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Abstract Background One of the major hurdles in clinical genetics is interpreting the clinical consequences associated with germline missense variants in humans. Recent significant advances have leveraged natural variation observed in large-scale human populations to uncover genes or genomic regions that show a depletion of natural variation, indicative of selection pressure. We refer to this as “genetic constraint”. Although existing genetic constraint metrics have been demonstrated to be successful in prioritising genes or genomic regions associated with diseases, their spatial resolution is limited in distinguishing pathogenic variants from benign variants within genes. Methods We aim to identify missense variants that are significantly depleted in the general human population. Given the size of currently available human populations with exome or genome sequencing data, it is not possible to directly detect depletion of individual missense variants, since the average expected number of observations of a variant at most positions is less than one. We instead focus on protein domains, grouping homologous variants with similar functional impacts to examine the depletion of natural variations within these comparable sets. To accomplish this, we develop the Homologous Missense Constraint (HMC) score. We utilise the Genome Aggregation Database (gnomAD) 125 K exome sequencing data and evaluate genetic constraint at quasi amino-acid resolution by combining signals across protein homologues. Results We identify one million possible missense variants under strong negative selection within protein domains. Though our approach annotates only protein domains, it nonetheless allows us to assess 22% of the exome confidently. It precisely distinguishes pathogenic variants from benign variants for both early-onset and adult-onset disorders. It outperforms existing constraint metrics and pathogenicity meta-predictors in prioritising de novo mutations from probands with developmental disorders (DD). It is also methodologically independent of these, adding power to predict variant pathogenicity when used in combination. We demonstrate utility for gene discovery by identifying seven genes newly significantly associated with DD that could act through an altered-function mechanism. Conclusions Grouping variants of comparable functional impacts is effective in evaluating their genetic constraint. HMC is a novel and accurate predictor of missense consequence for improved variant interpretation.

Unicompartmental and Total Knee Arthroplasty (UKA and TKA) are both established surgical options for the treatment of medial compartment osteoarthritis of the knee. However, the superiority of one over the other remains controversial. Our retrospective study aims to compare short-term functional outcomes in similar patients who underwent either TKA or UKA. Pre- and post-operative range of motion (ROM), the Oxford Knee Score (OKS), Knee Society Knee Score (KSKS), and Knee Society Function Score (KSFS) were used as outcome measures. Our sample included 57 patients, among which 27 underwent TKA and 30 underwent UKA, including one patient who underwent bilateral UKA. At 1 year, there were no differences in the OKS, KSKS, or KSFS scores between the two groups. There was a significantly better range of motion in patients who underwent UKA compared to TKA (122.9 ± 11.7 degrees vs 109.9 ± 13.9 degrees, p < 0.001). Functional outcomes following UKA and TKA were found to be similar. Hence, in view of its lower morbidity and shorter length of hospital stay, UKA may be considered over a TKA for the treatment of medial compartment osteoarthritis whenever deemed appropriate.

OBJECTIVES Functional disability is a common consequence of the ageing process and can lead to poor health outcomes due to the inability to perform activities of daily living (ADL) and instrumental activities of daily living (IADL) independently. However, the prevalence of functional disability among older adults in the Association of Southeast Asian Nations (ASEAN) region is poorly documented. This study aimed to assess the prevalence of functional disability and its impact on older adults in the ASEAN region. METHODS A systematic literature search was performed on 4 databases from inception until March 2021 to identify studies examining individuals aged 60 years and above reporting functional disabilities in the ASEAN region. Information on the prevalence and impact of functional disability was extracted, assessed for bias, summarised, and analysed using a random-effects meta-analysis. RESULTS Thirty-four studies with 59,944 participants were included. The pooled prevalence of ADL disability was 21.5% (95% confidence interval [CI], 16.2 to 27.3) and that of IADL disability was 46.8% (95% CI, 35.5 to 58.3). Subgroup analyses showed higher prevalence among those of advanced age and women. Adverse impacts included increased years of life with disability and poor health-related quality of life. CONCLUSIONS Nearly a quarter of the older adult population in the ASEAN region experience functional disability. These findings highlight the need for further research on the burden and impact of functional disability within this region to allow decision-makers to gauge the severity of the issue, develop policies to reduce the risk of developing functional disabilities, and foster healthy ageing.

Abstract Background International guidelines for variant interpretation in Mendelian disease set stringent criteria to report a variant as (likely) pathogenic, prioritising control of false-positive rate over test sensitivity and diagnostic yield. Genetic testing is also more likely informative in individuals with well-characterised variants from extensively studied European-ancestry populations. Inherited cardiomyopathies are relatively common Mendelian diseases that allow empirical calibration and assessment of this framework. Methods We compared rare variants in large hypertrophic cardiomyopathy (HCM) cohorts (up to 6179 cases) to reference populations to identify variant classes with high prior likelihoods of pathogenicity, as defined by etiological fraction (EF). We analysed the distribution of variants using a bespoke unsupervised clustering algorithm to identify gene regions in which variants are significantly clustered in cases. Results Analysis of variant distribution identified regions in which variants are significantly enriched in cases and variant location was a better discriminator of pathogenicity than generic computational functional prediction algorithms. Non-truncating variant classes with an EF ≥ 0.95 were identified in five established HCM genes. Applying this approach leads to an estimated 14–20% increase in cases with actionable HCM variants, i.e. variants classified as pathogenic/likely pathogenic that might be used for predictive testing in probands’ relatives. Conclusions When found in a patient confirmed to have disease, novel variants in some genes and regions are empirically shown to have a sufficiently high probability of pathogenicity to support a “likely pathogenic” classification, even without additional segregation or functional data. This could increase the yield of high confidence actionable variants, consistent with the framework and recommendations of current guidelines. The techniques outlined offer a consistent and unbiased approach to variant interpretation for Mendelian disease genetic testing. We propose adaptations to ACMG/AMP guidelines to incorporate such evidence in a quantitative and transparent manner.

Abstract Safely and efficiently controlling gene expression is a long-standing goal of biomedical research, and CRISPR/Cas system can be harnessed to create powerful tools for epigenetic editing. Adeno-associated-viruses (AAVs) represent the delivery vehicle of choice for therapeutic platform. However, their small packaging capacity isn’t suitable for large constructs including most CRISPR/dCas9-effector vectors. Thus, AAV-based CRISPR/Cas systems have been delivered via two separate viral vectors. Here we develop a compact CRISPR/dCas9-based repressor system packaged in AAV as a single optimized vector. The system comprises the small Staphylococcus aureus (Sa)dCas9 and an engineered repressor molecule, a fusion of MeCP2’s transcription repression domain (TRD) and KRAB. The dSaCas9-KRAB-MeCP2(TRD) vector platform repressed robustly and sustainably the expression of multiple genes-of-interest, in vitro and in vivo, including ApoE, the strongest genetic risk factor for late onset Alzheimer’s disease (LOAD). Our platform broadens the CRISPR/dCas9 toolset available for transcriptional manipulation of gene expression in research and therapeutic settings.

Abstract Background Cannabis was legalised for medical purposes in 2016. Uptake was initially slow, but since 2019 there has been a large increase in the number of Australians who have been prescribed cannabis for medical reasons. Yet a significant number of consumers continue to treat their medical conditions via illicitly-sourced cannabis. Little is known about how these two groups of medical cannabis consumers differ. Methods The anonymous Cannabis-As-Medicine Survey 2022–2023 (CAMS-22) was available for completion online from December 2022 to April 2023 to adult Australians who had used cannabis to treat a medical condition in the previous year. Recruitment occurred through social media, consumer forums, and medical practices. Questions included demographic characteristics, patterns of cannabis use, conditions treated, and self-rated effectiveness. Results Of the 3323 respondents included in these analyses, 2352 (73%) mainly used prescribed medical cannabis, 871 (27%) mainly used illicit. Prescribed users were significantly more likely than illicit users to have had their health condition diagnosed (OR = 1.7, 95% CI 1.3, 2.2), to consume their cannabis via oral (OR = 1.9; CI 1.5, 2.4) or vaporised (OR = 5.2; CI 4.0, 6.8) routes, and to be sure of the composition of their medical cannabis (OR = 25.0; CI 16.7, 50.0). Prescribed users were significantly less likely to have used cannabis non-medically before medical use (OR = 0.6, CI 0.5, 0.7), consume cannabis via smoked routes (OR = 0.2, CI 0.1, 0.2), and to report any side effects (OR = 0.1; CI 0.1, 0.2). The most common conditions among both prescribed and illicit users were pain (37%), mental health (36%), and sleep (15%) conditions. Prescribed users were significantly more likely to use cannabis to mainly treat a pain (OR = 1.3; CI 1.1, 1.5) or sleep condition (OR = 1.4; CI 1.1, 1.7) and less likely to treat a mental health condition (OR = 0.8; CI 0.7, 0.9). There were no between-group differences in effectiveness with 97% saying medical cannabis had improved their symptoms. Conclusions From a harm-reduction perspective there is much to recommend prescribed medical cannabis; it has fewer side-effects than illicit, is used more safely (oral or vaporised versus smoked routes), gives consumers greater certainty regarding the composition and quality of their medicine, and does not risk exposure to the criminal justice system. Of concern, however, is the apparent willingness of prescribers to prescribe for indications for which there is limited evidence of efficacy, such as mental health and sleep conditions.

Brentuximab vedotin (BV) monotherapy (BV-M) and combination (BV-C) therapies are safe and effective for classical Hodgkin lymphoma (cHL) and CD30-expressing peripheral T-cell lymphomas (PTCLs). Although the sample sizes have been small (12–29 patients), in clinical studies, response rates of 53–88% have been reported for BV retreatment in patients with an initial BV response. We evaluated the real-world characteristics and treatment patterns of cHL/PTCL patients who received BV and were retreated in the United States. Symphony Health Patient Claims (11/2013–1/2022) were retrospectively analyzed to identify cHL/PTCL patients treated with BV and retreated with BV-M, BV-C, or non-BV therapy. Patient characteristics were described by retreatment, and predictors of BV-M retreatment were identified. Among the cHL and PTCL patients treated with BV (n = 6442 and 2472, respectively), 13% and 12%, respectively, were retreated with BV; the median times from initial BV to BV-M retreatment were 5 and 7 months, respectively; and the numbers of BV-M retreatment doses were 4 and 5, respectively. Among cHL patients, the predictors of BV-M retreatment were age (18–39 vs. ≥60 years), sex (women vs. men), and previous stem cell transplantation (yes vs. no). Among PTCL patients, the only predictor of BV-M retreatment was systemic anaplastic large-cell lymphoma subtype (yes vs. no). Real-world data support clinical study results suggesting earlier BV treatment be considered, as BV retreatment may be an option.

Introduction We describe the identification and management of general population screen-detected type 1 diabetes (T1D) and share learnings for best practice.Research design and methods Children diagnosed with T1D through a general population screening initiative, the EarLy Surveillance for Autoimmune diabetes (ELSA) study, were reviewed and described.Parents provided written, informed consent for inclusion in the case series.Results 14 children with insulin requiring (stage 3) T1D are described. These cases offer unique insights into the features of screen-detected T1D. T1D is identified sooner through screening programs, characterized by absent/short symptom duration, median presenting glycated hemoglobin 6.6% (49 mmol/mol) and insulin requirements

Introduction Supervised injectable opioid treatment (SIOT) is an evidence-based intervention targeting opioid-dependent people for whom existing treatments have been ineffective. This project will primarily assess the feasibility and the acceptability of time-limited SIOT using injectable hydromorphone delivered in an existing Australian public opioid treatment programme, with secondary outcomes of safety, cost, changes in drug use and other health outcomes. If feasible, the goal is to scale up the intervention to be more widely available in Australia.Methods and analysis Between 20 and 30 participants will be offered two times per day hydromorphone to inject under direct observation, in addition to their current opioid agonist treatment (OAT), for up to 2 years. At the end of 2 years of supervised hydromorphone treatment, participants will be continued on standard OAT only. Informed consent will be obtained from all participants included in the study. This is a single-site, uncontrolled, open-label study where quantitative and qualitative interview data will be collected at baseline, 12 months and lastly at 3 months following their final hydromorphone dose. The main outcome measures are feasibility, as assessed by recruitment, retention and participation in treatment, and acceptability to participants, clinic staff and other stakeholders assessed by qualitative interviews. Secondary outcome measures of safety, as assessed by adverse events, and cost will also be assessed, as well as a range of other drug and health outcomes.Ethics and dissemination This study received ethical approval from the St Vincent’s Hospital Human Research Ethics Committee (2019/ETH00418). This will be the first study of time-limited SIOT in the Australian setting. All results will be submitted to peer-reviewed journals, scientific conferences and local practice meetings. A preliminary report on outcomes will also be presented to local health policy makers. A consumer and community forum will also be held to feedback results to a broader audience.Trial registration number ACTRN12621001729819.

Abstract The underlying neurobiological mechanisms of cannabidiol’s (CBD) management of alcohol use disorder (AUD) remains elusive. Aim We conducted a systematic review of neuroimaging literature investigating the effects of CBD on the brain in healthy participants. We then theorise the potential neurobiological mechanisms by which CBD may ameliorate various symptoms of AUD. Methods This review was conducted according to the PRISMA guidelines. Terms relating to CBD and neuroimaging were used to search original clinical research published in peer-reviewed journals. Results Of 767 studies identified by our search strategy, 16 studies satisfied our eligibility criteria. The results suggest that CBD modulates γ-Aminobutyric acid and glutamate signaling in the basal ganglia and dorso-medial prefrontal cortex. Furthermore, CBD regulates activity in regions associated with mesocorticolimbic reward pathways; salience, limbic and fronto-striatal networks which are implicated in reward anticipation; emotion regulation; salience processing; and executive functioning. Conclusion CBD appears to modulate neurotransmitter systems and functional connections in brain regions implicated in AUD, suggesting CBD may be used to manage AUD symptomatology.

Abstract Background Cannabis use disorder (CUD) is increasingly common and contributes to a range of health and social problems. Cannabidiol (CBD) is a non-intoxicating cannabinoid recognised for its anticonvulsant, anxiolytic and antipsychotic effects with no habit-forming qualities. Results from a Phase IIa randomised clinical trial suggest that treatment with CBD for four weeks reduced non-prescribed cannabis use in people with CUD. This study examines the efficacy, safety and quality of life of longer-term CBD treatment for patients with moderate-to-severe CUD. Methods/Design A phase III multi-site, randomised, double-blinded, placebo controlled parallel design of a 12-week course of CBD to placebo, with follow-up at 24 weeks after enrolment. Two hundred and fifty adults with moderate-to-severe CUD (target 20% Aboriginal), with no significant medical, psychiatric or other substance use disorders from seven drug and alcohol clinics across NSW and VIC, Australia will be enrolled. Participants will be administered a daily dose of either 4 mL (100 mg/mL) of CBD or a placebo dispensed every 3-weeks. All participants will receive four-sessions of Cognitive Behavioural Therapy (CBT) based counselling. Primary endpoints are self-reported cannabis use days and analysis of cannabis metabolites in urine. Secondary endpoints include severity of CUD, withdrawal severity, cravings, quantity of use, motivation to stop and abstinence, medication safety, quality of life, physical/mental health, cognitive functioning, and patient treatment satisfaction. Qualitative research interviews will be conducted with Aboriginal participants to explore their perspectives on treatment. Discussion Current psychosocial and behavioural treatments for CUD indicate that over 80% of patients relapse within 1–6 months of treatment. Pharmacological treatments are highly effective with other substance use disorders but there are no approved pharmacological treatments for CUD. CBD is a promising candidate for CUD treatment due to its potential efficacy for this indication and excellent safety profile. The anxiolytic, antipsychotic and neuroprotective effects of CBD may have added benefits by reducing many of the mental health and cognitive impairments reported in people with regular cannabis use. Trial registration Australian and New Zealand Clinical Trial Registry: ACTRN12623000526673 (Registered 19 May 2023).

Abstract Background In April 2020, in response to the COVID-19 public health emergency, South Eastern Sydney Local Health District (SESLHD) Drug and Alcohol services modified their delivery of opioid dependency treatment (ODT) to reduce spread of COVID-19 and maintain continuity of care by increasing use of takeaway doses (TADs), transferring clients to local community pharmacies for dosing and encouraging the use of long-acting depot buprenorphine (LADB) which enabled once a month dosing. Methods This study was a retrospective longitudinal case–control study conducted from August 1st, to November 30th, 2021. Eligible clients were those admitted for treatment with SESLHD ODT Services prior to August 1st,2021 and who remained in treatment beyond November 30th, 2021. COVID-19 diagnoses were determined by a COVID-19 PCR and extracted from the electronic Medical Records (eMR) Discern Reporting Portal. Demographic, clinical and dosing related data were collected from eMR and the Australian Immunisation Register (AIR). Results Clients attending SESLHD ODT services had significantly greater odds of acquiring COVID-19 than the NSW adult population at large (OR: 13.63, 95%CI: 9.64,18.88). Additionally, amongst SESLHD ODT clients, being of Aboriginal and Torres Strait Islander origin was associated with greater odds of acquiring COVID-19 (OR = 2.18, CI: 1.05,4.53); whilst being employed (OR = 0.06, CI:0.01,0.46), receiving doses at pharmacy (OR = 0.43, CI: 0.21,0.89), and being vaccinated (OR = 0.12, CI: 0.06,0.26) were associated with lower odds. Every additional day of attendance required for dosing was associated with a 5% increase in odds of acquiring COVID-19 (OR = 1.05, CI: 1.02,1.08). Conclusions Clients attending SESLHD ODT services are significantly more likely to acquire COVID-19 than the NSW population at large. Promoting vaccination uptake, transferring clients to pharmacy, and reducing the frequency of dosing (by use of takeaway doses or long-acting depot buprenorphine) are all potential methods to reduce this risk.

BackgroundThe primary objective is to evaluate the safety and effectiveness of Stryker second generation Target® Nano Coils in the treatment of ruptured and unruptured small (

Summary: Background: Endogenous retroelements (EREs), including human endogenous retroviruses (HERVs) and long interspersed nuclear elements (LINEs), comprise almost half of the human genome. Our previous studies of the interferome in the gut suggest potential mechanisms regarding how IFNb may drive HIV-1 gut pathogenesis. As ERE activity is suggested to partake in type 1 immune responses and is incredibly sensitive to viral infections, we sought to elucidate underlying interactions between ERE expression and gut dynamics in people living with HIV-1 (PLWH). Methods: ERE expression profiles from bulk RNA sequencing of colon biopsies and PBMC were compared between a cohort of PLWH not on antiretroviral therapy (ART) and uninfected controls. Findings: 59 EREs were differentially expressed in the colon of PLWH when compared to uninfected controls (padj

Abstract Background Macrophage activation syndrome is a rare disorder leading to unregulated immune activity manifesting with nonspecific constitutional symptoms, laboratory abnormalities, and multiorgan involvement. We report the case of a patient who presented with acute hepatitis secondary to macrophage activation syndrome diagnosed by liver biopsy and successfully treated with intravenous immune globulin, anakinra, and rituximab. Case presentation A 42-year-old Laotian woman with adult-onset immunodeficiency with anti-interferon gamma antibodies presented with a fever, headache, generalized myalgia, dark urine, and reduced appetite in the setting of family members at home with similar symptoms. Her laboratory workup was notable for evidence of acute hepatitis without acute liver failure. After an unrevealing comprehensive infectious and noninvasive rheumatologic workup was completed, a liver biopsy was performed ultimately revealing the diagnosis of macrophage activation syndrome. She was successfully treated with intravenous immune globulin, anakinra, and rituximab. Conclusion This case highlights the importance of maintaining macrophage activation syndrome on the differential of a patient with acute hepatitis of unknown etiology in the correct clinical context and the value of a liver biopsy in making a diagnosis when noninvasive testing is unrevealing.

Patient-reported outcome measures (PROs) are increasingly used in clinical assessment. Research on how patient support systems contribute to physician understanding of patient condition is limited. Thus, insights from significant others may provide value, especially when concerns exist regarding patient response validity. Patients recruited from the pre-operative environment undergoing orthopaedic hand procedures responded to PROMIS-Pain Interference (PI), PROMIS-Upper Extremity (UE), PROMIS-Depression (D), and QuickDASH. They then selected a significant other (SO) to do the same. Patients and SOs were also asked to complete the West Haven-Yale Multidimensional Pain Inventory (WHYMPI) as a measure of support-related responses. Patient and SO responses were compared, and support-related responses were added in subsequent analyses to examine their effect on SO PRO assessment.

mRNA vaccine technologies introduced following the SARS-CoV-2 pandemic have highlighted the need to better understand the interaction of adjuvants and the early innate immune response. Type I interferon (IFN-I) is an integral part of this early innate response that primes several components of the adaptive immune response. Women are widely reported to respond better than men to tri- and quadrivalent influenza vaccines. Plasmacytoid dendritic cells (pDCs) are the primary cell type responsible for IFN-I production, and female pDCs produce more IFN-I than male pDCs since the upstream pattern recognition receptor Toll-like receptor 7 (TLR7) is encoded by X chromosome and is biallelically expressed by up to 30% of female immune cells. Additionally, the TLR7 promoter contains several putative androgen response elements, and androgens have been reported to suppress pDC IFN-I in vitro. Unexpectedly, therefore, we recently observed that male adolescents mount stronger antibody responses to the Pfizer BNT162b2 mRNA vaccine than female adolescents after controlling for natural SARS-CoV-2 infection. We here examined pDC behaviour in this same cohort to determine the impact of IFN-I on anti-spike and anti-receptor-binding domain IgG titres to BNT162b2. Through flow cytometry and least absolute shrinkage and selection operator (LASSO) modelling, we determined that serum-free testosterone was associated with reduced pDC IFN-I, but contrary to the well-described immunosuppressive role for androgens, the most bioactive androgen dihydrotestosterone was associated with increased IgG titres to BNT162b2. Also unexpectedly, we observed that co-vaccination with live attenuated influenza vaccine boosted the magnitude of IgG responses to BNT162b2. Together, these data support a model where systemic IFN-I increases vaccine-mediated immune responses, yet for vaccines with intracellular stages, modulation of the local IFN-I response may alter antigen longevity and consequently improve vaccine-driven immunity.

Abstract Road safety is an important concern amidst expanding worldwide access to legal cannabis. The present study reports on the driving-related subsection of the Cannabis as Medicine Survey 2020 (CAMS-20) which surveyed driving-related behaviors, attitudes, and perceptions among Australian medical cannabis (MC) users. Of the 1063 respondents who reported driving a motor vehicle in the past 12 months, 28% (297/1063) reported driving under the influence of cannabis (DUIC). Overall, 49–56% of respondents said they typically drive within 6 h of MC use, depending on the route of administration (oral or inhaled). Non-medical cannabis (NMC) was perceived to be more impairing for driving than MC. Binary logistic regression revealed associations between likelihood of DUIC and (1) inhaled routes of cannabis administration, (2) THC-dominant products, (3) illicit rather than prescribed use, (4) believing NMC does not impair driving, and (5) not being deterred by roadside drug testing. Overall, these findings suggest there is a relatively low perception of driving-related risk among MC users. Targeted education programs may be needed to highlight the potential risks associated with DUIC, and further research is needed to determine whether driving performance is differentially affected by MC and NMC.

Existing primary evidence comparing fibular intramedullary fixation (IMF) with traditional plate fixation (PF) for the treatment of distal fibular fractures remains limited by modest sample sizes. Using a large national database, this study aims to compare use rates, fracture patterns, patient characteristics, time to surgery, complication rates, and cost between fibular IMF and PF within the United States. Adults treated with fibular IMF or PF between October 2015 and October 2021 were identified within the PearlDiver Database. The ratio of IMF-treated to PF-treated patients was tracked temporally to compare use rates. Fracture patterns were determined using fracture diagnoses within one-month preceding surgery. Further comparisons of IMF- and PF-treated groups only included patients with at least 12 months of follow-up, and patients with upper tibia or tibia shaft fractures were excluded. An analysis of cohorts matched at a 1 : 4 (IMF: PF) ratio to control for risk factors was performed to compare time to surgery, complication rates (infection, nonunion, malunion, revision, hardware removal, pulmonary embolism, and deep vein thrombosis), and cost. 39329 patients (2294 IMF and 37035 PF) were identified. IMF use trended upwards relative to PF use over time. Tibia and fibula shaft fractures were the most common injuries in IMF patients versus bimalleolar and trimalleolar fractures in PF patients. A higher proportion of IMF patients had open fractures. IMF patients were younger, with higher mean ECI, fewer female patients, and higher rates of CKD. Percutaneous approaches were more common among IMF patients. There were no significant differences in time to surgery or complication rates. IMF was less costly. The popularity of IMF trended upwards across the study period. IMF was used more commonly in injuries involving higher energy trauma and soft tissue disruption. Overall, IMF patients were younger with more comorbidities. When used in similar populations, IMF appears to be a cost-effective alternative to PF.

This paper provides a rationale and convention for discussing the true limits and interpretation of data collected using unidimensional, summated, Likert-type, and attitudinal scales used in research investigating human behavior, sociology, education, psychology, and other related fields of study. All vague quantifiers must be described in methods and findings. The true limits of the scale and of each vague quantifier should be described. This information should be placed in the methods section. A five-point summated scale, for example, can be interpreted as follows: Strongly Agree = 5 - 4.51, Agree = 4.5 - 3.51, Neither Agree nor Disagree = 3.5 - 2.51, Disagree = 2.5 - 1.51, Strongly Disagree = 1.5 - 1. This paper also provides a rationale and convention for the use of nonstandardized effect size (ES) estimates to describe the magnitude and strength of the effect. This is accomplished by subtracting one summated M from another summated M and interpreted using the following convention: Small (ES = .19 and lower); Medium (ES = .20 - .49); and Large (ES = .50 and higher). The rationale for this is based on the intuitiveness of the measure, true limits of the scale, and scale intervals.