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One of the challenges facing agricultural sector development in Nigeria is inadequate financing by the government and financial institutions. This poor agricultural funding has an impact on economic activities. Thus, this study investigated the connection between agricultural funding and economic performance in Cross Rivers State's Obudu Local Government Area (LGA). The survey study methodology was employed, and a questionnaire was used as its primary data source, combined with a stratified sample technique. The targeted population was restricted to farmers and agriculturalists in the study area. Descriptive statistics, such as frequency and percentages tables, were calculated, and the data gathered from the questionnaire were compiled, computed, and analysed. The results of hypothesis testing showed a relationship between agricultural finance and economic performance, as well as a connection between agricultural credit schemes and agricultural sector expansion, using analysis of variance (ANOVA) as the statistical technique. They also showed that credit programmes for agricultural finance encourage the expansion of the agricultural sector, which improves economic performance, as manifested in economic growth and development. The study recommends, firstly, that the government release grants to farmers at regular intervals to support their activities. Secondly, it is necessary to raise the level and size of agricultural loans through the reduction of interest rates to allow for more economic development in the country. The government should implement an effective and efficient supervisory framework to monitor interest rate regulation within the agricultural loan policy.

To examine associations between non-otologic medical conditions and auditory dysfunction. Cross-sectional analysis of baseline data from the Noise Outcomes in Service members Epidemiology (NOISE) study. Logistic regression was used to estimate the association between medical conditions (0, 1, and 2 or more conditions) and auditory dysfunction (hearing loss pure tone average ≥20 dB HL and tinnitus), adjusting for key confounders including noise exposure. Secondarily, the association between specific medical conditions and auditory dysfunction was examined. All variables were self-reported. United States military Veterans (n = 580) with mean age 34.1 years (standard deviation = 9.2), who were within approximately 2.5 years of separation from service. Compared to Veterans reporting no medical conditions, Veterans reporting two or more had increased odds on low-frequency hearing loss and on tinnitus but not on high or extended-high frequency hearing loss. Furthermore, specific conditions sleep disorder and arthritis were associated with auditory dysfunction. Non-otologic medical conditions were associated with low-frequency hearing loss and tinnitus in this sample of young Veterans. This suggests medical conditions may play a role in Veterans’ hearing health. Whether management of medical conditions earlier in life reduces the risk of hearing loss and tinnitus requires further study.

Supplementary Figure S2 shows two cases of patients treated at the RP2D. IHC at Clarient for p-ERK, p27 and Ki-67 were assessed for PD effect using monoclonal rabbit phospho-p44/42 MAPK (ERK1/2), 20G11 Clone; monoclonal mouse anti-Ki67, MIB-1 clone; and monoclonal mouse anti-p27, SX53G8 clone. In (A), the patient is a 56-year old female patient with rectal neuroendocrine cancer who is KRAS and BRAF wild-type. No differences in staining for the 3 biomarkers were observed when baseline and Day 28 samples were compared. In (B), the patient is a 26-year old male patient with hepatocellular carcinoma with unknown mutational status. No differences in staining for Ki-67 or p27 were observed when baseline and Day 28 samples were compared. The p-ERK staining is poor quality and not interpretable. Abbreviations: IHC, immunohistochemistry; PD, pharmacodynamics; RP2D, recommended phase 2 dose

LY3295668 chemical characterization

Supplementary Materials and Methods

Although Aurora A, B, and C kinases share high sequence similarity, especially within the kinase domain, they function distinctly in cell-cycle progression. Aurora A depletion primarily leads to mitotic spindle formation defects and consequently prometaphase arrest, whereas Aurora B/C inactivation primarily induces polyploidy from cytokinesis failure. Aurora B/C inactivation phenotypes are also epistatic to those of Aurora A, such that the concomitant inactivation of Aurora A and B, or all Aurora isoforms by nonisoform–selective Aurora inhibitors, demonstrates the Aurora B/C-dominant cytokinesis failure and polyploidy phenotypes. Several Aurora inhibitors are in clinical trials for T/B-cell lymphoma, multiple myeloma, leukemia, lung, and breast cancers. Here, we describe an Aurora A–selective inhibitor, LY3295668, which potently inhibits Aurora autophosphorylation and its kinase activity in vitro and in vivo, persistently arrests cancer cells in mitosis, and induces more profound apoptosis than Aurora B or Aurora A/B dual inhibitors without Aurora B inhibition–associated cytokinesis failure and aneuploidy. LY3295668 inhibits the growth of a broad panel of cancer cell lines, including small-cell lung and breast cancer cells. It demonstrates significant efficacy in small-cell lung cancer xenograft and patient-derived tumor preclinical models as a single agent and in combination with standard-of-care agents. LY3295668, as a highly Aurora A–selective inhibitor, may represent a preferred approach to the current pan-Aurora inhibitors as a cancer therapeutic agent.

shRNA suppressor screening data for H446 and MDA-MB-468 cells (tabs 1, 2) and RNA expression level associations with LY3295668 Abs IC50 values from 493 cancer cell lines (tab 3).

Supplementary Tables

Supplementary figures

Supplementary Figure S1. Validation of BRAF deletion in BxPC-3 cells by Sanger's sequencing method. Supplementary Figure S2. BRAF deletion (deltaBRAF), but not WT BRAF, is able to transform cells. Supplementary Figure S3. Validation of in situ PLA in HeLa and HEK293 cells. Supplementary Figure S4. Phospho-CRAF and MAPK activation in selected tumor cells with BRAF alteration or KRAS mutation. Supplementary Figure S5. Phospho-MEK and ERK inhibition by dabrafenib in tumor cells harboring BRAF deletion. Supplementary Figure S6. In vitro effects of MAPK inhibitors on tumor cells harboring BRAF deletions. Supplementary Table S1. Novel somatic BRAF in-frame deletions from cancer cell lines and patient samples. Supplementary Figure S7. LY3009120, but not vemurafenib, exhibited significant tumor growth inhibition and regression in lung and pancreatic tumor xenograft models harboring the BRAF deletions without significant body weight loss. Supplementary Table S2. IC50 of LY3009120 and vemurafenib against tumor cells with atypical BRAF mutations.

Supplementary Figures

Purpose: To evaluate the antitumor efficacy of cetuximab in combination with LSN3074753, an analog of LY3009120 and pan-RAF inhibitor in 79 colorectal cancer patient-derived xenograft (PDX) models.Experimental Design: Seventy-nine well-characterized colorectal cancer PDX models were employed to conduct a single mouse per treatment group (n = 1) trial.Results: Consistent with clinical results, cetuximab was efficacious in wild-type KRAS and BRAF PDX models, with an overall response rate of 6.3% and disease control rate (DCR) of 20.3%. LSN3074753 was active in a small subset of PDX models that harbored KRAS or BRAF mutations. However, the combination treatment displayed the enhanced antitumor activity with DCR of 35.4%. Statistical analysis revealed that BRAF and KRAS mutations were the best predictors of the combinatorial activity and were significantly associated with synergistic effect with a P value of 0.01 compared with cetuximab alone. In 12 models with BRAF mutations, the combination therapy resulted in a DCR of 41.7%, whereas either monotherapy had a DCR of 8.3%. Among 44 KRAS mutation models, cetuximab or LSN3074753 monotherapy resulted in a DCR of 13.6% or 11.4%, respectively, and the combination therapy increased DCR to 34.1%. Molecular analysis suggests that EGFR activation is a potential feedback and resistant mechanism of pan-RAF inhibition.Conclusions: MAPK and EGFR pathway activations are two major molecular hallmarks of colorectal cancer. This mouse PDX trial recapitulated clinical results of cetuximab. Concurrent EGFR and RAF inhibition demonstrated synergistic antitumor activity for colorectal cancer PDX models with a KRAS or BRAF mutation. Clin Cancer Res; 23(18); 5547–60. ©2017 AACR.

S1 and S2

Supplementary Table S1 and S2

Purpose Evidence suggests that military blast exposure may lead to self-reported hearing difficulties despite audiometrically normal hearing. Research identifying potential mechanisms of this association remains limited. The purpose of this article is to evaluate the associations between blast, posttraumatic stress disorder (PTSD), and self-reported hearing difficulty, and to examine PTSD as a possible mediator of the association between blast exposure and hearing difficulty. Method We used baseline data from the Noise Outcomes in Service members Epidemiology (NOISE) study ( n = 477). Participants in this study undergo a comprehensive hearing, and tinnitus if applicable, evaluation and complete a large number of surveys. Pertinent data extracted from these surveys included information on participant's demographics, military service history, including exposure to blast, and health conditions such as symptoms of PTSD. Using regression models and following a formal causal mediation framework, we estimated total associations, natural direct and indirect associations, and percent mediated. Results We found that individuals with blast exposure had higher prevalence of both probable PTSD and self-reported hearing difficulty than individuals who were not blast exposed. Compared with participants without blast exposure, those with blast exposure had twice the prevalence of self-reported hearing difficulty, with 41% of the association mediated through probable PTSD. Conclusion As PTSD is a possible mediator of the association between blast exposure and hearing difficulty, Service members and Veterans with normal pure-tone hearing sensitivity who report hearing difficulties and a history of blast exposure may benefit from evaluation for PTSD symptoms. Supplemental Material https://doi.org/10.23641/asha.16674247

Tinnitus is commonly referred to as "ringing in the ears." Epidemiologic studies highlight challenges associated with clinical determination of tinnitus and ascertainment of its etiology, functional effects, temporal characteristics, psychoacoustic parameters, and risk factors. Because no standards exist for capturing these factors as measures, direct comparison of data between studies is not possible. This report suggests terminology and definitions to promote standardization, with a brief overview of findings from selected population-based epidemiologic studies. Tinnitus-specific data are presented from the Noise Outcomes in Servicemembers Epidemiology study. Further epidemiologic studies are needed to develop tinnitus treatment and a cure for this chronic condition.

Background: Immune responses to vaccination are a known trigger for a new onset of glomerular disease or disease flare in susceptible individuals. Mass immunization against SARS-CoV-2 in the COVID-19 pandemic provides a unique opportunity to study vaccination-associated autoimmune kidney diseases. In the recent literature, there are several case reports demonstrating a temporal association of SARS-CoV-2 immunization and kidney diseases. Methods: Here, we present a series of 29 cases of biopsy-proven glomerular disease in patients recently vaccinated against SARS-CoV-2 and identified patients who developed a new onset of IgA nephropathy, minimal change disease, membranous nephropathy, ANCA-associated glomerulonephritis, collapsing glomerulopathy, and diffuse lupus nephritis diagnosed on kidney biopsies post-immunization, as well as recurrent ANCA-associated glomerulonephritis. This included 28 cases of de novo glomerulonephritis within native kidney biopsies and one disease flare in an allograft. Results: The patients with collapsing glomerulopathy were of African American descent and had two APOL1 genomic risk alleles. A brief literature review of case reports and small series is also provided to include all reported cases to date (n=52). The incidence of induction of glomerular disease in response to SARS-CoV-2 immunization is unknown, however, there was no overall increase in incidence of glomerular disease when compared to the two years prior to the COVID-19 pandemic diagnosed on kidney biopsies in our practice. Conclusions: This suggests that glomerulonephritis in response to vaccination is rare, although should be monitored as a potential adverse event.

Purpose A need exists to investigate the short- and long-term impact of noise exposures during and following military service on auditory health. Currently available questionnaires are limited in their ability to meet this need because of (a) inability to evaluate noise exposures beyond a limited time frame, (b) lack of consensus on scoring, (c) inability to assess impulse exposures (e.g., firearm use), (d) lack of a single questionnaire that assesses both military and nonmilitary exposures, and (e) lack of validity and reliability data. To address these limitations, the Lifetime Exposure to Noise and Solvents Questionnaire (LENS-Q) was developed. The purpose of this report is to describe the development and initial validation of the LENS-Q as a measure of self-reported noise exposure. Method Six hundred ninety participants, consisting of current Service members and recently military-separated (within about 2.5 years) Veterans, completed the LENS-Q, additional study questionnaires, and comprehensive audiometric testing. Noise exposure scores were computed from LENS-Q responses using a simple scoring algorithm that distinguishes between different cumulative levels of exposure and allows for the inclusion of both continuous and impulse noise exposures. Results The LENS-Q demonstrates good construct validity as evidenced by measures of hearing loss, tinnitus, and subjective hearing difficulties all increasing with an increase in noise exposure scores. A logistic regression, adjusting for age and sex, revealed that participants in the highest exposure group were 2.4–3.9 times more likely to experience hearing loss, 2.7–2.8 times more likely to experience tinnitus, and 3.0–3.7 times more likely to report hearing difficulties compared with individuals in the lowest exposure group. Conclusions The LENS-Q captures noise exposure over an individual's lifetime and provides an alternative scoring metric capable of representing exposure to both continuous and impulse noise. Findings suggest that the LENS-Q is a valuable tool for capturing and measuring both military and nonmilitary noise exposure. Supplemental Material https://doi.org/10.23641/asha.14582937

Current research on blast and other injuries sustained by United States Service members and Veterans of the Iraq and Afghanistan Wars reveals a multitude of auditory complaints linked to exposures experienced during these conflicts. Among these complaints is decreased sound tolerance, which refers to a class of auditory-related problems including physical and/or psychological reactions to aspects of everyday sounds. Limited attention has been given to the possible relationship between blast exposure and decreased sound tolerance in Service members and Veterans, which is the purpose of this report. Baseline data were gathered and analyzed from 426 Service members (n = 181) and Veterans (n = 245) who participated in the Noise Outcomes in Servicemembers Epidemiology (NOISE) Study. Logistic regression analyses were performed to generate odds ratios (ORs) with 95% confidence intervals (CIs) for each group, adjusted for age and sex. Of those who reported blast exposure, 33% of Service members (adjusted OR = 1.4; CI = 0.7–2.8) and 48% of Veterans (adjusted OR = 1.9; CI = 1.1–3.3) reported decreased sound tolerance. Among Service members and Veterans who did not report blast exposure, 28% and 34% respectively, also reported decreased sound tolerance. Overall, blast exposure increased the likelihood of participants reporting decreased sound tolerance. The strength of this association was significant in Veterans.

Objectives The Noise Outcomes in Servicemembers Epidemiology (NOISE) Study is obtaining longitudinal data to evaluate the effects of noise and other exposures on auditory function in military personnel. A gap in the literature is the lack of studies concerning how active-duty Service members might be impacted by having tinnitus. The present study reports NOISE Study data that address this gap. Methods Data are reported from current Service members and recently-separated (within 2.5 years) Veterans, enabling a direct comparison of results between active and post-military samples. Data were collected from two sites: VA Portland Health Care System, Portland, OR and Department of Defense Hearing Center of Excellence, San Antonio, TX. Participants completed comprehensive audiometric testing and numerous questionnaires. Results Results are presented from n = 428 participants across the two sites, including 246 Veterans and 182 Service members. The data reveal that, for both Service members and Veterans, the presence of tinnitus has effects on job performance, concentration, anxiety, depression, and sleep. Conclusions This study has revealed that, for these samples of study participants, tinnitus has an impact on military Service members that is comparable to how it affects Veterans who have completed their military service within the previous 2.5 years.

We describe a 23-year-old woman with previous right temporal lobe surgeries for underlying cortical dysplasia, presenting with drug-resistant right hemispheric seizures and epilepsia partialis continua (EPC). After anti-seizure medication adjustments, she developed focal status epilepticus with progressive EEG and neuroimaging changes. Cerebrospinal fluid and serum autoimmune panels were negative except for an elevated serum acetylcholine-receptor antibody titer, but she underwent immunosuppressive therapy. Stereotactic-EEG evaluation demonstrated multifocal independent ictal patterns in the right hemisphere. Rasmussen's Syndrome was confirmed by brain biopsy, and a hemispherectomy was performed. This patient demonstrates the rare association of adult-onset EPC with cortical dysplasia, precipitously evolving into Rasmussen's Syndrome., Highlights • Rasmussen's Syndrome (RS) can be associated with focal cortical dysplasia. • Autoimmunity underlies evolution of new-onset EPC in the setting of chronic focal epilepsy, and support a diagnosis of RS. • Hemispherectomy can be an effective intervention in adult-onset RS.

Objective Compare the relative efficacy of DesyncraTM and Cognitive Behavioural Therapy (CBT). Design and study sample Sixty-one participants were randomly assigned to receive either DesyncraTM (n = 29) or CBT (n = 32). Randomisation included stratification regarding current hearing aid (HA) use. Depending on group assignment, participants attended approximately 7-12 visits. Tinnitus distress was measured using the Tinnitus Questionnaire (TQ). Results Mean TQ scores decreased post-baseline from 5-15 points across treatment arms and strata. Model-based findings for the no-HA stratum showed a difference of -2.0 TQ points favouring Desyncra at 24-weeks, with a 90% posterior interval varying from -5.4 points favouring Desyncra to 0.8 TQ points favouring CBT. For the HA stratum, results show a difference of -1.0 TQ points favouring Desyncra, with a 90% posterior interval ranging from -4.7 points favouring Desyncra to 2.9 points favouring CBT. Conclusions The difference between Desyncra and CBT on average showed greater improvement with Desyncra in the no-HA stratum by about 2 TQ points. To the extent that the study sample represents a clinical population and recognising the assumptions in the design and analysis, these results suggest Desyncra is just as effective or more so than CBT in reducing tinnitus distress.

Introduction Tinnitus is prevalent among Service members and Veterans and is often comorbid with mental health disorders. Associations between the severity of individuals’ tinnitus and mental health symptoms are not well described. Materials and Methods We conducted a population-based survey of a stratified random sample of 1,800 Veterans diagnosed with tinnitus. We used the Tinnitus Functional Index to measure tinnitus severity and the Primary Care-Posttraumatic Stress Disorder (PTSD) screen and the Hospital Anxiety and Depression Scale to assess PTSD, depression, and anxiety. Descriptive statistics and bivariable and multivariable regression models were used to estimate associations between Veterans’ tinnitus severity and mental health symptoms. Inverse probability weights were used to account for sample stratification and survey non-response. Multivariable odds ratios (ORs) and 95% confidence intervals (CIs) controlled for Veterans’ demographics, military history, and health diagnoses. Results A total of 891 Veterans completed surveys (adjusted response rate = 53%). Large proportions rated their tinnitus as severe (29.4%; 95% CI: 27.2-31.6) or very severe (18.7%; 95% CI: 16.8-20.5). In multivariable regression models, and compared with Veterans with none/mild tinnitus, the likelihood of screening positive for PTSD was increased for those who reported moderate (OR = 4.0; 95% CI: 1.6-10.3), severe (OR = 7.5; 95% CI: 3.1-18.5), or very severe (OR = 17.5; 95% CI: 4.4-70.0) tinnitus. Similarly, Veterans’ likelihood of positive depression screens were elevated for those with moderate (OR = 2.6; 95% CI: 1.1-5.9), severe (OR = 3.0; 95% CI: 1.4-6.5), or very severe (OR = 15.5; 95% CI: 4.3-55.5) tinnitus, as was the likelihood of positive anxiety screens for those with severe (OR = 2.6; 95% CI: 1.1-6.3) or very severe (OR = 13.4; 95% CI: 4.0-44.3) tinnitus. Conclusions Mental health symptoms are strongly associated with Veterans’ tinnitus severity. A better understanding of the interplay between these conditions may help improve the provision of interdisciplinary (Audiology and Mental Health) care for Service members and Veterans.

Purpose Although tinnitus is highly prevalent among patients receiving audiology services, audiologists are generally untrained in tinnitus management. Audiology graduate programs, as a rule, do not provide comprehensive instruction in tinnitus clinical care. Training programs that do exist are inconsistent in their recommendations. Furthermore, no standards exist to prevent the delivery of unvetted audiologic services, which can be expensive for patients. Patients seeking professional services by an audiologist, therefore, have no basis upon which to be assured they will receive research-based care. The purpose of this article is to describe the current status of tinnitus management services that exist within the general field of audiology and to suggest specific approaches for improving those services. Conclusion Audiologists may be in the best position to serve as the primary health care providers for patients experiencing tinnitus. Tinnitus care services by audiologists, however, must achieve a level of evidence-based standardization.

Purpose The aim of this study was to determine if a customized stimulus from the Otoharmonics Levo System reduces tinnitus perceptions and reactions for people with bothersome tinnitus. Method Sixty participants were randomized to 1 of 3 groups that used sound therapy devices during sleep that differed in their acoustic stimulus: (a) tinnitus-matched (TM), (b) noise stimulus (NS), and (c) bedside sound generator (BSG). Outcome measures were the Tinnitus Functional Index (TFI), numeric rating scale of tinnitus loudness, and tinnitus loudness match. A Bayesian hierarchical model was fit to estimate the differences in treatment efficacy among groups. Results Average tinnitus reactions and perceptions improved across treatment groups. We are at least 87% certain that treatment with TM or NS reduces mean TFI compared to treatment with BSG, with an estimated relative efficacy of 4.5–5 points greater reduction. We are at least 95% certain that treatment with TM results in greater reduction in mean numeric rating scale (NRS) of tinnitus loudness compared to the other groups, with an estimated relative efficacy of about 0.75 points greater reduction. Conclusions This study offers some support for greater average improvement in reactions to tinnitus with TM or NS devices compared to the BSG device. The TM group, compared to the BSG and NS groups, showed a greater reduction in ratings of tinnitus loudness on the NRS on average. Supplemental Material https://doi.org/10.23641/asha.5545759