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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.

Purpose: Directed attention and habituation are key concepts pertaining to clinical intervention for bothersome tinnitus. Directed attention is the strategy of distracting attention away from the tinnitus. Habituation is the process of learning to stop paying attention to stimuli that are irrelevant or meaningless. Although tinnitus may be intrusive, it usually does not reflect some underlying condition requiring medical attention. Tinnitus in most instances is therefore considered an irrelevant, meaningless stimulus that is best treated by facilitating habituation to the phantom sound. This tutorial describes directed attention and habituation and how they relate to major behavioral methods of tinnitus intervention. Method: Arguably, the four major behavioral methods of tinnitus intervention with the strongest research evidence are cognitive behavioral therapy (CBT), tinnitus retraining therapy (TRT), tinnitus activities treatment (TAT), and progressive tinnitus management (PTM). Each of these four methods was evaluated to determine the role of directed attention as a treatment strategy and habituation as a treatment goal. Results: All four of the methods (CBT, TRT, TAT, and PTM) utilize some form of directed attention as a component of their counseling. Habituation is the explicit or implicit goal of each of these methods. Conclusions: Directed attention and habituation are essential concepts for all of the major methods of behavioral intervention for tinnitus that were studied. It would therefore seem appropriate to include directed attention as a universal treatment strategy for bothersome tinnitus. Likewise, the commonality of habituation as the objective of treatment would suggest that habituation should be the universal goal of any method that is intended to mitigate the emotional and functional effects of tinnitus.

Purpose: The Tinnitus Screener was introduced in 2015 as a four-item algorithmic instrument to assess the temporal characteristics of a person’s reported tinnitus. The Tinnitus Screener was then revised as a six-item version to include a new temporal category and to capture tinnitus duration (acute < 6 months vs. chronic ≥ 6 months). When contrasted with audiologist assessment, the four-item Tinnitus Screener was determined to be highly valid, but the short-term reliability of either version remained unknown. The present analysis focused on determining the test–retest reliability of the six-item Tinnitus Screener. Additionally, we sought to determine whether reliability differed by respondent age, sex, military status, and hearing loss. Method: The Tinnitus Screener was administered to 190 military Service members and 250 military Veterans at two time points separated by 7–31 days. Our analysis focused on test–retest reliability of responses as measured by the kappa coefficient, overall and within subsamples. Percent agreement of tinnitus categorization (temporal categories) and classification (positive/negative) between the two time points was also evaluated. Results: Constant or intermittent tinnitus was found in 31% of Service members and 53% of Veterans. Overall, kappa reliability coefficients were high, near .80, indicating substantial reliability. The majority (96%) of reliability coefficients for the Tinnitus Screener within subsamples were similarly high, ranging from .68 to .88. Conclusions: The updated version of the Tinnitus Screener is shown to be a reliable instrument. The Tinnitus Screener is recommended to inform clinical decision making by determining the temporal characteristics of tinnitus.

In the past two decades, the effort toward reducing poverty and its dimensions has increased in middle and low-income countries by introducing diverse social protection programmes. In Nigeria, for instance, various successive regimes have experimented with myriads of programmes targeted at poverty alleviation. Yet, in 2018, Nigeria was named the world's poverty capital, with about 87 million citizens living in extreme poverty. This data could be because economists, the World Bank, and other development organizations have stereotyped the concept of poverty as income, consumption, and wealth without paying attention to the "poverty mentality". As a result, governments often instinctively neglect the influence of the "poverty mentality" on the part of beneficiaries of poverty alleviation programmes when initiating social protection policy framework for the country. However, from the literature reviewed, a "poverty mentality" often leads to poor financial decisions and deadweight spending. Accordingly, this research article recommends a new international poverty order (NIPO) by dealing with multidimensional poverty and "poverty mentality" through investment education and value reorientation.

Purpose: The purpose of this study was to examine progressive tinnitus management (PTM) Level 3 skill utilization among Veterans in the Bay Pines Veterans Affairs Healthcare System 6–10 years after completing the PTM workshops. Method: In fiscal year 2020, the Tinnitus Workshop Follow-Up form was mailed to Veterans who completed the workshops during fiscal years 2010–2014. Veterans were identified as receiving care via the traditional face-to-face method or clinical video telehealth (CVT). Data were compiled to determine which, if any, PTM skills were being used 6–10 years later and the impact on self-reported ratings of well-being. Results: More than half of the respondents reported using all four self-management skills up to 10 years postcompletion; relaxation was utilized by more Veterans than the other three skills. Approximately 69% reported improved ability to control reactions to tinnitus. At least half reported ratings of improved well-being. Eighty-eight percent of the respondents said they would recommend the workshops to someone with bothersome tinnitus. Veterans who received care via CVT reported using fewer skills than those who received care face-to-face; however, the CVT respondents reported the same or slightly better ability to cope with tinnitus, less bothersome tinnitus, and improved ratings of well-being. Finally, most participants who responded to an open-ended question about their workshop experience reported it as positive. Conclusions: This clinical focus project suggests that PTM Level 3 skills continue to be utilized up to 10 years after participation in the workshops. Although there were reductions in the number of skills used, Veterans' ability to manage reactions to tinnitus and improvement in self-reported ratings of well-being indicate successful ongoing tinnitus management efforts. Respondents who received care via CVT did not report lower self-reported ratings of well-being or appear less likely to recommend Level 3 group PTM to other Veterans with bothersome tinnitus.

Purpose: For some people, exposure to everyday sounds presents a significant problem. The purpose of this tutorial was to define and differentiate between the various sound tolerance conditions and to review some options for their clinical management. Method: We informally reviewed the literature regarding sound tolerance conditions. The terminology and definitions provided are mostly consistent with how these terms are defined. However, many inconsistencies are noted. Methods of assessment and treatment also differ, and different methodologies are briefly described. Results: Hyperacusis describes physical discomfort or pain when any sound reaches a certain level of loudness that would be tolerable for most people. Misophonia refers to intense emotional reactions to certain sounds (often body sounds such as chewing and sniffing) that are not influenced by the perceived loudness of those sounds. Noise sensitivity refers to increased reactivity to sounds that may include general discomfort (annoyance or feeling overwhelmed) due to a perceived noisy environment, regardless of its loudness. Phonophobia, as addressed in the audiology profession, describes anticipatory fear of sound. Phonophobia is an emotional response such as anxiety and avoidance of sound due to the “fear” that sound(s) may occur that will cause a comorbid condition to get worse (e.g., tinnitus) or the sound itself will result in discomfort or pain. (Note that phonophobia is a term used by neurologists to describe “migraineur phonophobia”—a different condition not addressed herein.) Conclusions: The literature addresses sound tolerance conditions but reveals many inconsistencies, indicating lack of consensus in the field. When doing an assessment for decreased sound tolerance, it is important to define any terms used so that the patient and all health care professionals involved in the care of the patient are aligned with the goals of the treatment plan. Treatment generally involves gradual and systematic sound desensitization and counseling. Supplemental Material: https://doi.org/10.23641/asha.20164130

This study investigated the impact of electricity supply on manufacturing output in Nigeria using data from 1980 to 2019. By augmenting the endogenous growth model production function with key variables affecting manufacturing sector output, such as exchange rate and technology, which previous studies failed to capture. The result of the autoregressive distributed lag (ARDL) model revealed that electricity supply has a negative and insignificant relationship with the manufacturing sector output. Conversely, technology has a positive and significant relationship with manufacturing sector output in the short run. Thus, it was recommended that an adequate and stable supply of electricity and deploying modern technology should be on the front burner of the country's development policy. This steady supply will not only enhance the growth of the manufacturing sector but also lead to inclusive growth in terms of reducing poverty and unemployment in the Nigerian economy and promoting rapid economic growth.

This study evaluated the influence of tinnitus and hearing loss on the functional status of military Service members and Veterans.Participants completed audiologic testing and self-report instruments to assess tinnitus, hearing, and general functioning. We conducted multiple linear regression analyses using cross-sectional data with functional status as the dependent variable. The primary independent variables were tinnitus and average low-, high-, and extended high-frequency hearing thresholds. Secondary independent variables were subjective tinnitus severity and hearing difficulties. Each of the independent variables was modelled separately for Service members and Veterans; covariates for each multivariable model were identifiedData were analysed from 283 Service members and 390 Veterans.After controlling for potential confounders, presence of tinnitus, tinnitus severity, average low-frequency hearing thresholds, and subjective hearing difficulties were significantly associated with functional status in Service members and Veterans.These results suggest that tinnitus and poorer low-frequency hearing, and the perceived severity of tinnitus and hearing difficulties, may be associated with poorer functional status among Service members and Veterans.

Purpose: Tinnitus is a highly prevalent condition that can severely reduce health functioning. In spite of extant clinical practice guidelines (CPGs), implementation of these CPGs is relatively uncommon. As a result, patients seeking professional services for tinnitus often have no assurance of receiving evidence-based care. The purpose of this tutorial was to clarify the evidence for sound therapy so that it may be included in future CPGs for tinnitus. Method: “Best clinical evidence” is obtained from high-quality systematic reviews, which are generally considered the highest level of evidence. Our review of recent, comprehensive, high-quality systematic reviews of interventions for tinnitus concludes that cognitive behavioral therapy is the only effective intervention, though the strength of evidence was generally rated as low in these reviews. Although trials of sound therapy for tinnitus have been included in these reviews, they have been rated as having high risk of bias (RoB) and not included in syntheses or rated as insufficient strength of evidence. Results: Conclusions from these and other reviews have influenced recommendations made in CPGs for tinnitus. These conclusions, however, can make it appear that an intervention for tinnitus is not effective, even if the opposite is true. We contend that the strict inclusion criteria for these reviews are counterproductive and have the effect of obscuring decades of evidence demonstrating the clinical effectiveness of sound therapies for tinnitus. Ultimately, this process has resulted in many patients not receiving sound therapy, despite what should be sufficient evidence that this is an effective form of intervention. Conclusion: If we rely on systematic reviews using contemporary RoB assessment criteria for studies published prior to these reporting guidelines, then we risk excluding important conclusions regarding interventions that could help patients in need.

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

Transactions of the Leicestershire Archaeological and Historical Society, 13, 155-198, When the fiscal survey known as the Domesday Book was compiled, two churches, a hundred and ten houses, and certain other properties in the borough of Leicester, and more than seventy manors in the county, were held by Hugh de Grentemesnil, a Norman baron who had fought at Hastings and had taken a leading part in the subjugation of England. This powerful nobleman was thus by far the greatest landowner in Leicester� shire, and his estates formed the nucleus of the honour attached to the earldom of Leicester, which was created in the next century, when the local pre-eminence and possessions of the Grentemesnils passed to the still more important family of Beaumont, from which Simon de Montfort, the last of the pre- Lancastrian earls, derived his right of succession.

Transactions of the Leicestershire Archaeological and Historical Society, 10, 382-394, An account of the Manor of Hinckley based on surviving 18th century documents.

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

Dandruff is a pervasive chronic condition which negatively impacts quality of life. Effective treatment requires efficient delivery of scalp benefit agents that control commensal scalp Malassezia levels. Delivery of benefit agents from shampoos requires balancing many technical parameters to achieve the desired outcome without sacrificing secondary paraters such as cosmetic attributes.To develop formulation technologies that increase the shampoo delivery efficiency of the scalp benefit agent piroctone olamine (PO). Increased delivery should result in increased anti-dandruff efficacy.Micellar stability and association parameters were quantified via dynamic surface tension and NMR diffusion parameters, respectively. PO delivery has been assessed in vivo both on the scalp surface and follicular infindibula using extraction procedures and analytical analysis. Clinical anti-dandruff efficacy was assessed for an advanced delivery technology prototype in comparison to standard delivery technology.Shampoo prototypes have been developed that increase the delivery efficiency of PO. Both surfactant- and polymer coacervate-based approaches have been developed. Decreased micellar stability results in weaker association between PO and micelles, resulting in more efficient PO retention on the scalp surface and delivery to the infundibula. Increased charge density of cationic polymers optimizes coacervation enabling improved PO delivery as well. Increased PO delivery has been shown clinically to result in higher anti-dandruff efficacy as measured by both visible flakes and underlying biomarkers.Increased efficiency PO delivery shampoos have been developed by optimization of both surfactant and coacervate parameters. The increased deposition efficiency results in significantly more products with significantly greater anti-dandruff efficacy.

Purpose: Hyperacusis is the most common of the different types of sound tolerance conditions. It has been defined as physical discomfort or pain when any sound reaches a certain level of loudness that would be comfortable for most people. Because hyperacusis and tinnitus occur together so often, it has been theorized that they have a common neural mechanism. A leading contender for that mechanism is enhancement of auditory gain. The purpose of this tutorial is to review the evidence that sound/acoustic therapy can reduce auditory gain and, thereby, can increase loudness tolerance for people with hyperacusis and/or suppress the percept of tinnitus. Method: The scientific literature was informally reviewed to identify and elucidate relationships between tinnitus, hyperacusis, sound therapy, and auditory gain. Results: Evidence exists, both in animal and human studies, that enhanced auditory gain is associated with hyperacusis and tinnitus. Further evidence supports the theory that certain forms of sound therapy can reduce neural hyperactivity, thereby reducing auditory gain. The evidence for sound therapy reducing auditory gain is stronger for hyperacusis than it is for tinnitus. Conclusions: Based on results from numerous studies, sound therapy clearly has application as a method of desensitization for hyperacusis. Enhanced auditory gain might be responsible for tinnitus, but other mechanisms have been theorized. A review of the relevant literature leads to the conclusion that some form(s) of sound therapy has the potential to suppress or eliminate tinnitus on a long-term basis. Systematic research is needed to evaluate this premise.

Audiologists' role in providing care for tinnitus typically includes conducting an audiologic evaluation, fitting hearing aids when appropriate, assessing the impact of tinnitus, and facilitating use of sound to improve quality of life with tinnitus when appropriate. Cognitive behavioral therapy (CBT) is consistently judged by systematic reviews as having the strongest evidence relative to other therapies for improving quality of life with tinnitus. Because audiologists are already playing an active role in providing care for tinnitus, and the relative paucity of behavioral health providers who are experienced in implementing CBT for tinnitus, a logical question is whether audiologists can provide CBT and whether it is within their scope of practice. In this article, we present both sides of the argument as to whether audiologists can provide CBT and we make recommendations for appropriate administration of CBT for tinnitus management.