The brief executive language screen: sensitivity and specificity in acute to early sub-acute stroke.

INTRODUCTION: Propositional language and underlying executive functions can be impaired post-stroke and affect communication and quality of life. Current stroke screening tools are largely tailored to patients with aphasia, being either non-verbal or focussed on core language skills such as naming and repetition. The Brief Executive Language Screening Test (BELS) is a newly developed cognitive screening tool that assesses memory, oral apraxia, core language, as well as propositional language and associated executive functions that can be impacted and overlooked in stroke patients without aphasia. This study examines BELS sensitivity and specificity, and performance in acute to early sub-acute stroke relative to controls. METHOD: Cross-sectional BELS data from 88 acute left and right hemisphere stroke patients (within 7 weeks of stroke) and 116 age-matched healthy controls were compared using independent samples t-tests. ROC Curve Analysis was performed to determine a cutoff score for the BELS. RESULTS: Left and right stroke patients were reduced on all propositional language subtests, and executive function subtests of inhibition, strategy, and selection. Differences were also observed for Oral Apraxia, Naming, and Memory. By contrast, Word Comprehension and Repetition, and Sentence Completion Initiation (after corrections applied) did not differ between groups. A total BELS score of 79.25/100 was highly sensitive (.89) and specific (.89) when classifying stroke patients and healthy controls. CONCLUSION: The BELS is brief, sensitive, suitable for bedside administration, and can aid in detection and rehabilitation of subtle executive language impairments. This in turn will help improve relationships and quality of life post-stroke.

Hayling and stroop tests tap dissociable deficits and network-level neural correlates.

Although many executive function screens have been developed, it is not yet clear whether these assessments are equally effective in detecting post-stroke deficits of initiation and inhibition. This study presents a comparative analysis of the Stroop and Hayling tests aiming to evaluate whether these tests measure the same underlying cognitive functions and to identify the neural correlates of the deficits detected by both tasks. Sixty six stroke survivors and 70 healthy ageing controls completed the Hayling and Stroop tests. Stroke patients were found to exhibit qualitative performance differences across analogous Stroop and Hayling Test metrics intended to tap initiation and inhibition. The Stroop test was found to have high specificity to abnormal performance, but low sensitivity relative to the Hayling Test. Minimal overlap was present between the network-level correlates of analogous Stroop and Hayling Test metrics. Hayling Task strategy use metrics were significantly associated with distinct patterns of disconnection in stroke survivors, providing novel insight into the neural correlates of fine-grained behavioural patterns. Overall, these findings strongly suggest that the functions tapped by the Stroop and Hayling Test are both behaviourally and anatomically dissociable. The Hayling Test was found to offer improved sensitivity and detail relative to the Stroop test. This novel demonstration of the Hayling Test within the stroke population suggests that this task represents an effective measure for quantifying post-stroke initiation and inhibition deficits.

Comparison of three-weekly and six-weekly pembrolizumab United Kingdom prescribing practice for advanced and resected melanoma.

BACKGROUND: Pembrolizumab is approved for the treatment of advanced and resected melanoma and was originally licensed as a three-weekly infusion (Q3W). In April 2019, a six-weekly infusion schedule (Q6W) was also approved. We retrospectively reviewed pembrolizumab prescribing for patients with melanoma across multiple United Kingdom (UK) centres to compare the safety and efficacy of Q6W with Q3W in real-world clinical practice. METHODS: Case notes for melanoma patients treated with pembrolizumab between April 2019 and August 2020 at eight UK centres were reviewed. Prespecified baseline characteristics of the Q3W and Q6W cohorts were compared, as well as toxicity and efficacy outcomes. Prescribers were surveyed about their prescribing practice. RESULTS: Two hundred seventy-seven patients were included: 116 commenced Q3W and 161 commenced Q6W pembrolizumab. The proportion of Q6W prescriptions varied by the centre (range 32-88%). Patient factors associated with an increased likelihood of receiving Q3W over Q6W were preexisting autoimmune comorbidity (odds ratio [OR] 0.33; 95% confidence interval [CI] 0.12-0.82) and treatment for advanced (versus resected) disease (OR 0.54; 95%CI 0.33-0.90). Toxicity outcomes were broadly similar for Q6W and Q3W: 14.9% versus 15.5% ≥ grade 3 Common Terminology Criteria for Adverse Events. Estimated 12-month recurrence-free survival for adjuvantly treated patients was 78.9% for Q6W and 74.2% for Q3W (hazard ratio [HR] 0.93; 95%CI 0.50-1.73). Estimated 12-month progression-free survival for advanced patients was 41.8% for Q6W and 55.9% for Q3W (HR 1.21, 95%CI 0.67-2.18). CONCLUSIONS: Q6W is an appropriate option for administering pembrolizumab, given the opportunity to reduce the health service resource burden.

Enhanced semantic memory in a case of highly superior autobiographical memory.

Highly superior autobiographical memory (HSAM) is characterised by the ability to recall personal events, dates, and news events from long-term memory with profound detail and accuracy. Anecdotes from these individuals suggest that retrieval of rich autobiographical detail is automatic, and often intrusive rather than effortful. We created two novel experiments to objectively verify whether retrieval of information reflects serial or parallel processing in a case of HSAM (R.S.), who has a self-reported superior memory for two sources of personally relevant information: (a) the ability to name days of the week for any given calendar date since the year 2000; and (b) the ability to remember the entire text, practically word-for-word, of the seven Harry Potter books. RS and 10 age-matched controls, who were also aficionados of the Harry Potter series, were presented with pairs of calendar dates or sentences and asked, "Which date came earlier in the week?" or "Which sentence came earlier in the book?" Items within a pair varied in the proximity to one another in time. RS correctly identified earlier calendar dates and sentences with near perfect accuracy, and her reaction time was not impacted by the temporal distance between items. Controls were unable to identify earlier calendar dates and their accuracy and reaction time was dependent on the temporal distance of items. Structural magnetic resonance imaging (MRI) comparing RS with a normative dataset found no significant differences in any memory-related brain regions. Our findings suggest that HSAM memory retrieval for stored information largely reflects parallel processing, rather than a temporal-based system. We also discovered that RS has superior memory for semantic information, boosted by reportedly attaching autobiographical memories to these details. This unusual HSAM phenomenon may hold further clues to creating strong and lasting memories, which appear to be uniquely rich in detail.

Investigating the role of future thinking in a case of highly superior autobiographical memory.

Highly superior autobiographical memory (HSAM) is characterised by a profound ability to recall personal experiences from long-term memory with extremely high detail and accuracy. Since the first documented case of HSAM in 2006, studies have demonstrated the apparent automatic and effortless retrieval of autobiographical memories, despite their Average performance on laboratory and neuropsychological tests of episodic memory. It remains unclear, however, if their ability to imagine future-oriented scenarios is also superior, a process that is known to rely heavily on our capacity to remember the past. Here we investigate autobiographical memory and future thinking in a case of HSAM. We report RS who endorses re-experiencing a constant influx of memories from almost every day of her life since early adolescence. RS's performance on tasks of autobiographical memory, episodic future thinking, and future-oriented scene construction was contrasted with six age- and sex-matched healthy control participants. Recollections of past autobiographical events were episodically richer in RS, but only when personal relevance of the event was highly constrained (i.e., cued by a single word and within a time limit). In addition, while imagination of plausible future events was significantly richer in episodic detail, construction of future-oriented narrative scenes was unremarkable. Our study is the first to investigate future thinking in HSAM. These individuals may engage in superior imagination of future scenarios, but only when these scenarios can be easily tied to their own personal narrative.

Females adjust maternal hormone concentration in eggs according to male condition in a burying beetle.

In birds and other vertebrates, there is good evidence that females adjust the allocation of hormones in their eggs in response to prenatal environmental conditions, such as food availability or male phenotype, with profound consequences for life history traits of offspring. In insects, there is also evidence that females deposit juvenile hormones (JH) and ecdysteroids (ESH) in their eggs, hormones that play a key role in regulating offspring growth and metamorphosis. However, it is unclear whether females adjust their hormonal deposition in eggs in response to prenatal environmental conditions. Here we address this gap by conducting an experiment on the burying beetle Nicrophorus vespilloides, in which we manipulated the presence of the male parent and the size of the carcass used for breeding at the time of laying. We also tested for effects of the condition (i.e., body mass) of the parents. We then recorded subsequent effects on JH and ESH concentrations in the eggs. We found no evidence for an effect of these prenatal environmental conditions (male presence and carcass size) on hormonal concentration in the eggs. However, we found that females reduced their deposition of JH when mated with heavier males. This finding is consistent with negative differential allocation of maternal hormones in response to variation in the body mass of the male parent. We encourage further work to investigate the role of maternally derived hormones in insect eggs.

Neural dynamics of the attentional blink revealed by encoding orientation selectivity during rapid visual presentation.

The human brain is inherently limited in the information it can make consciously accessible. When people monitor a rapid stream of visual items for two targets, they typically fail to see the second target if it occurs within 200-500 ms of the first, a phenomenon called the attentional blink (AB). The neural basis for the AB is poorly understood, partly because conventional neuroimaging techniques cannot resolve visual events displayed close together in time. Here we introduce an approach that characterises the precise effect of the AB on behaviour and neural activity. We employ multivariate encoding analyses to extract feature-selective information carried by randomly-oriented gratings. We show that feature selectivity is enhanced for correctly reported targets and suppressed when the same items are missed, whereas irrelevant distractor items are unaffected. The findings suggest that the AB involves both short- and long-range neural interactions between visual representations competing for access to consciousness.

Differential effects of offspring and maternal inbreeding on egg laying and offspring performance in the burying beetle Nicrophorus vespilloides.

We investigate the effect of offspring and maternal inbreeding on maternal and offspring traits associated with early offspring fitness in the burying beetle Nicrophorus vespilloides. We conducted two experiments. In the first experiment, we manipulated maternal inbreeding only (keeping offspring outbred) by generating mothers that were outbred, moderately inbred or highly inbred. Meanwhile, in the second experiment, we manipulated offspring inbreeding only (keeping females outbred) by generating offspring that were outbred, moderately inbred or highly inbred. In both experiments, we monitored subsequent effects on breeding success (number of larvae), maternal traits (clutch size, delay until laying, laying skew, laying spread and egg size) and offspring traits (hatching success, larval survival, duration of larval development and average larval mass). Maternal inbreeding reduced breeding success, and this effect was mediated through lower hatching success and greater larval mortality. Furthermore, inbred mothers produced clutches where egg laying was less skewed towards the early part of laying than outbred females. This reduction in the skew in egg laying is beneficial for larval survival, suggesting that inbred females adjusted their laying patterns facultatively, thereby partially compensating for the detrimental effects of maternal inbreeding on offspring. Finally, we found evidence of a nonlinear effect of offspring inbreeding coefficient on number of larvae dispersing. Offspring inbreeding affected larval survival and larval development time but also unexpectedly affected maternal traits (clutch size and delay until laying), suggesting that females adjust clutch size and the delay until laying in response to being related to their mate.

Closing the gaps: the impact of inpatient detoxification and continuity of care on client outcomes.

Inpatient detoxification is a critical element of the continuum of care for chemically dependent individuals, especially for those unable to establish sobriety on an outpatient basis. This study evaluated the impact of one such detoxification program on client outcomes during the year after detoxification. The program was a public/private partnership between Ventura County, California, and Tarzana Treatment Center in Los Angeles. Before admission, applicants agreed to enroll in treatment after detoxification. Clients were contacted at one month post-admission and quarterly thereafter for one year to collect data, corroborated by county records, on treatment and outcome variables. The sample included 117 consecutive admissions between July 2007 and June 2009. Detoxification completion rates and follow-up treatment enrollment rates were substantial: 85% of the sample completed detoxification; 71% enrolled in treatment afterward. Client outcomes were positive, particularly for those enrolled in followup treatment: compared to clients not completing detoxification, and to client functioning in the year before admission, sobriety and employment rates increased, and rates of homelessness, arrests and days incarcerated decreased. The study concludes that public investment in inpatient detoxification services and aftercare is an effective means to decrease both individual and societal costs of addiction.