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Threshold Assessment Grid (TAG): the development of a valid and brief scale to assess the severity of mental illness.

BACKGROUND: Lack of consensus about the meaning of severe mental illness makes it difficult to prioritise the severely mentally ill for specialist mental health care. The goal of this study was to develop a valid and brief assessment of severity of mental illness. METHOD: Six search workshops (n = 57) using consensus techniques developed a draft assessment acceptable to users, carers, practitioners and policy makers. A two-round Delphi consultation (n = 58) was held to identify consensus on this instrument. RESULTS: Search workshops agreed seven domains relevant to identifying the severely mentally ill: intentional and unintentional self-harm, risk from and to others, and survival, psychological, and social needs and disabilities. The Delphi consultation indicated at least agreement with all aspects in both rounds. CONCLUSIONS: The Threshold Assessment Grid (TAG) is a brief method of identifying the severely mentally ill, which has adequate face, concurrent, construct and content validity.

Delphi Technique↗

Development of core competencies for an international training programme in intensive care medicine.

OBJECTIVE: The aim of this study was to define the core (minimum) competencies required of a specialist in adult intensive care medicine (ICM). This is the second phase of a 3-year project to develop an internationally acceptable competency-based training programme in ICM for Europe (CoBaTrICE). METHODOLOGY: Consensus techniques (modified Delphi and nominal group) were used to enable interested stakeholders (health care professionals, educators, patients and their relatives) to identify and prioritise core competencies. Online and postal surveys were used to generate ideas. A nominal group of 12 clinicians met in plenary session to rate the importance of the competence statements constructed from these suggestions. All materials were presented online for a second round Delphi prior to iterative editorial review. RESULTS: The initial surveys generated over 5,250 suggestions for competencies from 57 countries. Preliminary editing permitted us to encapsulate these suggestions within 164 competence stems and 5 behavioural themes. For each of these items the nominal group selected the minimum level of expertise required of a safe practitioner at the end of their specialist training, before rating them for importance. Individuals and groups from 29 countries commented on the nominal group output; this informed the editorial review. These combined processes resulted in 102 competence statements, divided into 12 domains. CONCLUSION: Using consensus techniques we have generated core competencies which are internationally applicable but still able to accommodate local requirements. This provides the foundation upon which an international competency based training programme for intensive care medicine can be built.

Clinical Competence↗

Research priorities in critical care medicine in the UK.

OBJECTIVES: To establish priorities for research in critical care medicine in the UK using survey and nominal group (NG) techniques. DESIGN: The senior doctor and nurse from 325 intensive care units (ICUs) in the UK were invited to contribute up to ten research questions relevant to intensive care organisation, practice or outcomes. These were then ranked twice using a Likert scale by a panel (nominal group) consisting of ten doctors (two trainees) and two nurses from university teaching and district general (community) hospitals. The first ratings were performed privately, and the second after group discussion. Thirty questions, ten each with strong, moderate or weak support, were then returned for rating by the originating ICU staff and the results compared with those of the NG. RESULTS: One hundred eighty-five respondents (35.6 % university teaching, 62.1% district general, 2.3 % not stated) provided 811 questions of which 722 were research hypotheses. The most frequently identified topics were the evaluation of high dependency care, ICU characteristics, treatments for acute lung injury and acute renal failure, nurse:patient ratios, pulmonary artery catheterisation, aspects of medical and nursing practice, protocol evaluation, and interhospital transfers. These were condensed into 100 topics for consideration by the NG. Discussion and re-rating by the group resulted in strong support being offered for 37 topics, moderate support for 48, and weak support for 21. Following circulation of ten questions from each category, nine questions achieved strong support from both ICU staff and the NG. These were the effect on outcomes from critical illness of early intervention, high dependency care, nurse:patient ratios, interhospital transfers, early enteral feeding, optimisation of perioperative care, hospital type, regionalisation of paediatric intensive care and the use of pulmonary artery catheters. The absence of any questions relating to interventions targetting mediators of the immuno-inflammatory response could be a consequence of the failure of recent studies in sepsis to demonstrate benefits in outcome. CONCLUSIONS: The intensive care community in the UK appears to prioritise research into organisational aspects of clinical practice and practical aspects of organ-system support. Health services research and the biological sciences need to develop collaborative methods for evaluating interventions and outcomes.

Attitude of Health Personnel↗

Quality over quantity: biopsy-anchored CT radiogenomics models outperform all-lesion training in a multi-tumour cohort despite a smaller sample size.

OBJECTIVE: Radiogenomics aims to non-invasively predict tumour genotypes from imaging, but most studies assume molecular homogeneity by assigning a single biopsy-derived label to all lesions within a patient. This approach risks substantial label noise given well-documented interlesional heterogeneity. We investigated whether anchoring training to biopsy-confirmed lesions improves radiogenomic model performance and generalisability. MATERIALS AND METHODS: We retrospectively analysed 1646 patients (11473 segmented lesions) with contrast-enhanced CT and EGFR mutation status from next-generation sequencing at the Netherlands Cancer Institute, alongside an external NSCLC radiogenomics cohort (n = 158). All visible lesions were segmented, and the exact biopsy site was matched to its segmentation. Radiomic features were extracted, and machine learning models were trained with three lesion selection strategies: all lesions, non-biopsied lesions only, and biopsy-confirmed lesions only. To disentangle label quality from sample size, we created size-matched variants (one lesion per patient) for all-lesion and non-biopsied strategies. RESULTS: All models achieved significant discrimination of EGFR status on internal validation (AUC = 0.62-0.68). However, performance of the all-lesion and non-biopsied models declined on external validation (AUC = 0.55-0.63), while the biopsy-anchored model maintained stable performance (AUC = 0.62), despite having only 1/10th of the training sample size. When training sets were size-matched, the biopsy-anchored approach significantly outperformed a model trained on all available lesions on external validation (p = 0.037). CONCLUSIONS: Radiogenomic models trained on biopsy-confirmed lesions outperform conventional all-lesion strategies in external validation, despite using an order of magnitude fewer samples. Prioritising lesion-level label fidelity can mitigate heterogeneity-driven noise, enhancing robustness and clinical translation of imaging-based genomic prediction. KEY POINTS: Question Does assigning biopsy-derived molecular labels to all lesions introduce heterogeneity-driven label noise that reduces the generalisability of radiogenomic models? Findings Models trained exclusively on biopsy-confirmed lesions demonstrated superior external generalisability compared with all-lesion approaches, despite being trained on substantially fewer samples. Clinical relevance Biopsy-anchored radiogenomics improves the reliability of non-invasive mutation prediction by accounting for tumour heterogeneity, potentially supporting clinical decision-making when tissue sampling is limited or molecular results are discordant across lesions.

Humans↗

A giant novel gene undergoing extensive alternative splicing is severed by a Cornelia de Lange-associated translocation breakpoint at 3q26.3.

Cornelia de Lange syndrome (CdLS) is a rare developmental malformation syndrome characterised by mental handicap, growth retardation, distinctive facial features and limb reduction defects. The vast majority of CdLS cases are sporadic. We carried out a high density bacterial artificial chromosome (BAC) microarray comparative genome hybridisation screen but no evidence was found for a consistent pattern of microdeletion/microduplication. As an alternative, we focused on identifying chromosomal regions spanning associated translocation breakpoints. We prioritised the distal 3q region because of the occurrence, in a classical CdLS patient, of a de novo balanced translocation with a breakpoint at 3q26.3 and of reports of phenotypic overlap between cases of mild CdLS and individuals trisomic for the 3q26-q27 region. We show that the 3q26.3 breakpoint severs a previously uncharacterised giant gene, NAALADL2, containing at least 32 exons spanning 1.37 Mb. Northern blot analysis identified up to six different transcripts in the 1-10 kb range with strongest expression in kidney and placenta; embryonic expression was largely confined to duodenal and stomach endoderm, mesonephros, metanephros and pancreas. Transcript analysis identified extensive alternative splicing leading to multiple 5' and 3' untranslated regions and variable coding sequences. Multiple protein isoforms were defined by different N-terminal regions (with at least four alternative initiating methionine codons), and by differential protein truncation/use of alternative C-terminal sequences attributable to alternative splicing/polyadenylation. Outside the N-terminal regions, the predicted proteins showed significant homology to N-acetylated alpha-linked acidic dipeptidase and transferrin receptors. Mutation screening of NAALADL2 in a panel of CdLS patient DNA samples failed to identify patient-specific mutations. We discuss the possibility that the 3q26.3 translocation could nevertheless contribute to pathogenesis.

Alternative Splicing↗

Transparent criteria for specialist level adolescent psychiatric care.

BACKGROUND: Rising health care costs and long waiting lists pose a challenge to public specialist level health services. In Finland, the Ministry of Social Affairs and Health required all medical specialities to create a priority-rating tool for elective patients, preferably giving a numerical rating ranging 0-100, with 50 as an entry threshold. OBJECTIVE: To create and test the psychometric properties of a point-count measure for prioritising entry to public specialist level adolescent psychiatric services. METHOD: Around 710 referred adolescents were given ratings on 17 items focusing on symptom severity, problem behaviours, functioning, progress of adolescent development and prognosis. The structured ratings were compared to an overall assessment of need for treatment on a VAS scale. In order to ensure that the tool was not inappropriately sensitive to confounding by non-disturbance related factors, the associations between the structured priority rating and sex, age, referring agent, study site and diagnosis were analysed. RESULTS: Of the 17 items, 15 were included in the final priority-rating tool. The requirement than threshold score for entry to services being set at 50 points necessitated scoring factors rather than individual items. Four blocks of items were formed: symptoms and risks; impaired functioning; other relevant issues, and prognosis without specialist level treatment. Most of the referred adolescents scored over the threshold of 50. When diagnosis was controlled for, scoring over 50 was largely independent of age, sex, referring agent or study site. CONCLUSION: The structured priority ratings corresponded well with clinical global rating of need for care. The tool was not inappropriately sensitive to age, sex, referring agent or study site. In the future, follow-up studies will be needed to evaluate the predictive value of priority ratings.

Adolescent↗

Primate errors in transitive 'inference': a two-tier learning model.

Transitive performance (TP) is a learning-based behaviour exhibited by a wide range of species, where if a subject has been taught to prefer A when presented with the pair AB but to prefer B when presented with the pair BC, then the subject will also prefer A when presented with the novel pair AC. Most explanations of TP assume that subjects recognize and learn an underlying sequence from observing the training pairs. However, data from squirrel monkeys (Saimiri sciureus) and young children contradict this, showing that when three different items (a triad) are drawn from the sequence, subjects' performance degrades systematically (McGonigle and Chalmers, Nature 267:694-696, 1977; Chalmers and McGonigle, Journal of Experimental Child Psychology 37:355-377, 1984; Harris and McGonigle, The Quarterly Journal of Experimental Psychology 47B:319-348, 1994). We present here the two-tier model, the first learning model of TP which accounts for this systematic performance degradation. Our model assumes primate TP is based on a general-purpose task learning system rather than a special-purpose sequence-learning system. It supports the hypothesis of Heckers et al. (Hippocampus 14:153-162, 2004) that TP is an expression of two separate general learning elements: one for associating actions and contexts, another for prioritising associations when more than one context is present. The two-tier model also provides explanations for why phased training is important for helping subjects learn the initial training pairs and why some subjects fail to do so. It also supports the Harris and McGonigle (The Quarterly Journal of Experimental Psychology 47B:319-348, 1994) explanation of why, once the training pairs have been acquired, subjects perform transitive choice automatically on two-item diads, but not when exposed to triads from the same sequence.

Animals↗

Systematic review and meta-analysis of circulating microRNAs in dengue infection: biomarkers, pathogenesis, and clinical implications.

Dengue infection is a mosquito-borne disease that can cause mild illness or severe haemorrhagic fever. Predictive biomarkers for severe cases, especially those with bleeding manifestations or plasma leakage, are currently lacking. This systematic review and meta-analysis synthesises findings from studies on circulating miRNAs in dengue infection, sourced from PubMed, Scopus, Science Direct, and Web of Science, with quality assessed by the Newcastle-Ottawa Scale (PROSPERO: CRD42024521685). Quantitative meta-analyses were conducted using RStudio to evaluate diagnostic Area Under the Curve (AUC) metrics across five eligible studies and Standardised Mean Differences (SMD) for differential miRNA expression. Key miRNAs, such as miR-146a, miR-150, miR-378, miR-21-5p, and miR-1246, were found to regulate immune responses, inflammation, and viral replication. Meta-analysis demonstrated high overall diagnostic accuracy for circulating miRNAs, with individual reported AUC values ranging from 0.79 to 1.00; however, substantial statistical heterogeneity was observed across pooled metrics (I-squared exceeding 89%). SMD analysis highlighted significant upregulation of acute inflammatory drivers, including miR-21-5p (SMD = 4.67) and miR-450b-5p (SMD = 6.76), alongside marked downregulation of endothelial-protective markers such as miR-126-3p (SMD = -1.31). Rather than viewing dysregulated microRNAs as a uniform class of clinical tools, this review highlights that candidate microRNAs span distinct translational tiers. Recognising these validation levels alongside pre-analytical and biological heterogeneity is essential for prioritising the most viable microRNA candidates for future prospective clinical translation and targeted therapies in dengue management.

Humans↗

A machine learning approach to identify key epigenetic transcripts for ageing research in human blood (Epitage).

DNA methylation is an established biomarker of human ageing and is used by a variety of tools to identify meaningful epigenetic signals. We investigated whether analysing CpGs grouped by transcript as functional units could generate a ranked list of transcripts most correlated with age that might otherwise be overlooked in genome-wide CpG-based studies. Here we present Epitage ( https://github.com/a00s/epitage ), a continuously updated ranked list of transcripts built from the GSE87571 dataset (714 whole-blood samples, ages 14-94 years) through intensive testing with machine-learning models. To support reproducible analyses, we developed ugPlot ( https://github.com/a00s/ugplot ), an open-source R/Shiny tool with a graphical user interface that automates model training, testing, and comparison. Initially, we identified 48 transcripts across 13 genes, with some transcripts from the genes OBSCN, PRRT1, and SPTBN4 showing better predictive performance when multiple associated CpGs were analysed together rather than individually. In contrast, for the majority of transcripts, a dominant individual CpG still showed a higher Spearman correlation with age, as seen in established ageing genes such as ELOVL2, FHL2, and TRIM59. Epitage is a transcript-ranking list based on the methylation patterns observed in the analysed dataset. It provides a reproducible framework for prioritising transcripts associated with human ageing and for guiding future epigenetic studies.

Humans↗

Uncertainty assessment of VOC emissions from paint in The Netherlands using the NUSAP system.

We demonstrate an innovative approach to uncertainty assessment known as the NUSAP system, to assess qualitative and quantitative uncertainty for the case of emissions of volatile organic compounds (VOC) from paint in The Netherlands. Using expert elicitation, we identified key sources of error, critical assumptions, and bias in the monitoring process. We assessed pedigree and probabilistic uncertainty of all input quantities. We used four pedigree criteria to assess the strength of the knowledge base: proxy representation, empirical basis, methodological rigour and degree of validation. Using Monte Carlo analysis, we assessed sensitivity and propagation of uncertainty. Results for sensitivity and pedigree were combined in a 'NUSAP Diagnostic Diagram', which effectively highlighted the assumption for VOC percentage of imported paint as the weakest spot in the monitoring of VOC emissions. We conclude that NUSAP facilitates systematic scrutinization of method and underlying assumptions and structures creative thinking on sources of error and bias. It provides a means to prioritise uncertainties and focus research efforts on the potentially most problematic parameters and assumptions, at the same time identifying specific weaknesses in the knowledge base. With NUSAP, nuances of meaning about quantities can be conveyed concisely and clearly, to a degree that is not possible with statistic methods only.

Air Pollutants↗

Priorities in the use of research into ageing.

This paper considers which applications of research into ageing should be supported. It assumes that both applications which enhance the quality of life for the elderly and applications which extend the life-span are desirable, and then considers which should be prioritised. It is argued that in the present state of our knowledge and under present social and medical conditions there are a number of reasons for favouring the improvement of the quality of life over increasing the life-span, and thinking that this is likely to do more good and for more people.

Aged↗

Access, equity and the role of rights in health care.

Modern health care rhetoric promotes choice and individual patient rights as dominant values. Yet we also accept that in any regime constrained by finite resources, difficult choices between patients are inevitable. How can we balance rights to liberty, on the one hand, with equity in the allocation of scarce resources on the other? For example, the duty of health authorities to allocate resources is a duty owed to the community as a whole, rather than to specific individuals. Macro-duties of this nature are founded on the notion of equity and fairness amongst individuals rather than personal liberty. They presume that if hard choices have to be made, they will be resolved according to fair and consistent principles which treat equal cases equally, and unequal cases unequally. In this paper, we argue for greater clarity and candour in the health care rights debate. With this in mind, we discuss (1) private and public rights, (2) negative and positive rights, (3) procedural and substantive rights, (4) sustainable health care rights and (5) the New Zealand booking system for prioritising access to elective services. This system aims to consider: individual need and ability to benefit alongside the resources made available to elective health services in an attempt to give the principles of equity practical effect. We describe a continuum on which the merits of those, sometimes competing, values--liberty and equity--can be evaluated and assessed.

Delivery of Health Care↗

Pharmaceutical policy and the lay public.

Almost every national and supranational health policy document accords high importance to the need to listen to and 'empower' patients. The relationship between pharmaceutical policy and the lay public is not direct but mediated by several actors, including health care workers, patient organisations, industry and, most recently, the media. Although the overall aim of health and pharmaceutical policy is to address the needs of all citizens, there are only a few, well organised groups who are actually consulted and involved in the policymaking process, often with the support of the industry. The reasons for this lack of citizen involvement in health and pharmaceutical policymaking are many, for example: there is no consensus about what public involvement means; there is a predominance of special interest groups with narrow, specific agendas; not all decision makers welcome lay participation; patients and professionals have different rationalities with regard to their views on medicine. Because the lay public and medicine users are not one entity, one of the many challenges facing policy makers today is to identify, incorporate and prioritise the many diverse needs. The authors recommend research which includes studies that look at: lay attitudes towards pharmaceutical policy; lay experiences of drug therapy and how it affects their daily lives; the problem of identifying lay representatives; the relationship between industry and the consumers; the effect of the media on medicine users and on pharmaceutical policy itself. The authors acknowledge that although lay involvement in policy is still in its infancy, some patient organisations have been successful and there are developments towards increased lay involvement in pharmaceutical policymaking.

Community Participation↗

Factors affecting the outcome of acute renal failure among the elderly population in India: a hospital based study.

The spectrum of acute renal failure (ARF) in the elderly population and the factors predicting poor outcome in these patients are not well defined in literature. Identification of risk factors and poor prognostic markers in these patients can help in planning strategies to prevent ARF and to prioritise the utilization of sparse and expensive therapeutic modalities, especially in a developing country like ours. We retrospectively analyzed data of 454 elderly patients (age >or=60 years), detected having ARF in a tertiary care super-speciality hospital in North India, from April 2000 to March 2004. The mean age of this population was 66.4 years with 70.5% being male. 64% patients had more than one precipitating factors for ARF, with volume depletion being the most common precipitating factor (33% cases). Infection/sepsis (21.6%) and drugs (11.5%) were other important precipitating factors. 31.8% were recorded as having oliguric ARF (urine output <400 ml/day) and 33.5% required renal replacement therapy (RRT). Acute peritoneal dialysis was the most frequent form of RRT given (62.5%). Mortality was 41.2% (187 cases), of whom 56 (29.8%) died inspite of recovery from ARF. Among the survivors, 103 patients (22.7%) had complete renal recovery, 141 (31.1%) had partial renal recovery, while 23 (8.6%), remained dialysis dependent. The factors which were found to be associated with increased mortality were; age >or=70 years, presence of previous chronic illness, ARF precipitated by cardiac failure and infection, need for RRT, oliguria and increasing numbers of failed organs. To conclude, ARF among elderly is a common problem in nephrology practice at our institute and is responsible for 48.9% of nephrology admissions/consultations among elderly patients. Majority of these patients are prone to multiple renal insults. Underlying chronic illness, presence of cardiac failure and sepsis, oliguria, need for RRT and increasing number of organ failure is associated with poor outcome.

Acute Kidney Injury↗

Impacts of Climate Change and Related Weather Events on the&#xa0;Health and Wellbeing of Culturally and Linguistically Diverse Communities: A Systematic Review.

BACKGROUND: Vulnerable populations such as culturally and linguistically diverse communities (CALD), ethnic minorities and racial groups face a disproportionate burden of climate change-related health impacts due to a combination of socio-cultural and economic factors, geographic vulnerabilities and health disparities. This review synthesised the existing evidence on the health and wellbeing impacts of climate change and related weather events among CALD communities. METHODS: A narrative synthesis approach was utilised to conduct a systematic review. Three electronic databases (PubMed, Scopus and Web of Science) were searched, identifying 25 studies for appraisal and synthesis. Studies published in the English language from January 2010 to March 2024 were included in the review. RESULTS: The reviewed studies, mostly carried out in the USA, employed varied study designs, and focused on diverse CALD groups such as migrants, farmworkers and racial and ethnic minorities. The included studies addressed broader and specific climate change-related events, ranging from heat-related impacts and hurricanes to occupational heat exposure. CALD communities were found to be more vulnerable to climate change-related negative physical and mental health issues, further exacerbated by poor living conditions, limited access to healthcare, and cultural and language barriers. CONCLUSION: Future efforts by governments, healthcare agencies, employers and research institutions should prioritise multilingual risk communication strategies, providing culturally appropriate health education and healthcare access, housing improvements and the investigation of long-term health impacts of climate change and coping mechanisms adopted among CALD populations.

Climate Change↗

Who cares about cost? Does economic analysis impose or reflect social values?

In a two-stage survey, a cross-section of Australians were questioned about the importance of costs in setting priorities in health care. Generally, respondents felt that it is unfair to discriminate against patients who happen to have a high cost illness and that costs should therefore not be a major factor in prioritising. The majority maintained this view even when confronted with its implications in terms of the total number of people who could be treated and their own chance of receiving treatment if they fall ill. Their position cannot be discarded as irrational, as it is consistent with a defensible view of utility. However, the results suggest that the concern with allocative efficiency, as usually envisaged by the economists, is not shared by the general public and that the cost-effectiveness approach to assigning priorities in health care may be imposing an excessively simple value system upon resource allocation decision-making.

Attitude to Health↗

A multicentre survey of hand hygiene practice in intensive care units.

A detailed survey of hand hygiene in 16 intensive care units (ICUs) in Yorkshire was undertaken with the aim of following up the results of a national survey of infection control policies and practices which had been conducted in 1990 (Inglis et al., Br J Anaesthesia 1992; 68, 216-220). The main problems associated with infection control were identified as: the limited relevance of some infection control policies to the specialist nature of intensive care, poor compliance by nurses to local infection control policies, sub-optimal hand hygiene by all healthcare professionals and a need for more effective communication of research-based infection control recommendations in the ICU. Our results suggest that hand hygiene practice in the ICU is sub-optimal as a consequence of ineffective communication of infection control recommendations, insufficient promotion and enforcement of agreed research-based infection control practices, and a deficiency in infection control education. The current methods of communicating infection control recommendations have a limited effect on compliance rates in the ICU and are not evaluated adequately. Recommendations for further development in this field are to prioritise surveillance of infection rates in ICUs and to feedback infection rates to intensive care staff, to identify local priorities for infection control and to introduce continuous infection control education for all healthcare professionals. Further research is required to investigate and understand why educated health professionals are not complying with recommended research-based infection control practices.

Clinical Protocols↗

The validation event: a critical appraisal?

Apart from the perennial concern with finance, questions of 'quality' and 'accountability' will be the principle themes in the higher education debate in the 1990s. The whole issue of 'quality' and 'accountability' has become critically important to the success or otherwise of colleges of nursing and midwifery in convincing their multiple stakeholders (clients, patients, students and purchasers) that they should have a place in the marketing of nursing and midwifery education. The validation process is an important component of the formalized quality assurance mechanism of a course. There have, however, been little or no empirical data relating to the effect of validation processes on quality of courses and, more important, in the long term, quality of care. The following issues are explored in the paper. How are 'quality' and 'accountability' defined within the context of a market orientated system? How is 'peer review' to be interpreted within a purchaser led system? Are practice outcomes prioritised within educationally led, practice-based courses? Is there a part to play for continuing external regulation? We suggest that recent developments in nursing and midwifery education have often been undermined, during validation events, by structural processes for conformity. Such a regression to the conventional has been strengthened by the absence of new conceptions of quality deliberately designed to match these innovatory courses. Conceptions, that is, framed in terms distinct from the traditional model in which quality in higher education tends to be regarded as largely an attribute of disciplinary knowledge. Finally, we suggest that the decisive determinant of professional skill, is the personal standards, the professionalism and the self-respect of the individual teacher.

Accreditation↗