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Topological spaces in general, and the real numbers in particular, have the characteristic of exhibiting a 'continuity structure', one that can be examined from the vantage point of Baire category or of Lebesgue measure. Though they are in some sense dual, work over the last half-century has shown that it is the former, topological view, that has pride of place since it reveals a much richer structure that draws from, and gives back to, areas such as analytic sets, infinite games, probability, infinite combinatorics, descriptive set theory and topology. Keeping prerequisites to a minimum, the authors provide a new exposition and synthesis of the extensive mathematical theory needed to understand the subject's current state of knowledge, and they complement their presentation with a thorough bibliography of source material and pointers to further work. The result is a book that will be the standard reference for all researchers in the area.
The genus Maculabatis is a group of batoid rays from the Dasyatidae family, consisting of two main complexes: the gerrardi (spotted species) and the pastinacoides (plain species). This study investigated the diversity within the Maculabatis gerrardi complex, revealing the presence of two distinct geographical lineages, with a potential new species captured off the coast of Mozambique. Molecular analysis showed a significant divergence: COI sequences from Mozambique specimens exhibited over 99% similarity with M. gerrardi from South Africa but more than 2% divergence from those in the Indo-Pacific. Phylogenetic analysis identified two distinct subclades, suggesting at least two hidden lineages within the genus Maculabatis and consequently possible new undescribed species within M. gerrardi complex. These findings emphasize the importance of conducting additional research that integrates both morphological and molecular methods to better understand the group's diversity and evolutionary dynamics, ultimately supporting the development of effective conservation strategies.
Being married may protect late-life cognition. Less is known about living arrangement among unmarried adults and mechanisms such as brain health (BH) and cognitive reserve (CR) across race and ethnicity or sex/gender. The current study examines (1) associations between marital status, BH, and CR among diverse older adults and (2) whether one’s living arrangement is linked to BH and CR among unmarried adults.
Method:
Cross-sectional data come from the Washington Heights-Inwood Columbia Aging Project (N = 778, 41% Hispanic, 33% non-Hispanic Black, 25% non-Hispanic White; 64% women). Magnetic resonance imaging (MRI) markers of BH included cortical thickness in Alzheimer’s disease signature regions and hippocampal, gray matter, and white matter hyperintensity volumes. CR was residual variance in an episodic memory composite after partialing out MRI markers. Exploratory analyses stratified by race and ethnicity and sex/gender and included potential mediators.
Results:
Marital status was associated with CR, but not BH. Compared to married individuals, those who were previously married (i.e., divorced, widowed, and separated) had lower CR than their married counterparts in the full sample, among White and Hispanic subgroups, and among women. Never married women also had lower CR than married women. These findings were independent of age, education, physical health, and household income. Among never married individuals, living with others was negatively linked to BH.
Conclusions:
Marriage may protect late-life cognition via CR. Findings also highlight differential effects across race and ethnicity and sex/gender. Marital status could be considered when assessing the risk of cognitive impairment during routine screenings.
In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
The incidence of cognitive decline is rising, leading to increased attention on the preventive role of healthy foods on brain function. Previous reviews including primarily observational studies suggested that dietary proteins may improve cognitive performance, but evidence from individual randomised controlled trials (RCT) is less consistent. Therefore, this systematic review examined the long-term effects of dietary proteins from RCT, considering both their amount and type, on cognitive performance (psychomotor speed and attention, executive function, memory and global cognition). Alterations in cerebral blood flow (CBF) – a validated brain vascular function marker – were also considered. A total of 4747 studies were identified through a systematic search, resulting in twenty-three included papers reporting effects on cognitive performance (n = 23) and CBF (n = 3). Improvements were observed in three out of the nine studies that evaluated psychomotor speed which compared a dietary protein intervention with a non-protein or lower-protein control. Of the six beneficial observations on working memory (n = 12), declarative memory (n = 10) and visuospatial memory (n = 10), five were nut interventions from three different trials. Limited studies focusing on global cognition suggested that specific target populations, namely subacute stroke or dementia, may benefit more than healthy individuals from increased dietary protein intake. From the three studies involving CBF, improvements in regional blood flow were associated with most cognitive performance outcomes. The comparative effects of different protein types warrant further investigation. Overall, this review encourages additional research into protein-rich foods or supplements which could potentially prevent or mitigate cognitive decline.
Accelerating COVID-19 Treatment Interventions and Vaccines (ACTIV) was initiated by the US government to rapidly develop and test vaccines and therapeutics against COVID-19 in 2020. The ACTIV Therapeutics-Clinical Working Group selected ACTIV trial teams and clinical networks to expeditiously develop and launch master protocols based on therapeutic targets and patient populations. The suite of clinical trials was designed to collectively inform therapeutic care for COVID-19 outpatient, inpatient, and intensive care populations globally. In this report, we highlight challenges, strategies, and solutions around clinical protocol development and regulatory approval to document our experience and propose plans for future similar healthcare emergencies.
The United States Government (USG) public-private partnership “Accelerating COVID-19 Treatment Interventions and Vaccines” (ACTIV) was launched to identify safe, effective therapeutics to treat patients with Coronavirus Disease 2019 (COVID-19) and prevent hospitalization, progression of disease, and death. Eleven original master protocols were developed by ACTIV, and thirty-seven therapeutic agents entered evaluation for treatment benefit. Challenges encountered during trial implementation led to innovations enabling initiation and enrollment of over 26,000 participants in the trials. While only two ACTIV trials continue to enroll, the recommendations here reflect information from all the trials as of May 2023. We review clinical trial implementation challenges and corresponding lessons learned to inform future therapeutic clinical trials implemented in response to a public health emergency and the conduct of complex clinical trials during “peacetime,” as well.
This manuscript addresses a critical topic: navigating complexities of conducting clinical trials during a pandemic. Central to this discussion is engaging communities to ensure diverse participation. The manuscript elucidates deliberate strategies employed to recruit minority communities with poor social drivers of health for participation in COVID-19 trials. The paper adopts a descriptive approach, eschewing analysis of data-driven efficacy of these efforts, and instead provides a comprehensive account of strategies utilized. The Accelerate COVID-19 Treatment Interventions and Vaccines (ACTIV) public–private partnership launched early in the COVID-19 pandemic to develop clinical trials to advance SARS-CoV-2 treatments. In this paper, ACTIV investigators share challenges in conducting research during an evolving pandemic and approaches selected to engage communities when traditional strategies were infeasible. Lessons from this experience include importance of community representatives’ involvement early in study design and implementation and integration of well-developed public outreach and communication strategies with trial launch. Centralization and coordination of outreach will allow for efficient use of resources and the sharing of best practices. Insights gleaned from the ACTIV program, as outlined in this paper, shed light on effective strategies for involving communities in treatment trials amidst rapidly evolving public health emergencies. This underscores critical importance of community engagement initiatives well in advance of the pandemic.
The Accelerating COVID-19 Therapeutic Interventions and Vaccines Therapeutic-Clinical Working Group members gathered critical recommendations in follow-up to lessons learned manuscripts released earlier in the COVID-19 pandemic. Lessons around agent prioritization, preclinical therapeutics testing, master protocol design and implementation, drug manufacturing and supply, data sharing, and public–private partnership value are shared to inform responses to future pandemics.
The categorisation of personality pathology into discrete disorders has been an enduring standard. However, dimensional models of personality are becoming increasingly prominent, in part owing to their superior validity and clinical utility. We contend that dimensional models also offer a unique advantage in treating mental illness. Namely, psychotherapy approaches and the components of dimensional models of personality can both be arranged hierarchically, from general to specific factors, and aligning these hierarchies provides a sensible framework for planning and implementing treatment. This article begins with a brief review of dimensional models of personality and their supporting literature. We then outline a multidimensional framework for treatment and present an illustrative fictitious clinical case before ending with recommendations for future directions in the field.
Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.
Methods
We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.
Results
The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).
Conclusion
The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.
Depression is an independent risk factor for cardiovascular disease (CVD), but it is unknown if successful depression treatment reduces CVD risk.
Methods
Using eIMPACT trial data, we examined the effect of modernized collaborative care for depression on indicators of CVD risk. A total of 216 primary care patients with depression and elevated CVD risk were randomized to 12 months of the eIMPACT intervention (internet cognitive-behavioral therapy [CBT], telephonic CBT, and select antidepressant medications) or usual primary care. CVD-relevant health behaviors (self-reported CVD prevention medication adherence, sedentary behavior, and sleep quality) and traditional CVD risk factors (blood pressure and lipid fractions) were assessed over 12 months. Incident CVD events were tracked over four years using a statewide health information exchange.
Results
The intervention group exhibited greater improvement in depressive symptoms (p < 0.01) and sleep quality (p < 0.01) than the usual care group, but there was no intervention effect on systolic blood pressure (p = 0.36), low-density lipoprotein cholesterol (p = 0.38), high-density lipoprotein cholesterol (p = 0.79), triglycerides (p = 0.76), CVD prevention medication adherence (p = 0.64), or sedentary behavior (p = 0.57). There was an intervention effect on diastolic blood pressure that favored the usual care group (p = 0.02). The likelihood of an incident CVD event did not differ between the intervention (13/107, 12.1%) and usual care (9/109, 8.3%) groups (p = 0.39).
Conclusions
Successful depression treatment alone is not sufficient to lower the heightened CVD risk of people with depression. Alternative approaches are needed.
In this survey of 31 hospitals, large metropolitan facilities had a 9.5-fold odds of reporting preparedness for special pathogens; hospitals with special pathogens teams had a 14.3-fold odds of reporting preparedness for special pathogens. In the postpandemic world, healthcare institutions must invest in special pathogen responses to maximize patient safety.
The harmful consumption of alcohol is known for how tortuous its management can be in mental health, encouraging introspection of it as a serious problem is perhaps the main key to starting to battle against its damaging influence on the development of a functional and full life.
Objectives
To describe a clinical case showing an unpredictible complication in an alcohol detoxification process.
Methods
54-year-old man, native of Cádiz, widowed for half a decade, without children. He resides with his parents in the family home. Currently unemployed for approximately a year. He has previously worked in the IT sector. As a notable somatic history, we found long-established arterial hypertension and a total hip replacement. He has been under irregular follow-up with a mental health team for anxiety-depressive symptoms in the context of grief. He goes to the emergency service brought by his family to begin the detoxification process in the hospital setting. He acknowledges ethanol consumption since he was widowed, which began when he awakes; quantities that ranged between one or up to three bottles of distilled liquor per day, generally consumption is in the home environment. A little less than a year ago, he began to isolate himself in his room and abandon his self-care, eating increasingly insufficient food intake, refusing to receive professional care to quit the habit, mainly because he did not recognize it as disruptive.
The patient was admitted to hospital with symptoms suggestive of withdrawal, making it extremely difficult to control blood pressure levels. On the third day of admission to the acute care unit, fever peaks, blood pressure levels well below normal parameters, and compromised level of consciousness began to be evident.
Results
Blood tests were performed that, together with the clinical picture, suggested imminent septic shock, so critical care was contacted for transfer and stabilization. A germ of probable urinary etiology sensitive to a broad spectrum of antibiotics was isolated in blood cultures, and the medication of the detoxification process was progressively optimized. Once clinical stability was achieved at all levels, an inpatient cessation resource was managed, which the patient accepted and considered suitable for his complete recovery.
Conclusions
A holistic approach to the alcoholic patient is important, since serious problems of an organic nature often arise. This is why a multidisciplinary intervention is necessary, as well as a holistic approach to care, involving both classic pharmacology and assiduous long-term psychotherapeutic intervention.
A 28 year old patient will be presented. This paramilitary man was brought to the Emergency Room due to an autolytic attempt with Benzodiazepines, along with a mouth suture, in the context of a soon to be resolved problematic ankle osteosynthesis procedure. The patient claimed to be suffering pain, furthermore struggling due to the fact he could not be working due to his ankle issue. Language barrier was a problem during the interview.
Objectives
The objetives of this case is to try to explain the issues that may arise in patients with personality disorders in the context of an autolytic attempt
Methods
This patient will be presented, along with systematic bibliography review of the topic.
Results
The following results were extracted upon the attention given to this patient which was admitted to the Psychiatric Unit.
First of all, the mouth stitches were removed, along with a petition for toxicological analysis. The results gave positive for cannabis and benzodiazepines. The patient was also brought previously this year with another autolytic attempt, this time on cocaine consumption too. Furthermore, a thorough review was made of the other autolytic attempts, including those which happened in his country of origin. The patient has hundreds of small cuts among his arms, from previews cuts made in the past. Furthermore, subcutaneous wounds were auto inflicted in the ER, with a small blade.
Among the whole interview, it was clear he had a personality disorder, with high impulsivity levels and lack of control once the situation overflows.
We also tried to understand the outcome of suturing his mouth. The patient referred his acts of impulsiveness due to his overwhelming situation of both having no job at this moment and the pain he was suffering due to his ankle procedure.
The patient was admitted to our Unit due to the high risk he could repeat this act. Upon arrival, the same day he was admitted, the patient asked if he had to stay at the unit. When explaining the following already told event, furthermore insisting in the possibility of been evaluated by the Traumatology team, he proceeded to try and hang himself with his medical-hospital clothing.
The patient was treated with antipsychotics. Along with Lormetazepam at night. At the end of the hospitalization, and after been evaluated by the Psychiatrist of this Unit, the patient was also treated with Lithium due to its effectiveness in the treatment of autolytic attempts.
Conclusions
Personality disorders are one of the psychiatric pathologies that prevail with greater frequency in autolytic attempts 1. Additionally, it should be taken into account the possible ongoing consumption of psychoactive drugs that could also derive in psychopathological decompensation. On top of the following, the use of antipsychotic treatment is indicated for the managing of conduction altercations 2, besides Lithium being a great option in managing suicidal temptations 3.
Schizotypal personality is a condition suffered by 4% of the population. It is defined by presenting interpersonal, behavioral and perceptual features similar to the clinical features of psychotic disorders, such as schizophrenia, in less intensity and dysfunctionality, but at risk of reaching psychosis.
Objectives
Presentation of a clinical case about a patient with premorbid schizotypal personality traits presenting with an acute psychotic episode.
Methods
Literature review on association between schizotypal personality and psychosis.
Results
A 57-year-old woman with a history of adaptive disorder due to work problems 13 years ago, currently without psychopharmacological treatment, goes to the emergency room brought by the emergency services due to behavioral alteration. She reports that “her husband and son wanted to sexually abuse her”, so she had to run away from home and has been running through the streets of the town without clothes and barefoot.
Her husband relates attitude alterations and extravagant behaviors of years of evolution, such as going on diets of eating only bread for 40 days or talking about exoteric and religious subjects, as believing that the devil got inside her husband through a dental implant. He reports that these behaviors have been accentuated during the last month. She has also created a tarot website, and has even had discussions with several users. She is increasingly suspicious of him, has stopped talking to him and stays in his room all day long, with unmotivated laughter and soliloquies.
It was decided to admit him to Psychiatry and risperidone 4 mg was started. At the beginning, she was suspicious and reticent in the interview. As the days went by, communication improved, she showed a relaxed gesture and distanced herself from the delirious ideation, criticizing the episode.
Conclusions
In recent years, there has been increasing interest in understanding the association between schizotypy and serious mental disorder. Several theories understand schizotypy as a natural continuum of personality that reveals genetic vulnerability and that can lead to psychotic disorder when added to precipitating factors. Other theories define schizotypy as a “latent schizophrenia” where symptoms are contained and expressed in less intensity.
Around 20% evolves to paranoid schizophrenia or other serious mental disorders. It is complex to distinguish between those individuals in whom schizotypy is a prodrome and those in whom it is a stable personality trait. To date, studies applying early psychotherapeutic or pharmacological interventions have had insufficient and contradictory results, and the follow-up and treatment of these individuals could be a stress factor and a stigma. Some studies are looking for reliable markers of evolution to schizophrenia in order to establish adequate protocols for detention, follow-up and treatment.
Conversive disorder is characterised by the presence of one or more involuntary neurological symptoms that are not due to a clear medical pathology. On the other hand, consciously simulated illnesses fall into two diagnostic categories: factitious disorders and malingering, which are differentiated by both the motivation for the behaviour and the awareness of that motivation. Factitious disorder behaviours are motivated by an unconscious need to assume the sick role, whereas malingering behaviours are consciously driven to achieve external secondary gains.
Objectives
Study of the differences between conversion disorder and factitious disorder and their repercussions from a case of difficult diagnosis.
Methods
Bibliographic review of scientific literature based on a relevant clinical case.
Results
We present the case of a 14-year-old male patient. Adoptive parents. Studying in high school. Social difficulties since childhood. He comes to the emergency department on several occasions referring stereotyped movements and motor tics in the four extremities with left cervical lateralization. Increase of these symptoms in the last month, so it was decided to admit him to the pediatric hospital. After observation and study of the patient’s movements with normal complementary tests he should return home. The following day he returned to the emergency department after an episode of dizziness, mutism and emotional block. It was decided to admit him to Psychiatry for behavioral observation and differential diagnosis.
Conclusions
In the assessment of patients it is essential to make an appropriate diagnosis taking into account the patient’s symptomatology and the patient’s background and life context. Conversion disorder is the unintentional production of neurological symptom, whereas malingering and factitious disorder represent the voluntary production of symptoms with internal or external incentives. They have a close history and this has been frequently confounded. Practitioners are often confronted to medically unexplained symptoms; they represent almost 30% of neurologist’s consultation. The first challenge is to detect them, and recent studies have confirmed the importance of “positive” clinical bedside signs based on incoherence and discordance. Multidisciplinary therapy is recommended with behavioral cognitive therapy, antidepressant to treat frequent comorbid anxiety or depression, and physiotherapy. Factitious disorder and malingering should be clearly delineated from conversion disorder. Factitious disorder should be considered as a mental illness and more research on its physiopathology and treatment is needed, when malingering is a non-medical condition encountered in medico-legal cases.
Clozapine is an atypical antipsychotic synthesised in 1958. It was withdrawn from the market in the 1970s due to the appearance of agranulocytosis, but was reintroduced due to strong evidence of its efficacy and superiority over other antipsychotics in treatment-resistant schizophrenia.
Objectives
To describe the adequate response to clozapine in treatment-refractory psychosis.
Methods
Review of the scientific literature based on a relevant clinical case.
Results
A 16-year-old woman was admitted to a psychiatric inpatient unit for psychotic symptoms and behavioural disorders. She lives with her father and older sister; she has not been in contact with her mother, who lives in another country, for several years. She attends secondary school, with poor academic performance. Maternal diagnosis of schizophrenia. She started using cannabis two years ago, with a progressive increase up to 20 grams per week. He reports the onset of a feeling of strangeness a year ago, with progressive isolation in his room, referring to delirious ideation of harm towards classmates and people from his town, self-referentiality and delirious interpretations of religious mystical content (“God speaks to me through a dove”). He comments on the phenomenon of theft and thought-reading. Soliloquies and unmotivated laughter are observed.
Conclusions
Treatment was started with risperidone, progressively increasing the dose up to optimisation, without achieving a decrease in positive symptoms, but with the appearance of excessive sedation and sialorrhoea. It was combined with aripiprazole up to 20mg, maintained for a couple of weeks, without significant clinical improvement. Given the failure of two lines of therapy, it was decided to change to clozapine up to a dose of 75mg, with adequate tolerance and response, achieving a distancing of the delirious ideation. Regular haematological controls were performed, with no alterations in haemogram or troponins.
Lithium was the first mood stabilizer and today continues to be a first-line treatment in the treatment of bipolar disorder despite its adverse effects, which make it important to monitor blood levels and control kidney function.
Objectives
Presentation of a case of litium withdrawal and relapse in bipolar disorder. Literature review relating to the risk of relapse when lithium treatment is interrupted.
Methods
We present a clinical case of a patient who suffers a deterioration in renal function that requires the withdrawal of lithium and who consequently suffers a relapse. We conducted a bibliographic research of articles in Pubmed on this topic.
Results
A 49-year-old male, with a history of multiple admissions to UHB since the age of 18 with a diagnosis of bipolar disorder and treatment with lithium. Decompensations towards the manic pole have always been related to interruptions in lithium treatment. On several occasions when the patient was feeling well emotionally, he believed himself to be “cured” and abandoned the treatment, triggering a manic episode, showing verbal aggression, increased self-esteem and delusional ideation of harm. Remission was usually achieved with the reintroduction of lithium and the addition of high-dose quetiapine. Between episodes, constant overvalued ideas of economic scarcity seemed to persist, which were accentuated in the form of delusional ideas of ruin in depressive decompensations. After 7 years of stability, control analysis showed blood litemia of 2.2 mEq/L with deterioration of kidney function and generalized tremor was observed, without improvement after serum therapy. He was admitted for dialysis and lithium was suspended. Treatment with valproate was started and a consultation scheduled in a week to adjust the dose. The patient did not attend that consultation and was admitted three days later to Psychiatry Hospitalization showing a challenging attitude, evident dysphoric mood, accelerated speech, with derailments and echolalia. Delusional ideation of harm with auditory hallucinations. Insomnia and hyporexia. Chronic renal failure persisted.
Conclusions
Lithium is a very effective drug but with a narrow therapeutic range that requires adequate monitoring due to the possible consequences of its use at different organs and systems of the body. when lithium is found in the blood at toxic levels with deterioration of kidney function and glomerular filtration fails to recover, lithium treatment should be suspended. Sudden withdrawal of lithium significantly increases the risk of relapse due to rebound effect. More than 50% of patients experience a recurrence within 10 weeks of withdrawal.