscopic surgical repair is the standard treatment for complete tendon avulsions or partial tears that remain symptomatic despite conservative management in relatively young, healthy, and active patients. However, complications known to occur include retearing of the hamstring, infection, nerve injury, inability to return to work or sport, subjective persistent weakness, and subjective persistent pain. In the case of persistent pain where the repair is partially retorn, a careful history, physical examination, and scrutiny of radiologic studies can help guide management. We describe a technique for using revision endoscopy and augmentation with a bovine bioinductive patch in a case of chronic persistently painful partial retear after a proximal hamstring repair., Technique Video Video 1 This video demonstrates a technique for endoscopic implantation of a bioinductive patch for symptomatic chronic partial retearing of the proximal hamstring after failed repair. This is a case of chronic partial retearing of the right proximal hamstring, 2 years out from the index repair. T2 coronal imaging shows signal within the repair and the axial view shows a prominent suture anchor laterally with retearing of the semimembranosus. The patient was indicated for revision endoscopy after not responding to nonoperative management. The patient was placed in the prone position after general anesthesia. The right lower extremity was prepped and draped in the usual sterile fashion. The previous direct posterior portal in the gluteal crease was used to introduce a 30° arthroscope into the space between the gluteus maximus and ischial tuberosity. Next, a superolateral working portal was established to perform an ischial bursectomy. The sciatic nerve was then identified and a thorough neurolysis was performed. The proximal hamstring repair site was debrided and visualized revealing a prominent suture anchor and partial retear superolaterally. The suture anchor was burred down using a 5.5 partially hooded round burr. The arthroscope was then switched to the superolateral portal, and a third portal was made approximately 3-4 fingerbreadths proximal to the direct posterior portal to help facilitate staple fixation of the implant. A medium bioinductive patch is then passed through the direct posterior portal with the assistance of a skid and centered over the proximal hamstring tendon origin. Staple fixation was performed until sufficiently stable to remove the inserter. Additional fixation was then performed until adequate stability was achieved.

Decades of research have shown that biosensors using photonic circuits fabricated using CMOS processes can be highly sensitive, selective, and quantitative. Unfortunately, the cost of these sensors combined with the complexity of sample handling systems has limited the use of such sensors in clinical diagnostics. We present a new "disposable photonics" sensor platform in which rice-sized (1 × 4 mm) silicon nitride ring resonator sensor chips are paired with plastic micropillar fluidic cards for sample handling and optical detection. We demonstrate the utility of the platform in the context of detecting human antibodies to SARS-CoV-2, both in convalescent COVID-19 patients and for subjects undergoing vaccination. Given its ability to provide quantitative data on human samples in a simple, low-cost single-use format, we anticipate that this platform will find broad utility in clinical diagnostics for a broad range of assays.

Despite drawing inspiration from biological systems which are inherently noisy and variable, artificial neural networks have been shown to require precise weights to carry out the task which they are trained to accomplish. This creates a challenge when adapting these artificial networks to specialized execution platforms which may encode weights in a manner which restricts their accuracy and/or precision. Reflecting back on the non-idealities which are observed in biological systems, we investigated the effect these properties have on the robustness of spiking neural networks under perturbations to weights. First, we examined techniques extant in conventional neural networks which resemble noisy processes, and postulated they may produce similar beneficial effects in spiking neural networks. Second, we evolved a set of spiking neural networks utilizing biological non-idealities to solve a pole-balancing task, and estimated their robustness. We showed it is higher in networks using noisy neurons, and demonstrated that one of these networks can perform well under the variance expected when a hafnium-oxide based resistive memory is used to encode synaptic weights. Lastly, we trained a series of networks using a surrogate gradient method on the MNIST classification task. We confirmed that these networks demonstrate similar trends in robustness to the evolved networks. We discuss these results and argue that they display empirical evidence supporting the role of noise as a regularizer which can increase network robustness.

Societal Impact Statement Forest products are the most used inedible renewable resource, but supplies are finite. It is difficult to know which tree species are in wood products or where they come from. Scientific evidence is needed to support or refute origin and species claims in traded products. We describe the building of a geo‐referenced wood reference collection (xylarium) supported by herbarium voucher specimens. The WorldForest ID program, hereinafter referred to as WFID (www.worldforestid.org), is embarking on large‐scale field collections of wood samples suitable for science‐based authentication technologies. By coordinating with regulatory and enforcement authorities in both producer and consumer countries the WFID xylarium is legally robust and commercially relevant. Summary We describe a program called WorldForestID which is being developed to monitor and support authentication and compliance in international trade of timber products. The program is being run by a consortium of government and non‐government organizations: US Forest Service International Programs (USFS IP), Royal Botanic Gardens, Kew, Forest Stewardship Council (FSC), Agroisolab, and World Resources Institute (WRI). Initial funding has come from the US Department of State, USFS IP, US Department of Agriculture Animal and Plant Health Inspection Service, Forest Stewardship Council, and the UK Department for Environment, Food and Rural Affairs (Defra). The aim is to build a comprehensive collection of internationally traded timber species. The collection is used as reference material to validate forest products. Although there are a large number of xylaria (wood collections, Index Xylariorum IV) around the world, many of the specimens do not provide geo‐locations suitable as reference material for pinpointing provenance, many lack‐associated herbarium vouchers and some are misidentified. The samples being collected in this program address these issues and include bark, sapwood, and heartwood, ensuring that the material collected is suitable for current and future scientific analysis. We describe the process of collection and validation from field to laboratory and the advantages and disadvantages of the main techniques used to ascertain/verify identity and provenance. Ultimately, we envisage the day that scientific methods will be used routinely and successfully by timber traders, manufacturers, retailers, and law enforcement to accept or reject identity and provenance claims on internationally traded timber and forest products and, where necessary, to support prosecutions when laws such as EU Timber Regulations, Lacey Act and CITES are infringed.

Objective To compare Patient-Reported Outcomes Measurement Information System (PROMIS) measures of depression and anxiety to the Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), and explore patterns of selected PROMIS measures in patients undergoing evaluation for Deep Brain Stimulation (DBS). Method BDI-II, BAI, and seven PROMIS measures were administered to 163 DBS candidates with diagnoses of Parkinson Disease (PD, n = 102), Essential Tremor (ET, n = 45), or Dystonia (n = 16). Results Elevated PROMIS Depression using BDI-II Crosswalk equivalents predicted elevated BDI-II with 63% sensitivity and 94% specificity. On other PROMIS measures, 69 patients (42%) reported low Physical Function (T ≤ 40) with Pain Interference being the next most frequent abnormal score (n = 51, 31%). Group differences were present for PROMIS Physical Function, Sleep Disturbance, and Pain. Conclusions These preliminary findings provide initial support for PROMIS Depression to assess mood disturbance in DBS candidates, and characterize other PROMIS measures in DBS candidates including group differences reflecting disease specific contribution to Quality of Life.

Objective To determine the onset of preventive efficacy with eptinezumab in patients with migraine. Background Eptinezumab is a monoclonal antibody inhibiting calcitonin gene‐related peptide approved as an intravenously administered treatment for the prevention of migraine. Methods Patients who received eptinezumab 100 mg, eptinezumab 300 mg, or placebo in PROMISE7‐1 (episodic migraine; 100 mg, n = 221; 300 mg, n = 222; placebo, n = 222) or PROMISE7‐2 (chronic migraine; 100 mg, n = 356; 300 mg, n = 350; placebo, n = 366) were included. Testing of the percentage of patients with a migraine on day 1 after dosing was prespecified and alpha‐controlled. In further exploration of this prespecified endpoint, a post hoc closed testing procedure, which controlled the false‐positive (type 1) error rate, provided a statistically rigorous evaluation of migraine prevention onset. The procedure involved up to 84 tests of significance, all of which were performed in sequence until the first nonsignificant result. Results For both studies, all tests for significance for eptinezumab 100 and 300 mg, from days 1‐84 through day 1 alone, achieved nominal significance (P

Background PROMISE-2 was a phase 3, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of repeat intravenous (IV) doses of the calcitonin gene-related peptide–targeted monoclonal antibody eptinezumab (ALD403) for migraine prevention in adults with chronic migraine. This report describes the results of PROMISE-2 through 24 weeks of treatment. Methods Patients received up to two 30-min IV administrations of eptinezumab 100 mg, 300 mg, or placebo separated by 12 weeks. Patients recorded migraine and headache endpoints in a daily eDiary. Additional assessments, including patient-reported outcomes, were performed at regularly scheduled clinic visits throughout the 32-week study period (screening, day 0, and weeks 2, 4, 8, 12, 16, 20, 24, and 32). Results A total of 1072 adults received treatment: eptinezumab 100 mg, n = 356; eptinezumab 300 mg, n = 350; placebo, n = 366. The reduction in mean monthly migraine days observed during the first dosing interval (100 mg, − 7.7 days; 300 mg, − 8.2 days; placebo, − 5.6 days) was further decreased after an additional dose (100 mg, − 8.2 days; 300 mg, − 8.8 days; placebo, − 6.2 days), with both doses of eptinezumab demonstrating consistently greater reductions from baseline compared to placebo. The ≥50% and ≥ 75% migraine responder rates (MRRs) increased after a second dose, with more eptinezumab-treated patients experiencing migraine response than placebo patients (≥50% MRRs weeks 13–24: 100 mg, 61.0%; 300 mg, 64.0%; placebo, 44.0%; and ≥ 75% MRRs weeks 13–24: 100 mg, 39.3%; 300 mg, 43.1%; placebo, 23.8%). The percentages of patients who improved on patient-reported outcomes, including the Headache Impact Test and Patient Global Impression of Change, increased following the second dose administration at week 12, and were greater with eptinezumab than with placebo at all time points. No new safety concerns were identified with the second dose regarding the incidence, nature, and severity of treatment-emergent adverse events. Conclusion Eptinezumab 100 mg or 300 mg administered IV at day 0 and repeated at week 12 provided sustained migraine preventive benefit over a full 24 weeks and demonstrated an acceptable safety profile in patients with chronic migraine. Trial registration ClinicalTrials.gov (Identifier: NCT02974153). Registered November 23, 2016.

OBJECTIVE This study aimed to evaluate the use of levofloxacin for the prevention of bacterial infections in pediatric patients with acute myeloid leukemia or those undergoing hematopoietic stem cell transplantation. METHODS This study was a single-center, retrospective review designed to assess the frequency of bacteremia with levofloxacin prophylaxis compared with historical controls that used other, clinician-directed antibacterial prophylaxis. The primary outcome of the study was microbiologically documented bacteremia. Secondary outcomes included febrile neutropenia, clinically documented infection, duration of neutropenia, treatment antibiotic exposure days, Clostridioides difficile infection, and infection-related mortality. RESULTS Of the 60 patients included, 24 patients with 32 hospital admissions received levofloxacin and 36 patients with 48 hospital admissions received clinician-directed prophylaxis. There was no difference found in the frequency of bacteremia between levofloxacin and clinician-directed prophylaxis (15.6% vs 10.4%, p = 0.49). There was no difference in the incidence of febrile neutropenia, clinically documented infection, treatment antibiotic exposure days, or 30-day infection-related mortality between the 2 groups. The levofloxacin group had a longer mean duration of neutropenia compared with clinician-directed prophylaxis (26.8 days vs 16.4 days, p = 0.01). CONCLUSIONS There was no difference in bacteremia between levofloxacin prophylaxis and clinician-directed prophylaxis in pediatric patients with acute myeloid leukemia or those undergoing hematopoietic stem cell transplantation. Levofloxacin prophylaxis is an appropriate alternative for the prevention of serious bacterial infections in this patient population, although further studies are needed to confirm these results.

NPs piloted a family-centered goal-planning tool with a medically complex pediatric population during outpatient clinic visits. The tool was an effective reminder to discuss goals after trust and rapport are established between provider and family.

Objective To evaluate the efficacy and safety of eptinezumab, a humanized anti-calcitonin gene-related peptide monoclonal antibody, in the preventive treatment of episodic migraine. Methods The PRevention Of Migraine via Intravenous ALD403 Safety and Efficacy-1 (PROMISE-1) study was a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Adults with episodic migraine were randomized to eptinezumab 30 mg, 100 mg, 300 mg, or placebo for up to four intravenous (IV) doses administered every 12 weeks. The primary endpoint was change from baseline in monthly migraine days (MMDs) over weeks 1–12. Results A total of 888 patients received treatment across 84 study sites. Mean MMDs at baseline was ∼8.6 across treatment groups. Eptinezumab 100 mg and 300 mg met the primary endpoint, significantly reducing MMDs across weeks 1–12 compared with placebo (30 mg, −4.0; 100 mg, −3.9, p = 0.0182; 300 mg, −4.3; placebo, −3.2, p = 0.0001). Treatment-emergent adverse events were reported by 58.4% (30 mg), 63.2% (100 mg), 57.6% (300 mg), and 59.5% (placebo) of patients. Treatment-emergent adverse events reported by ≥2% of eptinezumab-treated patients at an incidence greater than placebo included: upper respiratory tract infection (30 mg, 11.4%; 100 mg, 9.9%; 300 mg, 10.3%; placebo, 7.2%), and fatigue (30 mg, 2.3%; 100 mg, 3.6%; 300 mg, 3.6%; placebo, Conclusion Eptinezumab (100 mg or 300 mg) significantly reduced migraine frequency, was well tolerated, and had an acceptable safety profile when used for the preventive treatment of migraine in adults with episodic migraine. ClinicalTrials.gov identifier: NCT02559895

Objective:Cerebrotendinous xanthomatosis (CTX) belongs to a heterogeneous group of neurological disorders known as autosomal recessive cerebellar ataxias. Low awareness of CTX can result in misdiagnoses in the differential diagnostic process and may limit one’s ability to offer suitable recommendations. While neurodegeneration is a recognized manifestation of CTX, there is scant literature to characterize the nature of cortical symptoms and even less detailing of its associated neurocognitive and neuropsychiatric manifestations.Method:Based on the lack of representation of CTX in neuropsychological literature, we sought to present a case seen in a 39-year-old patient within our own clinic.Results:Evaluation of the patient’s neurocognitive functioning revealed global impairment consistent with a CTX diagnosis and neuroimaging findings noting significant cerebellar involvement.Conclusions:Neuropsychologists are increasingly called upon to make treatment recommendations and provide information that may be helpful in differential diagnosis as part of multidisciplinary teams. Referrals from neurology are common, and it is important for neuropsychologists to be aware of diseases that affect the central nervous system; CTX is one such example. The goal of this case study is to build awareness of this condition and increase interest in a more systematic approach to research and clinical care of this population.

Ammonia (NH3) plays an important role in atmospheric chemistry and is one of the key components for aerosol (particulate matter—PM2.5) formation, which can have deleterious effects on the environment and population health locally and regionally. This chapter describes the spatiotemporal variations in atmospheric NH3 concentrations using satellite observations over South Asia. The NH3 hot spots are mainly associated with the major agricultural regions of South Asia. The highest NH3 concentrations are observed over the densely populated Indo-Gangetic Plains (IGP) region, which is the main agricultural region of South Asia. The interannual and seasonal variability in NH3 concentrations are strongly influenced by the changes in meteorology and agricultural practices in the regions. The main agricultural regions of South Asia show a general increase in NH3 concentrations in the study period from 2013 to 2018.

Background Patients with migraine have an increased relative risk of cardio- and cerebrovascular events, and some migraine treatments may exacerbate this risk. The primary objective of this analysis was to determine whether the rate of cardiovascular adverse events was higher for patients with migraine treated with the migraine-preventive eptinezumab, compared with patients receiving placebo. Methods Cardiovascular outcomes in patients with migraine were pooled across four clinical trials (phase 1b, phase 2, and two phase 3 trials) for use of eptinezumab as a preventive migraine treatment for up to 1 year. In all studies, treatment-emergent adverse events (TEAEs) that occurred after the first dose of study treatment (eptinezumab 100 mg, 300 mg, 1000 mg, or placebo) and vital signs were recorded through study completion. Results Cardiovascular TEAEs were rare across all four clinical trials, and rates were similar between patients receiving eptinezumab and those receiving placebo. Cardiovascular TEAEs that did occur were mild or moderate in severity; there were no serious adverse events as per FDA definition. Vital signs (systolic blood pressure, diastolic blood pressure, and heart rate) were not meaningfully different across treatment groups over the course of 56 weeks, compared to placebo. Treatment with eptinezumab did not result in significant new or changed cardiovascular medications used concomitantly compared to placebo. Conclusions In this post hoc analysis of four clinical trials for eptinezumab, doses of 100 mg, 300 mg, and 1000 mg (more than 3 times the highest approved dose) were not associated with clinically relevant changes in vital signs or significant changes in concomitant cardiovascular medication usage, and had low incidences of cardiovascular TEAEs, comparable to placebo. Trial registration NCT01772524 (Study 2), 01/21/2013; NCT02275117 (Study 5), 10/27/2014; NCT02559895 (PROMISE-1), 09/25/2017; NCT02974153 (PROMISE-2), 11/28/2016

Background Since the 1990s, the U.S. has faced increasing rates of opioid overuse, misuse, and overdose deaths. To combat the opioid epidemic, there have been national initiatives to limit prescribing of opioids. At our institution, we implemented an opioid-sparing protocol in pediatric surgical patients and sought to evaluate its impact on postoperative opioid prescribing patterns. Methods A retrospective chart review of the electronic medical record was performed for 9- to 18-year-old patients who underwent a laparoscopic appendectomy or cholecystectomy before and after the implementation of an opioid-sparing protocol. Data on postoperative opioids administered during the hospitalization and prescribed at discharge, postoperative pain control, use of non-opioid analgesics, and safety were collected. Results A total of 81 patient charts were analyzed. The median amount of opioids administered during hospitalization was 8 MMEs and 15 MMEs in the pre-implementation and post-implementation, respectively ( P = 0.310). The median amount of opioids prescribed at discharge was 150 MMEs and 60 MMEs in the pre-implementation and post-implementation, respectively ( P = 0.006). Patients reported mild pain scores throughout the hospitalization in both groups. Discussion Among young patients who underwent laparoscopic appendectomy or cholecystectomy, the administration of opioids during hospitalization for postoperative pain was minimal. The opioid sparing protocol did not reduce the amount of inpatient postoperative opioids administered but found a decrease in the amount of opioids prescribed at discharge. The study findings identified further areas of intervention and education to optimize postoperative opioid prescribing after these common pediatric surgical procedures.

NPs care for persons across the age continuum and transitions commonly occur. Some are unexpected, like hospitalizations for acute illness or injury. Others are an expected consequence of growing up, like moving from pediatric to adult care models. Understanding the factors impacting healthcare transition is critical for successful outcomes.

BackgroundEptinezumab is a humanized monoclonal antibody that selectively binds calcitonin gene-related peptide and is indicated for the preventive treatment of migraine in adults. This analysis characterizes the immunogenic profile of eptinezumab using data from clinical trials of eptinezumab for migraine prevention.MethodsImmunogenicity data were collected from five studies that included 2076 patients with episodic or chronic migraine treated with eptinezumab at dose levels ranging from 10 to 1000 mg, administered intravenously for up to 4 doses at 12-week intervals. Anti-drug antibody (ADA) results were available from 2074 of these patients. Four studies were randomized, double-blind, placebo-controlled trials with ADA monitoring for up to 56 weeks; one was a 2-year, open-label, phase 3 safety study with ADA monitoring for 104 weeks. Patients who had a confirmed ADA-positive result at the end-of-study visit were monitored for up to 6 additional months. Development of ADA and neutralizing antibodies (NAbs) were evaluated to explore three key areas of potential impact: pharmacokinetic exposure profile (eptinezumab trough plasma concentrations), efficacy (change in monthly migraine days), and safety (rates of treatment-emergent adverse events). These studies included methods designed to capture the dynamics of a potential humoral immune response to eptinezumab treatment, and descriptive analyses were applied to interpret the relationship of ADA signals to drug exposure, efficacy, and safety.ResultsPooled across the five clinical trials, treatment-emergent ADAs and NAbs occurred in 15.8 and 6.2% of eptinezumab-treated patients, respectively. Highly consistent profiles were observed across all studies, with initial onset of detectable ADA observed at the week 8 measurement and maximal ADA frequency and titer observed at week 24, regardless of eptinezumab dose level or number of doses. After 24 weeks, the ADA and NAb titers steadily declined despite additional doses of eptinezumab.InterpretationCollectively, these integrated analyses did not demonstrate any clinically meaningful impact from ADA occurring after treatment with eptinezumab. The ADA profiles were low titer and transient, with the incidence and magnitude of ADA or NAb responses declining after week 24. Development of ADAs and NAbs did not impact the efficacy and safety profiles of eptinezumab.

Agricultural emissions of ammonia (NH3) impact air quality, human health, and the vitality of aquatic and terrestrial ecosystems. In the UK, there are few direct policies regulating anthropogenic NH3 emissions and development of sustainable mitigation measures necessitates reliable emissions estimates. Here, we use observations of column densities of NH3 from two space-based sensors (IASI and CrIS) with the GEOS-Chem model to derive top-down NH3 emissions for the UK at fine spatial (similar to 10 km) and time (monthly) scales. We focus on March-September when there is adequate spectral signal to reliably retrieve NH3. We estimate total emissions of 272 Gg from IASI and 389 Gg from CrIS. Bottom-up emissions are 27% less than IASI and 49% less than CrIS. There are also differences in seasonality. Top-down and bottom-up emissions agree on a spring April peak due to fertilizer and manure application, but there is also a comparable summer July peak in the top-down emissions that is not in the bottom-up emissions and appears to be associated with dairy cattle farming. We estimate relative errors in the top-down emissions of 11%-36% for IASI and 9%-27% for CrIS, dominated by column density retrieval errors. The bottom-up versus top-down emissions discrepancies estimated in this work impact model predictions of the environmental damage caused by NH3 emissions and warrant further investigation.

Future planned space telescopes such as HabEx and LUVOIR will be used to directly image exo-Earths. These telescopes use coronagraph instruments to suppress starlight and resolve dim exoplanets. They will employ high order wavefront sensing and control (HOWFSC) to correct static and slow wavefront errors in the image plane to achieve contrasts above 109. This work evaluates architectures to meet the computational requirements for HOWFSC algorithms with available processors. We find that the computational requirements of HOWFSC will impose unprecedented requirements on space-based components and that typical combinations of computational resource and control architecture will consume significant observation time. Science yield from the space telescope can be improved, and mission risk and cost reduced, by using co-flying or ground-in-the loop computational offload architectures. In particular, a high-capability co-flying processor could use commercial components 104 times more powerful than typical radiation hardened options. This would enable key HOWFSC algorithms to run in seconds rather than hours or days, removing operational constraints on the science mission. While commercial processors may be more susceptible to total ionizing dose radiation effects over the expected mission lifetime of 5-10 years, the relatively low cost of development and replacement launches make these co-flying processors an attractive option. We evaluate three major co-flying architecture trades: (i) inter-spacecraft distance, (ii) risk classification, and (iii) processor selection. We find that one or more low-cost replaceable co-flying processors with COTS components and flying several kilometers from the telescope spacecraft can provide all needed computation.

Error-correcting codes (ECC) are widely used during data transfer in wireless communication systems as well as in computer memory architectures. The error-correcting process is based on sending data with extra parity bits and decoding the received data for error correction. The first error detection and correction code, introduced in 1950, Hamming Code (7,4) is a linear error-correcting code able to detect and correct a single-bit error by encoding 7-bit data from 4-bit data, including 3 parity bits. Previous efforts using unipolar resistive random access memory (ReRAM) based in-memory computation of Hamming Code (7,4) resulted in 102 times lower power consumption compared to GPU and 103 times less than CPU-based computations. However further reduction of power consumption can be achieved by vector-matrix multiplication (VMM) using bipolar ReRAM arrays. In the VMM based approach, an encoding or decoding code matrix is stored in the array where it leverages the nonvolatile properties of ReRAM. With the VMM approach, the total number of computation cycles is not limited by the endurance of the ReRAM devices. Here we report the first experimental results of encoding and decoding Hamming code (7,4) using 1 transistor 1 hafnium oxide-based ReRAM (1T1R) arrays fabricated using 65nm CMOS technology. Our results show bipolar 1T1R arrays can correctly encode 4-bit message data to 7 bit encoded data as well as error position detection with overall 3 fold less power consumption than previously reported unipolar ReRAM crossbar array-based computation. Furthermore, we propose and simulate a peripheral circuit to convert the analog column output from a 1T1R array to single-bit binary output using the Cadence Spectre simulator. Our results pave the way for using a memristor-based fast and scalable hardware solution for encoding decoding of error-correcting codes

Background Musculoskeletal conditions are highly prevalent, and knee OA is most common. Current treatment modalities have limitations and either fail to solve the underlying pathophysiology or are highly invasive. To address these limitations, attention has focused on the use of biologics. The efficacy of these devices is attributed to presence of growth factors (GFs), cytokines (CKs), and extracellular vesicles (EVs). With this in mind, we formulated a novel cell-free stem cell-derived extract (CCM) from human progenitor endothelial stem cells (hPESCs). A preliminary study demonstrated the presence of essential components of regenerative medicine, namely GFs, CKs, and EVs, including exosomes, in CCM. The proposed study aims to evaluate the safety and efficacy of intraarticular injection of the novel cell-free stem cell-derived extract (CCM) for the treatment of knee OA. Methods and analysis This is a non-randomized, open-label, multi-center, prospective study in which the safety and efficacy of intraarticular CCM in patients suffering from grade II/III knee OA will be evaluated. Up to 20 patients with grade II/III OA who meet the inclusion and exclusion criteria will be consented and screened to recruit 12 patients to receive treatment. The study will be conducted at up to 2 sites within the USA, and the 12 participants will be followed for 24 months. The study participants will be monitored for adverse reactions and assessed using Numeric Pain Rating Scale (NPRS), Patient-Reported Outcomes Measurement Information System (PROMIS) Score, Knee Injury and Osteoarthritis Outcome Score Jr. (KOOS Jr.), 36-ietm short form survey (SF-36), Single Assessment Numeric Evaluation (SANE), physical exams, plain radiography, and magnetic resonance imaging (MRI) with Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score for improvements in pain, function, satisfaction, and cartilage regeneration. Discussion This prospective study will provide valuable information into the safety and efficacy of intraarticular administration of cell-free stem cell-derived extract (CCM) in patients suffering with grade II/III knee OA. The outcomes from this initial study of novel CCM will lay the foundation for a larger randomized, placebo-controlled, multi-center clinical trial of intraarticular CCM for symptomatic knee OA. Trial registration Registered on July 21, 2021. ClinicalTrials.gov NCT04971798

The radiation response of TaO x -based resistive memory (RRAM) devices fabricated in academic (Set A) and industrial (Set B) settings was compared. Ionization damage from a 60Co gamma source did not cause any changes in device resistance for either device type, up to 45 Mrad(Si). Displacement damage from a heavy ion beam caused a decrease in resistance at $1 \times 10 ^{21}$ oxygen displacements per cm3 in Set B devices in the high-resistance state (HRS); meanwhile, Set A devices did not exhibit any decrease in resistance due to displacement damage. Both types of devices exhibited an increase in resistance around $3 \times 10 ^{22}$ oxygen displacements per cm3, possibly due to the damage at the oxide/metal interfaces. These extremely high levels of damage represent near-total atomic disruption, and if this level of damage was ever reached, other circuit elements would likely fail before the RRAM devices in this article. Overall, both sets of devices were much more resistant to radiation effects than the similar devices reported in the literature. Displacement damage effects were only observed in the Set A devices once the displacement-induced oxygen vacancies surpassed the intrinsic vacancy concentration in the devices, suggesting that high oxygen vacancy concentration played a role in the devices’ high tolerance to displacement damage.

Background The short-form Headache Impact Test (HIT-6) is a widely used patient-reported outcome measure that assesses the negative effects of headaches on normal activity. It was developed using the general headache population and prior to the establishment of the now well-accepted FDA patient-reported guidance. Objective The objective of this narrative review was to examine existing qualitative research in patients with migraine and headache, providing insight into the relevance and meaningfulness of HIT-6 items to the lives of migraine patients. Methods Articles were identified through database searches (National Library of Medicine and Google Scholar) and review of reference lists of candidate articles. Results A total of 3227 articles were identified through database and hand searching. Of these, 12 contained patient- or expert-generated qualitative information regarding headache patients' experience (8 specific to migraine [episodic and chronic] patients and 4 citing general headache patients). The combined publications described a total of 283 patient interviews. Overarching themes and specific information were identified that provide support of the relevance of content for each HIT-6 item to migraine patients' lives. Identified effects of headaches on patients with migraine included limitations in daily activities, needing to lie down during headaches, feeling tired, being irritated by headaches, difficulty concentrating, and the experience of pain. Further, previous research specific to the HIT-6 indicated that patients understood the instructions, items, and response scales as intended by the instrument authors. Conclusions This narrative literature review demonstrates qualitative research support for the relevance of the items of the HIT-6 in migraine patients, supporting its ongoing use in clinical migraine research and practice.

Background Dispatcher CPR instruction increases the odds of survival. However, many communities do not provide this lifesaving intervention, often citing the barriers of limited personnel, funding, and liability. Objective Describe the implementation of a novel centralized dispatcher CPR instruction program that serves seven public safety answering points (PSAPs). Methods Seven municipal PSAPs that did not previously provide dispatcher instructions implemented our program. Using a 30-min self-directed video, 84 PSAP dispatchers were trained to utilize a two-question protocol to identify and transfer suspected out-of-hospital cardiac arrest (OHCA) cases to a central communication center. At this central communication center, a trained communicator delivered CPR instructions to the caller. The 26 central communicators were trained with a 2-h in-person didactic session followed by a 2-h practice session. We collected and analyzed data from recordings of communicator-to-caller interactions. Results 169 calls were transferred to the central communication center. Of those, 106 needed CPR instructions and 56 of those callers performed chest compressions (53%). The county-wide EMS documented bystander CPR rate was 20% the prior year. The 63 remaining transferred calls were non-OHCA calls. Of the calls where CPR was needed and performed, 11 victims survived to hospital discharge (20%); the countywide survival rate was 12%. Conclusions Using a central communication center for instructions allowed us to train and maintain a smaller group of communicators, leading to less cost and more experience for those communicators, while limiting the burden on PSAP dispatchers.

Background Early childhood is a critical period of development. Caregivers, including providers of early care and education (ECE), have a substantial influence on the health of young children. Family child care homes (FCCHs), which are small, licensed ECE businesses operated out of the residences of providers, are important settings for promoting child health. However, to date, few interventions to promote the health of children have been developed for FCCHs. The purpose of this article is to describe the protocol for Happy Healthy Homes, a pilot interdisciplinary, community-based study to improve FCCH environments and the health of children in Oklahoma. We describe the development and evaluation of two interventions to be tested in a matched attention randomized controlled trial: 1) a nutrition intervention aimed at enhancing the nutritional quality of meals served to young children, incorporating the Child and Adult Care Food Program best practices, and improving nutritional self-efficacy of providers; and 2) an environmental intervention aimed at increasing providers’ environmental health literacy, self-efficacy for integrated pest management (IPM), and awareness of less toxic cleaning practices and FCCH provider cleaning behaviors. Methods Both interventions are informed by common theoretical principles and are matched in attention (i.e., 6 h), format (i.e., two individual 90-min educational home visits and a 3-h small group class) and materials (i.e., tool kit of educational materials and supplies tailored to the allocated intervention). A randomized trial of both interventions is currently underway with 52 FCCH providers in the Oklahoma City metropolitan area who participate in the Child and Adult Care Food Program. Observed and self-reported measures will be collected at baseline, and 3 months and 12 months after baseline measurements. Randomization to one of the two interventions will occur after baseline data collection. Discussion This study aims to support FCCH providers in creating healthier FCCH environments for nutrition and environmental health. Successful completion will provide critical information about the nutritional quality and the environmental health of children in FCCHs, as well as much needed evidence about the efficacy of two community-based interventions to improve the nutrition and environmental health of children in home-based ECE settings. Trial registration Clinicaltrials.gov, NCT03560050. Retrospectively registered on 23 May 2018. Electronic supplementary material The online version of this article (10.1186/s13063-019-3616-9) contains supplementary material, which is available to authorized users.

Background Calcitonin gene-related peptide plays an important role in migraine pathophysiology. We evaluated eptinezumab, an intravenous (IV) anti-calcitonin gene-related peptide monoclonal antibody, for the prevention of chronic migraine. Objective To determine the safety, tolerability, and effectiveness of four dose levels of eptinezumab and to inform the phase 3 development program. Methods This was a phase 2b, parallel-group, double-blind, randomized, placebo-controlled, dose-ranging clinical trial. Men and women (N = 616) aged 18–55 years were included if they had a diagnosis of chronic migraine, with onset at age ≤35 years and history of chronic migraine ≥1 year. During the 28-day screening period, patients must have had ≥15 headache days, including ≥8 migraine days, with ≥5 migraine attacks as recorded in the electronic diary. Patients were assigned in a 1:1:1:1:1 ratio to eptinezumab 300, 100, 30, 10 mg or placebo, administered as a single IV infusion. The primary endpoint was the percentage of patients with a ≥75% decrease in monthly migraine days over weeks 1–12 compared with the 28-day screening period. Results The ≥75% migraine responder rates over weeks 1–12 for eptinezumab 300, 100, 30, and 10 mg were 33.3%, 31.4%, 28.2%, and 26.8%, respectively, versus 20.7% for placebo ( p = 0.033, 0.072, 0.201, 0.294 vs. placebo). Secondary efficacy endpoints (e.g. ≥50% responder rate, change from baseline in frequency of migraine/headache days, and percentage of severe migraines) had results favoring the three higher eptinezumab doses versus placebo. Eptinezumab was well tolerated and adverse event rates were similar to placebo. Conclusions The results of this trial demonstrate that eptinezumab appears effective and well-tolerated for the preventive treatment of chronic migraine and justifies the conduct of pivotal phase 3 trials for migraine prevention. Trial Registration ClinicalTrials.gov identifier: NCT02275117.

Purpose The purpose of this paper is to describe the process of fostering a maker culture in a liberal arts university. It explores the impact of making on student learning and engagement, as well as the role of the library’s maker program. Design/methodology/approach This paper is a case study that presents the tools and activities used in an academic library’s maker program. Structured interviews were conducted with faculty, staff and students to review the program and maker culture influence on campus. Findings Findings highlight the library’s role in supporting maker culture on a liberal arts campus and address ways making contributes to student engagement and learning. Interviewees also recommend strategies to increase awareness and market the library’s maker program to engage a wider community. Originality/value Though there are many articles written about the maker movement and libraries, this study contributes to the growing body of research on makerspaces in higher education, with particular focus on a library at a liberal arts university.

Migraine is a debilitating disease that affects almost 15% of the population worldwide and is the first cause of disability in people under 50 years of age, yet its etiology and pathophysiology remain incompletely understood. Recently, small molecules and therapeutic antibodies that block the calcitonin gene-related peptide (CGRP) signaling pathway have reduced migraine occurrence and aborted acute attacks of migraine in clinical trials and provided prevention in patients with episodic and chronic migraine. Heterogeneity is present within each diagnosis and patient's response to treatment, suggesting migraine as a final common pathway potentially activated by multiple mechanisms, e.g., not all migraine attacks respond to or are prevented by anti-CGRP pharmacological interventions. Consequently, other unique mechanisms central to migraine pathogenesis may present new targets for drug development. Pituitary adenylate cyclase-activating peptide (PACAP) is an attractive novel target for treatment of migraines. We generated a specific, high-affinity, neutralizing monoclonal antibody (ALD1910) with reactivity to both PACAP38 and PACAP27. In vitro, ALD1910 effectively antagonizes PACAP38 signaling through the pituitary adenylate cyclase-activating peptide type I receptor, vasoactive intestinal peptide receptor 1, and vasoactive intestinal peptide receptor 2. ALD1910 recognizes a nonlinear epitope within PACAP and blocks its binding to the cell surface. To test ALD1910 antagonistic properties directed against endogenous PACAP, we developed an umbellulone-induced rat model of neurogenic vasodilation and parasympathetic lacrimation. In vivo, this model demonstrates that the antagonistic activity of ALD1910 is dose-dependent, retaining efficacy at doses as low as 0.3 mg/kg. These results indicate that ALD1910 represents a potential therapeutic antibody to address PACAP-mediated migraine.

The costs associated with implementing evidence-based programs for pediatric obesity contribute to a lack of widespread adoption. This study examined the costs of preparing to implement the Family Check-Up 4 Health (FCU4Health), a family-centered behavioral program for the prevention of pediatric obesity and excess weight gain in primary care. Budget impact analysis was used to estimate the cost of preparing to implement FCU4Health (i.e., the activities to prepare for, but prior to, offering the service to families). Electronic cost capture methods were used to prospectively track personnel time associated with implementation preparation activities. We also estimated the cost of replicating these preparatory activities to inform future decisions to adopt the program and associated budgetary planning. The total cost of FCU4Health implementation preparation in three clinics and developing delivery materials and infrastructure was $181,768, for an average of $60,589 per clinic. Over two thirds of the total cost were personnel related, the largest of which was associated with the time spent developing automated fidelity coding for monitoring (20%), developing and tailoring clinical materials (16%), and training FCU4Health coordinators (15%). Due to these development costs associated with an initial implementation, that we anticipate would not be repeated in full, we estimated the cost to prepare FCU4Health for implementation in a future initiative will range from $15,195 to $17,912 per clinic. This study is a critical step towards equipping decision-makers with comprehensive short-term information about expected costs that are incurred immediately after choosing to adopt an evidence-based program.

Plasmon resonant grating structures provide an effective platform for distinguishing between the effects of plasmon resonant excitation and bulk metal absorption via interband transitions. By simply rotating the polarization of the incident light, we can switch between resonant excitation and non-resonant excitation, while keeping all other parameters of the measurement constant. With light polarized perpendicular to the lines in the grating (i.e., TE-polarization), the photocatalytic reaction rate (i.e., photocurrent) is measured as the angle of the incident laser light is tuned through the resonance with the grating. Here, hot holes photoexcited in the metal are used to drive the oxygen evolution reaction (OER), producing a measurable photocurrent. Using TE-polarized light, we observe sharp peaks in the photocurrent and sharp dips in the photoreflectance at approximately 9° from normal incidence, which corresponds to the conditions under which there is good wavevector matching between the incident light and the lines in the grating. With light polarized parallel to the grating (i.e., TM), we excite the grating structure non-resonantly and there is no angular dependence in the photocurrent or photoreflectance. In order to quantify the lifetime of these hot carriers, we performed transient absorption spectroscopy of these plasmon resonant grating structures. Here, we observe one feature in the spectra corresponding to interband transitions and another feature associated with the plasmon resonant mode in the grating. Both features decay over a time scale of 1-2 ps. The spectral responses of grating structures fabricated with Ag, Al, and Cu are also presented.