Progress towards malaria elimination in the Greater Mekong Subregion: perspectives from the World Health Organization.

Malaria remains a global health challenge, disproportionately affecting vulnerable communities. Despite substantial progress, the emergence of anti-malarial drug resistance poses a constant threat. The Greater Mekong Subregion (GMS), which includes Cambodia, China's Yunnan province, Lao People's Democratic Republic, Myanmar, Thailand, and Viet Nam has been the epicentre for the emergence of resistance to successive generations of anti-malarial therapies. From the perspective of the World Health Organization (WHO), this article considers the collaborative efforts in the GMS, to contain Plasmodium falciparum artemisinin partial resistance and multi-drug resistance and to advance malaria elimination. The emergence of artemisinin partial resistance in the GMS necessitated urgent action and regional collaboration resulting in the Strategy for Malaria Elimination in the Greater Mekong Subregion (2015-2030), advocating for accelerated malaria elimination interventions tailored to country needs, co-ordinated and supported by the WHO Mekong malaria elimination programme. The strategy has delivered substantial reductions in malaria across all GMS countries, with a 77% reduction in malaria cases and a 97% reduction in malaria deaths across the GMS between 2012 and 2022. Notably, China was certified malaria-free by WHO in 2021. Countries' ownership and accountability have been pivotal, with each GMS country outlining its priorities in strategic and annual work plans. The development of strong networks for anti-malarial drug resistance surveillance and epidemiological surveillance was essential. Harmonization of policies and guidelines enhanced collaboration, ensuring that activities were driven by evidence. Challenges persist, particularly in Myanmar, where security concerns have limited recent progress, though an intensification and acceleration plan aims to regain momentum. Barriers to implementation can slow progress and continuing innovation is needed. Accessing mobile and migrant populations is key to addressing remaining transmission foci, requiring effective cross-border collaboration. In conclusion, the GMS has made significant progress towards malaria elimination, particularly in the east where several countries are close to P. falciparum elimination. New and persisting challenges require sustained efforts and continued close collaboration. The GMS countries have repeatedly risen to every obstacle presented, and now is the time to re-double efforts and achieve the 2030 goal of malaria elimination for the region.

Formation of Trideuteromethylated Artifacts of Pyrrole-Containing Natural Products.

Pyrrole-containing natural products form a large group of structurally diverse compounds that occur in both terrestrial and marine organisms. In the present study the formation of trideuteromethylated artifacts of pyrrole-containing natural products was investigated, focusing on the discorhabdins. Three deuterated discorhabdins, 1, 3, and 5, were identified to be isolation procedure artifacts caused by the presence of DMSO-d6 during NMR sample preparation and handling. Three additional semisynthetic derivatives, 7-9, were made during the investigation of the mechanism of formation, which was shown to be driven by trideuteromethyl radicals in the presence of water, methanol, TFA, and traces of iron in the deuterated solvent. Generation of trideuteromethylated artifacts was also confirmed for other classes of pyrrole-containing metabolites, namely, makaluvamines, tambjamines, and dibromotryptamines, which had also been dissolved in DMSO-d6 during the structure elucidation process. Semisynthetic discorhabdins were assessed for antiproliferative activity against a panel of human tumor cell lines, and 14-trideuteromethyldiscorhabdin L (3) averaged low micromolar potency.

Technical Note: Use of a Novel Bacterial Culture Sampling Device for Pooled Whole Blood Platelets.

OBJECTIVE: Transfusion associated sepsis is a serious risk after platelet transfusion. Although platelet culture can be performed to avoid such risk, culture results are often available after transfusion due to the 4-hour shelf-life after pooling. To decrease such risk, we implemented a needleless closed system device to culture for contamination before pooling and release for transfusion. METHODS: We customized a needleless device to permit sterile sampling of whole blood platelets without retrograde or cross-contamination. Then aliquots of platelets were injected into culture media for detection of aerobic organisms and cultured for 24 hours but released for transfusion after 12 hours of negative culture. RESULTS: In a period of two years, we used this device in 5,741 whole blood derived pooled platelets and only 24 units tested positive (0.4%) but none of initial positive was later confirmed. There were 11 Staphylococcus and 9 Bacillus species identified. All but one of the positive units were discarded; there was no clinical impact in the patient who received the positive unit. CONCLUSION: This device allows for sampling of whole blood derived platelets before pooling, warranting a transfusion of a culture negative unit after 12 hours of negative culture, consequently reducing transfusion of bacterially contaminated whole blood derived pooled platelets.

Remote Evidence-Based Health Promotion Programs During COVID: A National Evaluation of Reach and Implementation for Older Adult Health Equity.

INTRODUCTION.: Evidence-based health promotion programs (EBPs) support older adults where they live, work, pray, play, and age. COVID-19 placed a disproportionate burden on this population, especially those with chronic conditions. In-person EBPs shifted to remote delivery via video-conferencing, phone, and mail during the pandemic, creating opportunities and challenges for older adult health equity. METHOD.: In 2021-2022, we conducted a process evaluation of remote EBPs by purposively sampling diverse U.S. organizations and older adults (people of color, rural, and/or with disabilities). The Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) + Equity framework was used to understand program reach and implementation, including FRAME to describe adaptations for remote delivery. Analyses include descriptive statistics and thematic analysis of participant and provider surveys and interviews, and joint display tables to compare learnings. RESULTS.: Findings from 31 EBPs through 198 managers/leaders and 107 organizations suggest remote delivery increases EBP reach by improving access for older adults who are underserved. For programs requiring new software or hardware, challenges remain reaching those with limited access to-or comfort using-technology. Adaptations were to context (e.g., shorter, smaller classes with longer duration) and for equity (e.g., phone formats, autogenerated captioning); content was unchanged except where safety was concerned. Implementation is facilitated by remote delivery guidelines, distance training, and technology support; and hindered by additional time, staffing, and resources for engagement and delivery. CONCLUSIONS.: Remote EBP delivery is promising for improving equitable access to quality health promotion. Future policies and practices must support technology access and usability for all older adults.

Prospective, open-label, multicenter clinical study to assess the performance of a new donation system for the collection of source plasma.

BACKGROUND: Safe, efficient, and reliable innovations among donation systems are needed to meet the growing global demand for source plasma. This study assessed the ability of a new donation system to collect appropriate product weights based on the US Food and Drug Administration nomogram for source plasma collections. Procedure duration and safety endpoints were also collected. STUDY DESIGN AND METHODS: The Rika Plasma Donation System (Terumo BCT, Inc., Lakewood, CO) was evaluated in a prospective, open-label, multicenter study. Healthy adults meeting FDA and Plasma Protein Therapeutics Association requirements for source plasma donor eligibility were consented and enrolled in the study resulting in 124 evaluable products. RESULTS: The target product collection weights (ie, including plasma and anticoagulant) by participant weight category were: 705 g (110-149 lbs), 845 g (150-174 lbs), and 900 g (≥175 lbs). The mean reported product collection weights by participant weight category were 705.0 ± 0.00, 845.0 ± 0.20, and 899.9 ± 0.31 g, respectively. The mean overall procedure time was 31.5 ± 5.41 minutes. The mean procedure times by participant weight category were 25.6 ± 3.13, 30.5 ± 4.45, and 33.7 ± 4.80 minutes, respectively. Procedure-emergent adverse events (PEAEs) occurred in five participants. All PEAEs were consistent with known risks for apheresis donation, and none were related to the donation system. CONCLUSIONS: The new donation system collected the target product collection weight in 100% of evaluable products. The mean procedure collection time was 31.5 minutes. The system is a new efficient platform that consistently collects the appropriate weight of the source plasma.

Contact: William S. Burroughs's philosophy of love.

The present psychobiography took up the three main psychoanalytic conceptions of love to illuminate the psychological development of famed experimental writer William Seward Burroughs (1914-1997). The study found evidence of all three concepts of love in the subject's life strategies: (1) Love as cathexis was present in Burroughs' fascination with centipedes and other vermin that appeared in his dreams and which symbolised, in part, his terror over early childhood traumas as well as his concomitant struggle to integrate sex with intimacy. (2) Love as eroto-philiac fusion was observed in Burroughs' unstable and even exploitative relationships with others. This tendency was most salient in Burroughs' abortive attempts to seduce straight men, as well as in his failed efforts to be a traditional husband and father. (3) Reparative love became the subject's primary mode of interaction late in life. The study showed that, in his declining years, Burroughs was able to overcome partially the maladaptive strategies of his early life through his numerous pet cats, upon whom he projected aspects of his past romantic partners and friends.

Digitally enabled hemovigilance allows real time response to transfusion reactions.

BACKGROUND: Transfusion carries a risk of transfusion reaction that is often underdiagnosed due to reliance on passive reporting. The study investigated the utility of digital methods to identify potential transfusion reactions, thus allowing real-time intervention for affected patients. METHOD: The hemovigilance unit monitored 3856 patients receiving 43,515 transfusions under the hemovigilance program. Retrospective comparison data included 298,498 transfusions. Transfusion medicine physicians designed and validated algorithms in the electronic health record that analyze discrete data, such as vital sign changes, to assign a risk score during each transfusion. Dedicated hemovigilance nurses remotely monitor all patients and perform real-time chart reviews prioritized by risk score. When a reaction is suspected, a hemovigilance trained licensed clinician responds to manage the patient and ensure data collection. Board-certified transfusion medicine physicians reviewed data and classified transfusion reactions under various categories according to the Centers for Disease Control hemovigilance definitions. RESULTS: Transfusion medicine physicians diagnosed 564 transfusion reactions (1.3% of transfusions)-a 524% increase compared to the previous passive reporting. The rapid response provider reached the bedside on average at 12.4 min demonstrating logistic feasibility. While febrile reactions were most diagnosed, recognition of transfusion-associated circulatory overload demonstrated the greatest relative increase. Auditing and education programs further enhanced transfusion reaction awareness. DISCUSSION: The model of digitally-enabled expert real-time review of clinical data that prompts rapid response improved recognition of transfusion reactions. This approach could be applied to other patient deterioration events such as early identification of sepsis.

Oncology Patients Who Develop Transfusion-Associated Circulatory Overload: An Observational Study.

BACKGROUND: Transfusion-associated circulatory overload (TACO) is a largely preventable transfusion complication that results in significant morbidity and mortality. Cancers, related treatments, and comorbidities are among the factors that can predispose patients to TACO, but currently there are limited data on this topic in the literature. METHODS: We collected data retrospectively from the electronic health records of 93 adult patients with cancer who met Centers for Disease Control and Prevention (CDC) criteria for TACO from July 1, 2019, through October 31, 2020. The parameters we studied included demographics, comorbidities, treatment modalities, transfusion practices, and outcomes. We summarized data by means and ranges for continuous variables, and proportions for categorical variables. RESULTS: During the study period, the incidence of TACO among oncology patients was 0.84 per 1000 transfusions (95% CI, 0.68-1.02), representing 6.6% of all reactions. This percentage is high, compared with 1%-6% among other populations. Unique characteristics such as hematology malignancy (75.3%), receipt of cardiotoxic chemotherapy (87.1%), pneumonia (57.0%), preexisting oxygen use (59.1%), dyspnea (62.4%), hypertension (55.9%), renal insufficiency (46.2%), daily use of corticosteroids (43.0%), daily use of diuretics (40.9%), daily use of beta-blockers (36.6%), and elevated NT-proBNP (33.3%) were frequently observed in these group of oncology patients. CONCLUSIONS: Our study indicates that oncology patients have unique factors that may lead to diagnosis of TACO. Developing appropriate guidelines that apply to oncology patients, in addition to those set forth by the CDC, should be considered. Implementation by ordering healthcare providers of a tools that can predict TACO can help in early recognition and mitigation of TACO.

A chemical probe based on the PreQ1 metabolite enables transcriptome-wide mapping of binding sites.

The role of metabolite-responsive riboswitches in regulating gene expression in bacteria is well known and makes them useful systems for the study of RNA-small molecule interactions. Here, we study the PreQ1 riboswitch system, assessing sixteen diverse PreQ1-derived probes for their ability to selectively modify the class-I PreQ1 riboswitch aptamer covalently. For the most active probe (11), a diazirine-based photocrosslinking analog of PreQ1, X-ray crystallography and gel-based competition assays demonstrated the mode of binding of the ligand to the aptamer, and functional assays demonstrated that the probe retains activity against the full riboswitch. Transcriptome-wide mapping using Chem-CLIP revealed a highly selective interaction between the bacterial aptamer and the probe. In addition, a small number of RNA targets in endogenous human transcripts were found to bind specifically to 11, providing evidence for candidate PreQ1 aptamers in human RNA. This work demonstrates a stark influence of linker chemistry and structure on the ability of molecules to crosslink RNA, reveals that the PreQ1 aptamer/ligand pair are broadly useful for chemical biology applications, and provides insights into how PreQ1, which is similar in structure to guanine, interacts with human RNAs.

A series of developmental validation tests for Number of Contributors platforms: Exemplars using NOCIt and a neural network.

Complex DNA mixtures are challenging to interpret and require computational tools that aid in that interpretation. Recently, several computational methods that estimate the number of contributors (NOC) to a sample have been developed. Unlike analogous tools that interpret profiles and report LRs, NOC tools vary widely in their operational principle where some are Bayesian and others are machine learning tools. Conjunctionally, NOC tools may return a single n estimate, or a distribution on n. This vast array of constructs, coupled with a gap in standardized methods by which to validate NOC systems, warrants an exploration into the measures by which differing NOC systems might be tested for operations. In the current paper, we use two exemplar NOC systems: a probabilistic system named NOCIt, which renders an a posteriori probability (APP) distribution on the number of contributors given an electropherogram and an artificial neural network (ANN). NOCIt is a continuous Bayesian inference system incorporating models of peak height, degradation, differential degradation, forward and reverse stutter, noise and allelic drop-out while considering allele frequencies in a reference population. The ANN is also a continuous method, taking all the same features (barring degradation) into account. Unlike its Bayesian counterpart, it demands substantively more data to parameterize, requiring synthetic data. We explore each system's performance by conducting tests on 214 PROVEDIt mixtures where the limit of detection was 1-copy of DNA. We found that after a lengthy training period of approximately 24 h, the ANN's evaluation process was very fast and perfectly repeatable. In contrast, NOCIt only took a few minutes to train but took tens of minutes to complete each sample and was less repeatable. In addition, it rendered a probability distribution that was more sensitive and specific, affording a reasonable method by which to report all reasonable n that explain the evidence for a given sample. Whatever the method, by acknowledging the inherent differences between NOC systems, we demonstrate that validation constructs will necessarily be guided by the needs of the forensic domain and be dependent upon whether the laboratory seeks to assign a single n or range of n.

The Emperor of Fashion's New Starts: Creativity and Meaning in Life in Karl Lagerfeld.

During his lifetime, Karl Otto Lagerfeld (1933-2018) attained such industry renown that he became widely known as the Emperor of Fashion. Lagerfeld ran several fashion houses, such as Chanel and Fendi, leading them to unprecedented profits. He also created his own fashion label. Owing to his unremitting pursuit of excellence through creative expression, Lagerfeld's creativity, energy and intuition for fashion trends seemed only to expand throughout his long career. The authors suggest that, through his creative approach to fashion, architecture, and publishing, Lagerfeld articulated and refined a core set of values-such as "Bildung," "lightness" and "the unexpected"-that served as a Diltheyan "nexus" linking the Prussian-born designer with the global consumer. The authors apply two specific creativity theories to Lagerfeld's life and work, namely the mini-c, little-c, Pro-c and Big-C creativity theory and Sternberg's WICS-model (wisdom, intelligence and creativity). The article uses a psychobiographical case study design formulated according to a research paradigm of modern hermeneutics. First- and third-person data on Lagerfeld were collected and evaluated through a hermeneutically-informed syntho-analysis. Research ethics were followed. The findings demonstrate the interplay of mini-c, little-c, Pro-c and Big-C creativity throughout the subject's lifetime, as well as the subject's application of WICS, both of which led to the subject's worldwide success. Conclusions are drawn and recommendations for future research and practice are provided.

Recifin A, Initial Example of the Tyr-Lock Peptide Structural Family, Is a Selective Allosteric Inhibitor of Tyrosyl-DNA Phosphodiesterase I.

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a molecular target for the sensitization of cancer cells to the FDA-approved topoisomerase inhibitors topotecan and irinotecan. High-throughput screening of natural product extract and fraction libraries for inhibitors of TDP1 activity resulted in the discovery of a new class of knotted cyclic peptides from the marine sponge Axinella sp. Bioassay-guided fractionation of the source extract resulted in the isolation of the active component which was determined to be an unprecedented 42-residue cysteine-rich peptide named recifin A. The native NMR structure revealed a novel fold comprising a four strand antiparallel ß-sheet and two helical turns stabilized by a complex disulfide bond network that creates an embedded ring around one of the strands. The resulting structure, which we have termed the Tyr-lock peptide family, is stabilized by a tyrosine residue locked into three-dimensional space. Recifin A inhibited the cleavage of phosphodiester bonds by TDP1 in a FRET assay with an IC50 of 190 nM. Enzyme kinetics studies revealed that recifin A can specifically modulate the enzymatic activity of full-length TDP1 while not affecting the activity of a truncated catalytic domain of TDP1 lacking the N-terminal regulatory domain (Δ1-147), suggesting an allosteric binding site for recifin A on the regulatory domain of TDP1. Recifin A represents both the first of a unique structural class of knotted disulfide-rich peptides and defines a previously unseen mechanism of TDP1 inhibition that could be productively exploited for potential anticancer applications.

Strengthening policy coding methodologies to improve COVID-19 disease modeling and policy responses: a proposed coding framework and recommendations.

BACKGROUND: In recent months, multiple efforts have sought to characterize COVID-19 social distancing policy responses. These efforts have used various coding frameworks, but many have relied on coding methodologies that may not adequately describe the gradient in social distancing policies as states "re-open." METHODS: We developed a COVID-19 social distancing intensity framework that is sufficiently specific and sensitive to capture this gradient. Based on a review of policies from a 12 U.S. state sample, we developed a social distancing intensity framework consisting of 16 domains and intensity scales of 0-5 for each domain. RESULTS: We found that the states with the highest average daily intensity from our sample were Pennsylvania, Washington, Colorado, California, and New Jersey, with Georgia, Florida, Massachusetts, and Texas having the lowest. While some domains (such as restaurants and movie theaters) showed bimodal policy intensity distributions compatible with binary (yes/no) coding, others (such as childcare and religious gatherings) showed broader variability that would be missed without more granular coding. CONCLUSION: This detailed intensity framework reveals the granularity and nuance between social distancing policy responses. Developing standardized approaches for constructing policy taxonomies and coding processes may facilitate more rigorous policy analysis and improve disease modeling efforts.

Transfusion reactions in pediatric and adolescent young adult haematology oncology and immune effector cell patients.

BACKGROUND: Active surveillance for transfusion reactions is critically important among pediatric patients undergoing chemotherapy. Among pediatric-adolescent-young-adult (AYA) hematology/oncology patients, who have been typically excluded from transfusion reaction studies, this profile remains poorly characterized. METHODS: We assessed the incidence and clinical characteristics of transfusion reactions (n = 3246 transfusions) in this population (n = 201 patients) at our center. FINDINGS: The incidence of adjudicated transfusion reactions was 2·04%. The incidence was higher for platelet (2·78%) compared to packed red blood cell transfusions (1·49%) (p = 0·0149). The majority (61·4%) of all reactions were classified as febrile non-haemolytic transfusion, while 35·7% were considered allergic, and 2·9% were classified as transfusion-associated circulatory overload. The incidence of transfusion reactions in patients who were pre-medicated was higher (2·51%) than in patients who were not (1·52%) (p = 0·0406). Sub-set analysis revealed a 3·95% incidence of adjudicated transfusion reactions among recipients of immune effector cells (IECs) (n = 3), all of which occurred during the potential window for cytokine release syndrome; two-thirds of these reactions were severe/potentially life-threatening. INTERPRETATION: The incidence of transfusion reactions among pediatric-AYA hematology/oncology patients may be lower than the general pediatric population. Patients with a prior history of transfusion reactions and those receiving platelet transfusions may be at higher risk for reaction. From our limited sample, IEC recipients may be at risk for severe transfusion reactions. Large multi-center prospective studies are needed to characterize transfusion reactions in this population. Appropriate characterization of reactions in this population may inform risk stratification and mitigate missed opportunities for prompt recognition and appropriate management. FUNDING: None.

Multiphase Assembly of Small Molecule Microcrystalline Peptide Hydrogel Allows Immunomodulatory Combination Therapy for Long-Term Heart Transplant Survival.

Combination therapies that target multiple pathways involved in immune rejection of transplants hold promise for patients in need of restorative surgery. Herein, a noninteracting multiphase molecular assembly approach is developed to crystallize tofacitinib, a potent JAK1/3 inhibitor, within a shear-thinning self-assembled fibrillar peptide hydrogel network. The resulting microcrystalline tofacitinib hydrogel (MTH) can be syringe-injected directly to the grafting site during surgery to locally deliver the small molecule. The rate of drug delivered from MTH is largely controlled by the dissolution of the encapsulated microcrystals. A single application of MTH, in combination with systemically delivered CTLA4-Ig, a co-stimulation inhibitor, affords significant graft survival in mice receiving heterotopic heart transplants. Locoregional studies indicate that the local delivery of tofacitinib at the graft site enabled by MTH is required for the observed enhanced graft survival.

Developing Pathology Measures for the Quality Payment Program-Part II: Overcoming Challenges With Data Capture to Maximize Reimbursement.

CONTEXT.­: Quality measures are a cornerstone in measuring physicians' performance within the Centers for Medicare & Medicaid Services' Quality Payment Program (QPP). Clinicians' performance on quality measures and other categories within the QPP determines Medicare part B payment adjustments. Driven by evidence-based clinical practice guidelines, quality measures should focus on high-priority facets of health care, support a desired patient outcome, and address an area with evidence of a gap or variation in provider performance. OBJECTIVE.­: To meet the goals of the QPP, a broad array of quality measures must be developed that allows pathologists the flexibility to choose activities and measures most meaningful to their practice and patient population while also trying to mitigate the challenges of implementation and data collection. DESIGN.­: In this second manuscript of the series, we present the development of additional College of American Pathologists-developed quality payment measures for use in the QPP. We also discuss the relationship of quality measure reporting with reimbursement and the challenges with capturing data for quality reporting. RESULTS.­: The College of American Pathologists identified 23 new measures for quality performance reporting that reflect rigorous clinical evidence and address areas in need of performance improvement. CONCLUSIONS.­: Development of quality measures is a necessary and ongoing effort within the College of American Pathologists. Increased awareness about pathology-specific issues in measure development and reporting is essential to ensuring pathology's ability to demonstrate value and meaningfully participate in the QPP.

Overview of COVID-19 testing and implications for otolaryngologists.

BACKGROUND: Testing for SARS-CoV-2 is important for decision making prior to surgery in otolaryngology. An understanding of current and developing testing methods is important for interpreting test results. METHODS: We performed a literature review of current evidence surrounding SARS-CoV-2 diagnostic testing highlighting its utility, limitations, and implications for otolaryngologists. RESULTS: The currently accepted RT-PCR test for SARS-CoV-2 has varying sensitivity according to which subsite of the aerodigestive tract is sampled. Nasal swab sensitivities appear to be about 70%. Chest CT imaging for screening purposes is not currently recommended. CONCLUSION: Due to the current sensitivity of RT-PCR based testing for SARS-CoV-2, a negative test cannot rule out COVID-19. Full PPE should be worn during high-risk procedures such as aerosol generating procedures even if testing is negative. Patients who test positive during screening should have their surgeries postponed if possible until asymptomatic and have tested negative for SARS-CoV-2.

Selective Reactivity of Anti-Japanese Encephalitis Virus NS4B Antibody Towards Different Flaviviruses.

Studies investigating West Nile virus (WNV) NS4B protein function are hindered by the lack of an antibody recognizing WNV NS4B protein. Few laboratories have produced WNV NS4B antibodies, and none have been shown to work consistently. In this report, we describe a NS4B antibody against Japanese encephalitis virus (JEV) NS4B protein that cross-reacts with the NS4B protein of WNV but not of dengue virus (DENV). This JEV NS4B antibody not only recognizes WNV NS4B in infected cells, but also recognizes the NS4B protein expressed using transfection. It is evident from this data that the JEV NS4B antibody is specific to NS4B of WNV but not to NS4B of the four DENV serotypes. The specificity of this antibody may be due to the notable differences that exist between the amino acid sequence identity and antigenic relationships within the NS4B protein of the WNV, DENV, and JEV.

Outline for a future psychiatry: the transcendent meaning model (TMM).

The now-dominant medical model of psychiatry has recently been challenged by the post-psychiatry movement. However, the former discounts the agential or subjective aspect of the human being; the latter misses the axiological aspect. A new model is proposed-the Transcendent Meaning Model (TMM)-that nests the individual person within the social (the interperson), and the social within the transcendent or ideological. The study concludes that TMM, with its integration of the personal, the social and the religious-ideological with the material, is a viable blueprint for a future psychiatry that can address some of the current model's vulnerabilities.