Characterizing memory loss in patients with autoimmune limbic encephalitis hippocampal lesions.

Since the publication of Scoville and Milner's (1957) seminal paper, the precise functional role played by the hippocampus in support of human memory has been fiercely debated. For instance, the single question of whether the hippocampus plays a time-limited or an indelible role in the recollection of personal memories led to a deep and tenacious schism within the field. Similar polarizations arose between those who debated the precise nature of the role played by the hippocampus in support of semantic relative to episodic memories and in recall/recollection relative to familiarity-based recognition. At the epicenter of these divisions lies conflicting neuropsychological findings. These differences likely arise due to the consistent use of heterogeneous patient populations to adjudicate between these positions. Here we utilized traditional neuropsychological measures in a homogenous patient population with a highly discrete hippocampal lesion (i.e., VGKCC-Ab related autoimmune limbic encephalitis patients). We observed consistent impairment of recent episodic memories, a present but less striking impairment of remote episodic memories, preservation of personal semantic memory, and recall but not recognition memory deficits. We conclude that this increasingly well-characterized patient group may represent an important homogeneous population in which the functional role played by the hippocampus may be more precisely delineated.

Assisted dying: reflections on the psychological process.

This paper explores the question of assisted dying from both a legal and psychological perspective within the legal parameters in place at the time of writing of this paper. Links are made between Kohut's notion of an acceptance of the finiteness of existence and of transience as one of several indicators of the maturation and transformation of archaic narcissism, and Jung's notion of the readiness and ability to 'die with life' as the goal of the second half of life. The author raises awareness of the importance of the need for clarity with regard to these issues on the part of therapists who may be required to provide an evaluation of a patient's admissibility to a service of assisted dying.

Cet article explore le sujet de l'aide à la mort, à la fois du point de vue légal et psychologique, dans les paramètres légaux en place au moment de son écriture. L'article fait des liens entre la notion de Kohut - l'acceptation de l'aspect fini de l'existence et de son caractère éphémère comme l'un des indicateurs de la maturation et de la transformation du narcissisme archaïque - et l'idée de Jung selon laquelle le but de la seconde moitié de la vie est de développer sa capacité à « mourir avec la vie ¼. L'auteur attire l'attention sur l'importance du besoin de clarté concernant ces questions chez les thérapeutes auxquels on pourrait demander de fournir une évaluation de l'admissibilité d'un patient dans un service d'aide à la mort.

El presente trabajo explora el tema del acompañar el proceso de morir desde una perspectiva legal y psicológica en el marco de los parámetros legales existentes al momento de escribir el trabajo. Se plantean conexiones entre la noción de Kohut, de aceptación de la finitud de la existencia y la de transitoriedad como uno de los muchos indicadores de maduración y transformación del narcisismo primitivo, y la noción de Jung de disponibilidad y habilidad para 'morir con vida' como meta en la segunda mitad de la vida. El autor trae a la consciencia la importancia de la necesidad de claridad con respecto a estas cuestiones por parte de terapeutas quienes pueden ser requeridos para dar una evaluación sobre la admisibilidad de un paciente a un servicio de muerte asistida.

Este artigo explora a questão da morte assistida de uma perspectiva jurídica e psicológica dentro dos parâmetros legais em vigor no momento da redação deste artigo. São feitas ligações entre a noção de Kohut de aceitação da finitude da existência e da transitoriedade como um dos vários indicadores da maturação e transformação do narcisismo arcaico, e a noção de Jung da prontidão e capacidade de "morrer com vida" como o objetivo da segunda metade da vida. O autor conscientiza sobre a importância da necessidade de clareza em relação a essas questões por parte dos terapeutas que podem ser obrigados a fornecer uma avaliação da admissibilidade de um paciente a um serviço de morte assistida.

Friendship, loneliness and psychosocial functioning in children with traumatic brain injury.

OBJECTIVE: This study compares friendship quality, rates of loneliness and general psychosocial functioning in children who have sustained a traumatic brain injury (TBI) with non-injured controls. METHODS: A between-subjects design with 14 participants in the TBI group and 14 in the non-injured control group, aged between 7-13 years and matched for age, gender, receptive vocabulary and socio-economic status. Children completed measures of receptive vocabulary (BPVS II), friendship quality (FQQ-R) and loneliness (LSDS). The main caregiver was asked to assess social skills and social withdrawal (PIC-2) and general psychosocial and behavioural functioning (SDQ). RESULTS: Significant differences were not found on measures completed by children or on the PIC-2. On the SDQ, total difficulties were rated as much greater by caregivers in the TBI group (z = -2.6, p = 0.009) and these were mainly associated with sub-scales relating to emotional problems and hyperactivity. CONCLUSIONS: Whilst evidence for friendship problems was not found in children with TBI, evidence for emotional and behavioural difficulties that may lead to social vulnerabilities later in life were found. This indicates a need for prospective longitudinal research to explore the complex relationship between TBI and poorer social outcomes that may not become evident until adolescence.

Noncanonical vancomycin resistance cluster from Desulfitobacterium hafniense Y51.

The glycopeptide vancomycin is a drug of last resort for infection with gram-positive organisms, and three genes are vital to resistance: vanH, vanA, and vanX. These genes are found in a vanHAX cluster, which is conserved across pathogenic bacteria, glycopeptide antibiotic producers, and other environmental bacteria. The genome sequence of the anaerobic, gram-positive, dehalogenating bacterium Desulfitobacterium hafniense Y51 revealed a predicted vanA homolog; however, it exists in a vanAWK-murFX cluster, unlike those of other vancomycin-resistant organisms. Using purified recombinant VanA from D. hafniense Y51, we determined its substrate specificity and found it to have a 42-fold preference for D-lactate over D-alanine, confirming its activity as a D-Ala-D-Lac ligase and its annotation as VanA. Furthermore, we showed that D. hafniense Y51 is highly resistant to vancomycin, with a MIC for growth of 64 microg/ml. Finally, vanA(Dh) is expressed during growth in vancomycin, as demonstrated by reverse transcription-PCR. This finding represents a new glycopeptide antibiotic resistance gene cluster and expands the genetic diversity of resistance to this important class of antibiotic.

An analysis of orphan medicine expenditure in Europe: is it sustainable?

BACKGROUND: Orphan medicinal product (OMP) prices are considered by some to be a challenge to the sustainability of healthcare expenditure. These concerns are compounded by the increasing number of OMPs receiving marketing authorisation (MA) annually. The aim of this study was to explore the sustainability of OMP expenditure within the context of total European pharmaceutical expenditure. METHODS: Using historical IQVIA data, an analysis was conducted on total pharmaceutical and OMP expenditure in eight countries (using values / volumes) in the branded, non-branded and overall pharmaceutical market. Country level and aggregated data was considered for EU5 countries, Austria, Belgium and Ireland. Three key analyses were conducted: 1.The OMP share of total pharmaceutical expenditure was calculated from 2000 to 2017, to assess its evolution over time.2.The results of this analysis were compared with a 2011 forecast of OMP budget impact.3.The evolution of the total pharmaceutical market and its different segments (branded OMPs, non-OMP branded and unbranded) were assessed by estimating the compound annual growth rate (CAGR) and percentage of pharmaceutical expenditure for each market segment from 2010 to 2017. RESULTS: Across countries, OMP share of total pharmaceutical expenditure has increased each year since 2000, rising to 7.2% of total pharmaceutical expenditure in 2017. OMP expenditure has increased at a CAGR of 16% since 2010. The number of OMPs receiving MA each year showed a CAGR of 11% since 2001, four percentage points greater than the CAGR for all medicines receiving MA over the same period. OMP share of total pharmaceutical expenditure is higher than forecasted in 2011 due to slower than expected growth in the non-OMP market. OMP growth has been offset by reduced expenditure in the general market and increased use of generics and biosimilars. CONCLUSIONS: Relative spending on OMPs has increased over the last 20 years, but this has been largely compensated for within the current allocation of total pharmaceutical spending by flat expenditure for non-OMPs and increased volumes of (lower-priced) generics/biosimilars, reflecting a shift towards expenditure in higher cost, lower volume patient populations and a shift in drug development towards more specialised targeting of diseases.

Linking public health, housing, and indoor environmental policy: successes and challenges at local and federal agencies in the United States.

We describe the successes and challenges faced by federal and local government agencies in the United States as they have attempted in recent years to connect public and environmental health, housing, community development, and building design with environmental, housing, and building laws, codes, and policies. These policies can either contribute to or adversely affect human physical and mental health, with important implications for economic viability, research, policy development, and overall social stability and progress. Policy impediments include tension between housing affordability and health investment that causes inefficient cost-shifting, privacy issues, unclear statutory authority, and resulting gaps in responsibility for housing, indoor air, and the built environment. We contrast this with other environmental frameworks such as ambient air and water quality statutes where the concept of "shared commons" and the "polluter pays" is more robust. The U.S. experiences in childhood lead poisoning prevention, indoor air, and mold provide useful policy insights. Local programs can effectively build healthy homes capacity through local laws and housing codes. The experience of coordinating remediation for mold, asthma triggers, weatherization, and other healthy housing improvements in Cuyahoga County, Ohio, is highlighted. The U.S. experience shows that policymakers should adopt a prevention-oriented, comprehensive multi-disciplinary approach at all levels of government to prevent unhealthy buildings, houses, and communities.

The making of an analyst: from 'ideal' to 'good-enough'.

This paper addresses the issue of variances in training modalities and how this is linked to one's personal experience of training and to one's analytic lineage. The author, who bases his reflections on discussions held during the yearly directors of training meeting of the North American Jungian Societies, suggests that, while each institute aims to provide an 'ideal' training programme for its candidates, the philosophy underlying how this ideal is defined depends, in large part, on the theoretical and philosophical orientation of the founding fathers and mothers. This results in a form of analytic lineage that necessarily impacts on the form and content of the 'ideal' programme. Shadow issues related to analytic lineage in the admissions procedures, case consultation, exam committees and review committees are presented. Motivation for why we choose to train and reflections on what makes an analyst 'Jungian' are explored.

Genetic rescue increases fitness and aids rapid recovery of an endangered marsupial population.

Genetic rescue has now been attempted in several threatened species, but the contribution of genetics per se to any increase in population health can be hard to identify. Rescue is expected to be particularly useful when individuals are introduced into small isolated populations with low levels of genetic variation. Here we consider such a situation by documenting genetic rescue in the mountain pygmy possum, Burramys parvus. Rapid population recovery occurred in the target population after the introduction of a small number of males from a large genetically diverged population. Initial hybrid fitness was more than two-fold higher than non-hybrids; hybrid animals had a larger body size, and female hybrids produced more pouch young and lived longer. Genetic rescue likely contributed to the largest population size ever being recorded at this site. These data point to genetic rescue as being a potentially useful option for the recovery of small threatened populations.

The effects of acute tryptophan depletion on neuropsychological function.

Serotonin (5-HT, 5-hydroxytryptamine) may have an important role in the maintenance of normal neuropsychological functioning. The method of acute tryptophan depletion (ATD) provides a pharmacological challenge by which central 5-HT levels can be temporarily decreased and effects on learning, memory and mood examined. Twenty healthy male volunteers were recruited to take part in this within-subject, double-blind, crossover study. Neuropsychological function was evaluated 4-6 h after ingestion of a control or 52 g tryptophan (TRP) depleting amino-acid drink. ATD significantly lowered levels of plasma total and free TRP (p < 0.001), but this did not affect mood or performance on tests of verbal and visuo-spatial learning and memory, attention or executive function. These results contradict previous findings; however, the degree of disruption of central 5-HT levels resulting from the use of the 52 g amino-acid protocol may be an important factor in explaining the lack of effect. By utilizing more specific probes of individual 5-HT receptor subtypes, future studies can fully explore the role of 5-HT in neuropsychological functioning and may elucidate the factors determining vulnerability to the effects of serotonergic dysfunction.

Air pollution and the demand for hospital services: a review.

Time-series studies published since 1993 on the association between short-term changes in air quality and use of hospital services, including both inpatient and emergency room use, are reviewed. The use of nonparametric analysis, often incorporating generalized additive models (GAMs), has increased greatly since the early 1990s. There have also been three major multi-city studies, which together analyzed data from well over 100 cities in Europe and North America. Various air pollutants, especially ozone (O(3)), particulate matter (PM), nitrogen dioxide (NO(2)) and sulfur dioxide (SO(2)), were generally found to be significantly associated with increased use of hospital services. Ozone tends to have stronger effects in the summer during periods of higher concentrations. Several studies revealed synergistic effects between pollutants such as PM and SO(2). Overall, short-term exposure to air pollutants is found to be an important predictor of increased hospital and emergency room use around the world.

A personality-based taxonomy of sexually abusive adolescents derived from the Millon Adolescent Clinical Inventory (MACI).

A personality-based taxonomy of an out-patient sample of 112 sexually abusive adolescents is described. Five subgroups were derived from cluster analytic procedures applied to Personality Patterns scales scores from the Millon Adolescent Clinical Inventory (MACI), and were named: Normal, Antisocial, Submissive, Dysthymic/Inhibited, and Dysthymic/Negativistic. The groups were also found to be differentiated on the psychopathology scales of the MACI. The results of the study provide evidence of the heterogeneity of adolescent sexual abusers in both personality characteristics and psychopathology. Comparison of groups differentiated on the basis of victim characteristics did not indicate a relationship between personality and sexual offence.

Exploring the role of auditory analysis in atypical compared to typical language development.

The relationship between auditory processing and language skills has been debated for decades. Previous findings have been inconsistent, both in typically developing and impaired subjects, including those with dyslexia or specific language impairment. Whether correlations between auditory and language skills are consistent between different populations has hardly been addressed at all. The present work presents an exploratory approach of testing for patterns of correlations in a range of measures of auditory processing. In a recent study, we reported findings from a large cohort of eleven-year olds on a range of auditory measures and the data supported a specific role for the processing of short sequences in pitch and time in typical language development. Here we tested whether a group of individuals with dyslexic traits (DT group; n = 28) from the same year group would show the same pattern of correlations between auditory and language skills as the typically developing group (TD group; n = 173). Regarding the raw scores, the DT group showed a significantly poorer performance on the language but not the auditory measures, including measures of pitch, time and rhythm, and timbre (modulation). In terms of correlations, there was a tendency to decrease in correlations between short-sequence processing and language skills, contrasted by a significant increase in correlation for basic, single-sound processing, in particular in the domain of modulation. The data support the notion that the fundamental relationship between auditory and language skills might differ in atypical compared to typical language development, with the implication that merging data or drawing inference between populations might be problematic. Further examination of the relationship between both basic sound feature analysis and music-like sound analysis and language skills in impaired populations might allow the development of appropriate training strategies. These might include types of musical training to augment language skills via their common bases in sound sequence analysis.

White matter correlates of cognitive dysfunction after mild traumatic brain injury.

OBJECTIVE: To relate neurophysiologic changes after mild/moderate traumatic brain injury to cognitive deficit in a longitudinal diffusion tensor imaging investigation. METHODS: Fifty-three patients were scanned an average of 6 days postinjury (range = 1-14 days). Twenty-three patients were rescanned 1 year later. Thirty-three matched control subjects were recruited. At the time of scanning, participants completed cognitive testing. Tract-Based Spatial Statistics was used to conduct voxel-wise analysis on diffusion changes and to explore regressions between diffusion metrics and cognitive performance. RESULTS: Acutely, increased axial diffusivity drove a fractional anisotropy (FA) increase, while decreased radial diffusivity drove a negative regression between FA and Verbal Letter Fluency across widespread white matter regions, but particularly in the ascending fibers of the corpus callosum. Raised FA is hypothesized to be caused by astrogliosis and compaction of axonal neurofilament, which would also affect cognitive functioning. Chronically, FA was decreased, suggesting myelin sheath disintegration, but still regressed negatively with Verbal Letter Fluency in the anterior forceps. CONCLUSIONS: Acute mild/moderate traumatic brain injury is characterized by increased tissue FA, which represents a clear neurobiological link between cognitive dysfunction and white matter injury after mild/moderate injury.

15-year follow-up of recurrent "hypoglycemia" in preterm infants.

BACKGROUND: Observational study of 543 infants who weighed <1850 g, published in 1988 reported seriously impaired motor and cognitive development at 18 months in those with recurrent, asymptomatic hypoglycemia (plasma glucose level ≤2.5 mmol/L on ≥3 days). No study has yet replicated this observation. AIM: To quantify disability in a similar cohort of children followed up throughout childhood. POPULATION: All children born at <32 weeks' gestation in the north of England in 1990-1991 and had laboratory blood glucose levels measured daily for the first 10 days of life. RESULTS: Forty-seven index children of the 566 who survived to 2 years had a blood glucose level of ≤2.5 mmol/L on ≥3 days. All of these children and hypoglycemia-free controls, matched for hospital of care, gestation, and birth weight, were assessed at age 2. No differences in developmental progress or physical disability were detected. The families were seen again when the children were 15 years old, and 38 of the index children (81%) and matched controls agreed to detailed psychometric assessment. Findings in the 2 groups were nearly identical (mean full-scale IQ: 80.7 vs 81.2). Findings in the 21 children with a level of ≤2.5 mmol/L on ≥4 days, 7 children with a level this low on 5 days, and 11 children with a level of <2.0 mmol/L on 3 different days did not alter these conclusions. CONCLUSIONS: This study found no evidence to support the belief that recurrent low blood glucose levels (≤2.5 mmol/L) in the first 10 days of life usually pose a hazard to preterm infants.