Comparing Echo-Detection and Echo-Localization in Sighted Individuals.

Echolocation is the ability to gather information from sound reflections. Most previous studies have focused on the ability to detect sound reflections, others on the ability to localize sound reflections, but no previous study has compared the two abilities in the same individuals. Our study compared echo-detection (reflecting object present or not?) and echo-localization (reflecting object to the left or right?) in 10 inexperienced sighted participants across 10 distances (1-4.25 m) to the reflecting object, using an automated system for studying human echolocation. There were substantial individual differences, particularly in the performance on the echo-localization task. However, most participants performed better on the detection than the localization task, in particular at the closest distances (1 and 1.7 m), illustrating that it sometimes may be hard to perceive whether an audible reflection came from the left or right.

Individual differences in the ability to access spatial information in lag-clicks.

It may be difficult to determine whether a dichotic lag-click points to the left or right when preceded by a diotic lead-click. Previous research suggests that this loss of spatial information is most prominent at inter-click intervals (ICIs) <10 ms. However, a study by Nilsson, Tirado, and Szychowska [(2019). J. Acoust. Soc. Am. 145, 512-524] found support for loss of spatial information in lag-clicks at much longer ICIs using a stimulus setup differing from those in previous research. The present study used a setup similar to that of the Nilsson, Tirado, and Szychowska study [(2019). J. Acoust. Soc. Am. 145, 512-524] to measure 13 listeners' ability to lateralize (left versus right) and detect (present versus absent) the lag-click in lead-lag click pairs with ICIs of 6-48 ms. The main finding was distinct individual differences in performance. Some listeners could lateralize lag-clicks all the way down to their detection threshold, whereas others had lateralization thresholds substantially higher than their detection thresholds, i.e., they could not lateralize lag-clicks that they could easily detect. Two such listeners trained for 30 days and managed to improve their lateralization thresholds to reach their detection thresholds, but only at longer ICIs (>20 ms), suggesting different mechanisms underlying lag-click lateralization at short versus long ICIs.

Psychoacoustic evidence for stronger discrimination suppression of spatial information conveyed by lag-click interaural time than interaural level differences.

Listeners have limited access to spatial information in lagging sound, a phenomenon known as discrimination suppression. It is unclear whether discrimination suppression works differently for interaural time differences (ITDs) and interaural level differences (ILDs). To explore this, three listeners assessed the lateralization (left or right) and detection (present or not) of lag clicks with a large fixed ITD (350 µs) or ILD (10 dB) following a diotic lead click, with inter-click intervals (ICIs) of 0.125-256 ms. Performance was measured on a common scale for both cues: the lag-lead amplitude ratio [dB] at 75% correct answers. The main finding was that the lateralization thresholds, but not detection thresholds, were more strongly elevated for ITD-only than ILD-only clicks at intermediate ICIs (1-8 ms) in which previous research has found the strongest discrimination suppression effects. Altogether, these findings suggest that discrimination suppression involves mechanisms that make spatial information conveyed by lag-click ITDs less accessible to listeners than spatial information conveyed by lag-click ILDs.

A Revised Occupational Stress Measure for Popular Musicians: Pilot Test of Validity and Reliability.

OBJECTIVE: Popular (i.e., nonclassical) musicians have higher rates of depression, anxiety, and suicide than the general population. Occupational and financial stress have been suggested to be social determinants of musician mental health burden. A pilot study was conducted to assess the internal consistency and test-retest reliability of a revised measure of popular musician occupational stress and compare the results to those of other, previously validated instruments used in the same survey. METHODS: An online survey was emailed to a convenience sample of 150 musicians who had formerly accessed mental health services through a non-profit organization in Austin, Texas. The survey included a revised Musician Occupational Stress Scale (MOSS), a measure of financial stress, and instruments to screen for clinically significant depression, anxiety, and alcohol misuse. RESULTS: Forty musicians (26.7%) completed the initial survey and 19 completed a repeat survey 2 weeks later for the test-retest comparison. Internal consistency coefficients for individual instruments ranged from 0.86-0.92. The piloted MOSS demonstrated good internal consistency (Cronbach's α=0.91; one-sided 95% CI ≥0.88) and test-retest reliability (r=0.86; p<0.0001). The MOSS also showed reasonable construct validity, correlating well with a single question of perceived occupational stress (ρ=0.46; p<0.001) over career satisfaction (ρ=-0.09; p>0.05). CONCLUSION: The individual, construct-specific measures included in this survey all demonstrated good internal consistency and test-retest reliability on examination. While the results are preliminary due to the small sample size, the MOSS psychometrically performed at a level equal to or better than other widely used and well-validated measures included in this survey.

The allocation of valenced concepts onto 3D space.

The valence-space metaphor research area investigates the metaphorical mapping of valenced concepts onto space. Research findings from this area indicate that positive, neutral, and negative concepts are associated with upward, midward, and downward locations, respectively, in the vertical plane. The same research area has also indicated that such concepts seem to have no preferential location on the horizontal plane. The approach-avoidance effect consists in decreasing the distance between positive stimuli and the body (i.e. approach) and increasing the distance between negative stimuli and the body (i.e. avoid). Thus, the valence-space metaphor accounts for the mapping of valenced concepts onto the vertical and horizontal planes, and the approach-avoidance effect accounts for the mapping of valenced concepts onto the "depth" plane. By using a cube conceived for the study of allocation of valenced concepts onto 3D space, we show in three studies that positive concepts are placed in upward locations and near the participants' body, negative concepts are placed in downward locations and far from the participants' body, and neutral concepts are placed in between these concepts in both planes.

Characteristics of Mexican and Mexican American adolescents in treatment for "cheese" heroin use.

Clinical and cultural characteristics of Hispanic adolescent heroin users are not well described. The current exploratory study was conducted to describe a sample of in-treatment Hispanic adolescents with opioid dependence, specifically, cheese heroin. Mexican and Mexican American adolescents with heroin dependence (N = 72) in three treatment programs were interviewed and completed self-report measures. Participants reported, on average, first using cheese heroin at age 13.5 years and daily use at age 14.2 years. The majority (74%) reported a previous overdose. Adolescents being raised by caregivers other than both biological parents, who used drugs with relatives, and whose immediate family members have documentation to be in the United States fared worse on several indicators of drug use severity and other risky behaviors. The self-reported brief time period from first use to daily use strongly suggests the need for early prevention efforts. Additional research is needed to add to these preliminary results and inform prevention efforts.

Fanconi Anemia, AML, and MDS.

OBJECTIVES: The Fanconi anemia (FA) genes are a family of at least 23 known genes that are spread across many chromosomes and participate in interstrand crosslink (ICLs) DNA repair. In this pathway, FA proteins are involved in sensing sites of ICLs, translocating repair enzymes from the cytoplasm to the nucleus, excising the area of damage, and facilitating repair of the fractured DNA. Mutations in these genes lead to Fanconi anemia, a syndrome characterized primarily by pancytopenia but with associated symptoms involving nearly every organ system; the majority of patients present with dermatological symptoms and growth deficits. Additionally, individuals with Fanconi anemia are known to be predisposed individuals to an increased risk of malignancies, particularly acute myeloid dystrophy and myelodysplastic syndrome, but also in the head, neck, esophagus, reproductive organs, brain, skin, liver, and kidneys. In fact, the cytogenetic aberrations seen in those with FA-associated AML differ from those in typical AML. In contrast, the cytogenetic changes seen in FA-associated MDS are similar to those in typical MDS.

ETV6::RUNX1-like Acute Lymphoblastic Leukemia.

OBJECTIVES: ETV6::RUNX1-like acute lymphoblastic leukemia (ALL) is a novel B-cell precursor leukemia subtype with similarities to ETV6::RUNX1 ALL without the presence of the ETV6-RUNX1 fusion gene. In this review, we survey the body of literature surrounding this recently categorized B-ALL type, including biomarkers, frequently associated mutations and prognosis of the disease. Identifying novel subcategories of B-ALL through high-throughput genetic analysis techniques allows for better guidance in management and more accurate prognosis.

Facial mimicry interference reduces working memory accuracy for facial emotion expressions.

Facial mimicry, the tendency to imitate facial expressions of other individuals, has been shown to play a critical role in the processing of emotion expressions. At the same time, there is evidence suggesting that its role might change when the cognitive demands of the situation increase. In such situations, understanding another person is dependent on working memory. However, whether facial mimicry influences working memory representations for facial emotion expressions is not fully understood. In the present study, we experimentally interfered with facial mimicry by using established behavioral procedures, and investigated how this interference influenced working memory recall for facial emotion expressions. Healthy, young adults (N = 36) performed an emotion expression n-back paradigm with two levels of working memory load, low (1-back) and high (2-back), and three levels of mimicry interference: high, low, and no interference. Results showed that, after controlling for block order and individual differences in the perceived valence and arousal of the stimuli, the high level of mimicry interference impaired accuracy when working memory load was low (1-back) but, unexpectedly, not when load was high (2-back). Working memory load had a detrimental effect on performance in all three mimicry conditions. We conclude that facial mimicry might support working memory for emotion expressions when task load is low, but that the supporting effect possibly is reduced when the task becomes more cognitively challenging.

FISH Still a Very Important Tool to Monitor Breast Cancer: Review of Recent Literature, Alternative Methods, and Proposed Techniques.

OBJECTIVES: Fluorescent in situ hybridization has been the definitive modality in testing for overexpression of the Human Epidermal Growth Factor Receptor 2 (HER2) for decades to guide the appropriate treatment for cancer patients. In more recent years innovation and new techniques have been developed to supplant or even replace FISH as a standard method for biomarker testing. Alternative testing methods such polymerase chain reaction (PCR), next-generation sequencing (NGS), and other in situ hybridization (ISH)-derived techniques such as chromogenic-ISH (CISH) have been shown in multiple publications to have high concordance with FISH in addition to advantages in economics, logistics and practicality to the point where CISH and derived methods appear to have eclipsed FISH as a testing method of choice after immunohistochemistry (IHC). This review assesses the status of FISH compared to other diagnostic techniques such as IHC, CISH, and less common and/or experimental methods. Also addressed are the updates to the guidelines from the American Society of Clinical Oncology (ASCO), College of American Pathologists (CAP), and National Comprehensive Cancer Network (NCCN) regarding FISH and IHC for HER2 testing with the updates reducing the number of equivocal diagnoses in the latest iteration. Though our findings show a constantly changing technological landscape, FISH remains an important primary tool to guide medical treatment and as a solid foundation to build upon for innovation in cancer research.

The Main Genetic-Molecular Aspects of Penile Cancer.

OBJECTIVES: Penile cancer, while relatively rare compared to other male malignancies, has seen an increased global incidence, with 36,068 new cases reported in 2020. This condition primarily affects regions with low human development indexes, notably India, China and Brazil. The mainstay of treatment is often partial or total penectomy, which has a profound impact on patients' emotional and social lives. Due to limited options for early diagnosis, non-surgical treatments, restricted healthcare funding and the negative consequences of mutilating surgeries, penile cancer is often considered a neglected disease. Penile cancer exhibits various histological types, but penile squamous cell carcinoma (SCC) is the most prevalent, accounting for 95% of cases worldwide. Multiple risk factors are associated with this condition, largely tied to lifestyle behaviors, such as promiscuous sexual behavior, zoophilia, poor hygiene, phototherapy, smoking and obesity. Human papillomavirus (HPV) infection is a significant etiological factor, particularly in squamous cell carcinomas. The prevalence of HPV in penile neoplasia varies widely, and its association with mortality remains uncertain.

A Case of a Patient with Therapy-related Core Binding Factor (CBF) Acute Myeloid Leukemia (CBF-AML).

OBJECTIVES: Identifying therapy-related AML (t-AML) of newly diagnosed acute leukemias is of great interest. Development of t-AML can occur after cytotoxic chemotherapy and/or radiation. We report a case of t-AML with CBFB::MYH11 fusion in a patient with a distant history of treated stage IIIB nodular sclerosing Hodgkin's lymphoma. We present the clinical course of the patient and the methods used to detect and monitor the rearrangement. Core binding factor AML (CBF-AML) after exposure to treatment is considered to be a good prognostic marker. The identification of these favorable AML subtypes such as CBF-AML highlights the importance of identifying genetic alterations, especially with increasing incidences of t-AML due to changes in choice of treatment and prognosis.

The American Society of Addiction Medicine Clinical Practice Guideline Development Methodology.

ABSTRACT: The American Society of Addiction Medicine (ASAM) has published clinical practice guidelines (CPGs) since 2015. As ASAM's CPG work continues to develop, it maintains an organizational priority to establish rigorous standards for the trustworthy production of these important documents. In keeping with ASAM's mission to define and promote evidence-based best practices in addiction prevention, treatment, and recovery, ASAM has rigorously updated its CPG methodology to be in line with evolving international standards. The CPG Methodology and Oversight Subcommittee was formed to establish and publish a methodology for the development of ASAM CPGs and to develop an ASAM CPG strategic plan. This article provides a focused overview of the ASAM CPG methodology.

JAK2 in Ph-like B-Acute Lymphoblastic Leukemia.

OBJECTIVES: The Janus Kinase 2 gene (JAK2) provides instructions for generating a protein that promotes the division and growth, or what is referred to as the proliferation, of cells. This generated protein relays signals in cells in order to promote cell growth, as well as help manage the count of white blood cells, red blood cells, and platelets that are generated within the bone marrow. Mutations and rearrangements of JAK2 are found in 3.5% of B-acute lymphoblastic leukemia (B-ALL) cases and in 18.9% of Down syndrome B-ALL patients, and are associated with a Ph-like ALL and a poor prognosis. However, there have been great challenges in understanding their role in this pathogenesis. In this review, we will discuss the most recent literature and trends associated with JAK2 mutations in patients with B-ALL.

The Key Role of the RPS14 Gene in Neoplasms and Solid Tumors.

OBJECTIVES: The ribosomal protein S14 (RPS14) gene located at 5q33 codes for a protein involved in ribosomal biogenesis. The RPS14 gene has a length of 5.9 kb of DNA comprising 5 exons and 4 introns. It is possible that RPS14 is involved in the formation of pre-RNA 18s, an intermediate RNA that serves for the formation of the 40S small subunit of the ribosome. RPS14 haploinsufficiency (HI) produces alterations in intermediate RNA levels (pre-RNA 30S/18SE/18S), which are found in del(5q) MDS. In addition, RPS14 haploinsufficiency results in the formation of the MDM2 (double minute mouse E3 ubiquitin ligase)-RP (ribosomal protein) complex that prevents the MDM2-p53 interaction, generating an accumulation of p53 levels. This accumulation produces cell cycle arrest, impaired DNA repair, senescence, and apoptosis. RPS14 haploinsufficiency has been seen in MDS. Altered expression levels of RPS14 have also been reported in glioma, colorectal cancer, hepatocellular carcinoma, breast cancer, renal cell carcinoma, and primary myelofibrosis.

Description and Evaluation of a Pilot Advanced Pharmacy Practice Experience in Addiction Medicine.

Objective. To assess the impact of a pilot advanced pharmacy practice experience (APPE) on fourth-year (P4) Doctor of Pharmacy (PharmD) students' knowledge and confidence related to substance use disorder, harm reduction, and co-occurring psychiatric conditions.Methods. Beginning in 2020, a 62-item assessment was developed and administered to P4 students at the beginning and end of the six-week APPE. The assessment tested knowledge in 10 content areas related to substance use disorder, harm reduction, and co-occurring disorders. Students also ranked their confidence in providing care related to each content area. The post-assessment included a free-text (open-ended) item to provide feedback on the APPE experience. Descriptive statistics and paired t tests were used to analyze the data.Results. Complete pre- and post-assessments were obtained from all participating students (N=7). The mean cumulative knowledge score increased from 55.2% to 81.5%, and the mean cumulative confidence score improved from 34.2% to 81.8%. Free-text responses garnered positive feedback from students, who indicated that the APPE allowed them to immerse themselves in all stages of the recovery process, gain confidence in presentation skills with patients, and solidify their passion for addiction medicine.Conclusion. A novel APPE in addiction medicine addressed a current gap in pharmacy education, earned positive evaluations from student pharmacists, increased student knowledge and confidence related to substance use disorder, harm reduction, and co-occurring disorders, and supported the development of new interprofessional collaborations. United States colleges of pharmacy that do not yet offer APPEs in this clinical domain should consider this model.

A B-ALL Pediatric Patient with a Cryptic IGH Rearrangement Within the Context of a Complex Karyotype.

OBJECTIVES: B-cell acute lymphoblastic leukemia (B-ALL) can afflict both adult and pediatric patients and is characterized by a build-up of B lymphoblasts. Here we present a case of a 25-year-old male patient with a history of B-ALL. Ninety percent of the bone marrow revealed pancytopenia with sheets of B lymphoblasts consistent with the diagnosis of B-ALL for acute pre-B lymphoblastic leukemia. The immunophenotype also presented predominant immature precursor B lymphoid cells positive for CD19, CD10, CD34, CD58, CD38, CD9, and TdT. Chromosome analysis of the bone marrow showed a complex karyotype described as 45~47,XY,i(8)(q10),der(10)add(10)(p11.1)add(10)(q23),-20,+1~2mar[cp3]/46,XY[36]. While IGH rearrangements were cryptic cytogenetically, DNA FISH analysis showed evidence of the IGH (14q32.2) gene rearrangement in 96.5% of the nuclei examined. These results were described as nuc ish(IGHx2)(5'IGH sep 3'IGHx1)[187/200],(5'IGH,3'IGH)x1~4(5'IGH con 3'IGHx0~2) [6/200]. The remaining probes were normal. Further studies using the MYC/IGH DC, DF probe from Abbott showed a gain of IGH signal in 7.5% of the nuclei examined: nuc ish(MYCx2,IGHx3)[15/200]. Metaphase FISH also showed that what appeared to be an isochromosome 8q was a derivative chromosome 8 defined as add(8)(p11.2) that contained a green IGH signal. In light of these results the karyotype was characterized as 45~47,XY,add(8)(p11.2),der(10)add(10)(p11.1)add(10)(q23),-20,+1~2mar[cp3].ish add(8) (p11.2) IgH+. IgH abnormalities are rare in B-ALL and are usually associated with a poor prognosis. However, at the present time our patient presented no evidence of persistent or residual disease and a cytogenetic response to the present therapy.

A Highly Complex Hyperdiploid Karyotype in a Patient with MDS: A Case Report and Review of the Literature.

OBJECTIVES: We present a case study of a 73-year-old female with a history of pancytopenia. The bone marrow core biopsy was suggestive of a myelodysplastic syndrome, unspecified (MDS-U). Chromosomal analysis of the bone marrow revealed an abnormal karyotype including gain of chromosomes 1, 4, 6, 8, 9, 19, and 20 in addition to loss of chromosomes 11, 13, 15, 16, 17, and 22. Also, additional material of unknown origin was found on 3q, 5p, 9p, 11p, 13p, 14p, and 15p; there were two copies of 19p, a deletion of 8q, and numerous unidentified rings and markers were present. This was characterized as: 75~77,XXX,+1,der(1;6)(p10;p10),add(3)(q27),+4,add(5)(p15.1),+6,+8,del(8)(q24.1),+add(9)(p24),-11,add (11) (p13),-13,add(13)(p10),add(14)(p11.2),-15,add(15)(p11.2), -16,-17,+19,add(19)(p13.3)x2,+20,-22, +0~4r,+4~10mar[cp11]/46,XX[8]. The cytogenetic analysis correlates with the concurrent FISH study which was positive for additional signals of EVI1(3q26.2), TAS2R1 (5p15.31), EGR1 (5q31.2), RELN (7q22), TES (7q31) RUNX1T1 (8q21.3), ABL1 (9q34), KMT2A (11q23), PML (15q24.1), CBFB (16q22), RARA (17q21), PTPRT (20q12), MYBL2 (20q13.12), RUNX1 (21q22.12) and BCR (22q11.2). Hyperdiploid karyotypes within the context of complex structural abnormalities are rare events usually associated with a poor prognosis in MDS.

Applications of isradipine in human addiction studies: A systematic literature review.

Given the personal and public health burden of addictive disorders, innovative approaches to treatment are sorely needed. This systematic review examined the use of the pharmacological agent isradipine in the context of potential applications for addiction treatment. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guided a comprehensive search of PubMed, Cochrane Library, and PsycINFO between the years 1985 to July 2022. Studies were included if isradipine was administered to adults with a current Diagnostic and Statistical Manual of Mental Disorders-5th edition diagnosis of a substance use disorder and/or to healthy volunteers alone and in conjunction with a substance (i.e, cocaine, methamphetamine, alcohol). A total of 16 studies with 252 participants were included in this review. Substantial variability was identified with study designs, isradipine dosages/dosing, and addictive substance of interest. Outcomes clustered in four categories: (a) cerebral blood flow (CBF), (b) hemodynamic effects, (c) subjective effects, and (d) cognitive effects. Isradipine was found to improve CBF in individuals with cocaine-induced hypoperfusion and in several studies was found to reduce parameters of blood pressure elevation after stimulant use. There were no significant findings on isradipine's effect on subjective reporting (i.e., craving, mood, drug affect) or cognition/attention. Given the limited number of studies identified in this review, there is insufficient data to draw clear conclusions. The direct effects of isradipine as a pharmacologic agent for addictive disorder treatment appear minimal, however, future work may benefit from examining the impact of isradipine as an augmentative agent within existing cue exposure paradigms for preventing cue-induced drug relapse. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

An Isochromosome 9q: A Rare Event in Pediatric B-ALL.

OBJECTIVES: B-cell acute lymphoblastic leukemia (B-ALL) is one of the most common leukemias affecting the pediatric population. It represents ~25% of cancer diagnoses among children. Specific genetic changes predict the prognosis in B-ALL with recurrent genetic changes. Here we present a case report of a 20-year-old male with B-ALL. The patient presented with acute onset worsening upper extremity pain with pallor, weight loss, dizziness, fatigue, and abnormal complete blood count (CBC). Conventional cytogenetics showed a karyotype of 46,XY,add(9)(q13),i(9)(q10)[19]. DNA FISH analysis performed on the bone marrow showed hemizygous deletion of the 9p21(CDKN2A) in 15.5% of the nuclei examined. The presence of an isochromosome 9q [i(9)(q10) is a rare event in pediatric B-ALL. An isochromosome 9q occurs in 0.6% of the patients studied in the literature. The significance of this abnormality in pediatric B-ALL is not clear. Profiling cases like this to understand the molecular mechanisms of rare chromosomal abnormalities and rare mutations in children with B-ALL could help us to better treat them.