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Historically, the multiple uses of cannabis as a medicine, food, and for recreational purposes as a psychoactive drug span several centuries. The various components of the plant (i.e., seeds, roots, leaves and flowers) have been utilized to alleviate symptoms of inflammation and pain (e.g., osteoarthritis, rheumatoid arthritis), mood disorders such as anxiety, and intestinal problems such as nausea, vomiting, abdominal pain and diarrhea. It has been established that the intestinal microbiota progresses neurological, endocrine, and immunological network effects through the gut–microbiota–brain axis, serving as a bilateral communication pathway between the central and enteric nervous systems. An expanding body of clinical evidence emphasizes that the endocannabinoid system has a fundamental connection in regulating immune responses. This is exemplified by its pivotal role in intestinal metabolic and immunity equilibrium and intestinal barrier integrity. This neuromodulator system responds to internal and external environmental signals while also serving as a homeostatic effector system, participating in a reciprocal association with the intestinal microbiota. We advance an exogenous cannabinoid–intestinal microbiota–endocannabinoid system axis potentiated by the intestinal microbiome and medicinal cannabinoids supporting the mechanism of action of the endocannabinoid system. An integrative medicine model of patient care is advanced that may provide patients with beneficial health outcomes when prescribed medicinal cannabis. [ABSTRACT FROM AUTHOR]

Background: Children with developmental language disorder (DLD) experience higher levels of peer victimization than their peers. However, it is not known if such associations reflect genetic and environmental confounding. We used a co‐twin control design to investigate the association of language difficulties (DLD and separately poor pragmatic language) with peer victimization and compare the developmental trajectories of peer victimization across adolescence for those with and without language difficulties. Methods: Participants were 3,400 pairs of twins in the Twins Early Development Study (TEDS), a UK‐based population birth cohort. Language abilities were assessed via online tests at age 11 and peer victimization was self‐reported at ages 11, 14 and 16. Language difficulties were defined as language abilities at least −1.25 SD below the mean of the TEDS sample. We performed linear regressions and latent growth curve modeling at a population level and within monozygotic and same‐sex dizygotic twin pairs. Results: At population level, youth with DLD experienced higher levels of peer victimization at ages 11 (β = 0.27, 95% Confidence Interval (CI) 0.20–0.35), 14 (β = 0.15, 95% CI 0.03–0.27) and 16 (β = 0.17, 95% CI 0.03–0.32) and a sharper decline in peer victimization between ages 11 and 16 compared to their peers without DLD. The associations between DLD and peer victimization were reduced in strength and not statistically significant in within‐twin models. Moreover, there was no difference in the rate of change in peer victimization between twin pairs discordant for DLD. Results were similar for the association of poor pragmatic language with peer victimization. Conclusions: Associations between language difficulties (DLD and separately, poor pragmatic language) and peer victimization were confounded by genetic and shared environmental factors. Identifying specific factors underlying these associations is important for guiding future work to reduce peer victimization among adolescents with language difficulties. [ABSTRACT FROM AUTHOR]

AbstractObjective: Mental health of college students is a matter of concern, and counseling centers have experienced a surge in demand and strain on capacity to provide services. This study explored the efficacy of a novel, nature-informed stress management curriculum entitled The Ecology of Resilience delivered via a for-credit general education course. The goals were a more favorable perception of stress and increased sense of bouncing back from stress (resilience). Participants: One hundred fifty-seven junior- and senior-level undergraduates participated in a project spanning three semesters from January 2022 to April 2023. Methods: The Perceived Stress Scale (PSS) and Brief Resilience Scale (BRS) were employed in a pretest/post-test arrangement. Results: PSS scores decreased significantly and BRS scores increased significantly for students enrolled in the course versus a control group. Conclusions: Curricula like the Ecology of Resilience, presented within the contexts of for-credit academic courses, are viable options for addressing student mental health. [ABSTRACT FROM AUTHOR]

This paper presents a novel approach to teaching how vaccines work in the body, and introduces a community outreach project and activity we piloted with youth. Our Nuestra Ciencia program addresses scientific misconceptions among bilingual elementary school children in engaging and scientifically accurate ways. Utilizing analogies and storytelling, one of our lessons simplifies the complex microbiology concept of the mechanism of action of vaccines. We underscore the issue with conveying this concept through accurate visuals, supported by our research that revealed that less than 1% of cartoons available online accurately depict how vaccines work. The analogy we developed and showcase in this paper employs relatable characters: the virus as a robber, the immune system as a superhero, and the vaccine as a "most wanted" poster. The activities include a skit and storyboard session, enabling students to act out the analogy and create their own imaginative scenarios. By targeting young learners, this lesson aims to prevent long-standing misconceptions and empower future generations to make informed decisions about vaccination. Nuestra Ciencia offers a promising model for combating vaccine hesitancy and promoting public health through effective science communication. [ABSTRACT FROM AUTHOR]

While recent scholarship has clarified the spelling of the little-known Old Assyrian nasbītum rite, formerly glossed as naspittum , its etymology and social context have remained obscure. This paper suggests the elusive rite has its etymology in the OA verb sabā'um , "to brew/draw beer," and refers to the act of libation. While the textual evidence for nasbītum is currently limited, an analysis of the rite as it occurs in the OA corpus suggests that nasbītum was the OA term for the care and feeding of the spirits of the dead, analogous to the better-known Old Babylonian kispum. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is a parasitic disease caused by trematodes of the genus Schistosoma. The intravascular worms acquire the nutrients necessary for their survival from host blood. Since all animals are auxotrophic for riboflavin (vitamin B2), schistosomes too must import it to survive. Riboflavin is an essential component of the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD); these support key functions of dozens of flavoenzymes. Methods: Here, using a combination of metabolomics, enzyme kinetics and in silico molecular analysis, we focus on the biochemistry of riboflavin and its metabolites in Schistosoma mansoni (Sm). Results: We show that when schistosomes are incubated in murine plasma, levels of FAD decrease over time while levels of FMN increase. We show that live schistosomes cleave exogenous FAD to generate FMN and this ability is significantly blocked when expression of the surface nucleotide pyrophosphatase/phosphodiesterase ectoenzyme SmNPP5 is suppressed using RNAi. Recombinant SmNPP5 cleaves FAD with a Km of 178 ± 5.9 µM and Kcat/Km of 324,734 ± 36,347 M− 1.S− 1. The FAD-dependent enzyme IL-4I1 drives the oxidative deamination of phenylalanine to produce phenylpyruvate and H2O2. Since schistosomes are damaged by H2O2, we determined if SmNPP5 could impede H2O2 production by blocking IL-4I1 action in vitro. We found that this was not the case; covalently bound FAD on IL-4I1 appears inaccessible to SmNPP5. We also report that live schistosomes can cleave exogenous FMN to generate riboflavin and this ability is significantly impeded when expression of a second surface ectoenzyme (alkaline phosphatase, SmAP) is suppressed. Recombinant SmAP cleaves FMN with a Km of 3.82 ± 0.58 mM and Kcat/Km of 1393 ± 347 M− 1.S− 1. Conclusions: The sequential hydrolysis of FAD by tegumental ecto-enzymes SmNPP5 and SmAP can generate free vitamin B2 around the worms from where it can be conveniently imported by the recently described schistosome riboflavin transporter SmaRT. Finally, we identified in silico schistosome homologs of enzymes that are involved in intracellular vitamin B2 metabolism. These are riboflavin kinase (SmRFK) as well as FAD synthase (SmFADS); cDNAs encoding these two enzymes were cloned and sequenced. SmRFK is predicted to convert riboflavin to FMN while SmFADS could further act on FMN to regenerate FAD in order to facilitate robust vitamin B2-dependent metabolism in schistosomes. [ABSTRACT FROM AUTHOR]

We start a systematic analysis of the first-order model theory of free lattices. Firstly, we prove that the free lattices of finite rank are not positively indistinguishable, as there is a positive ∃ ∀ {\exists\forall} -sentence true in 퐅 3 {\mathbf{F}_{3}} and false in 퐅 4 {\mathbf{F}_{4}} . Secondly, we show that every model of Th ⁢ ( 퐅 n ) {\mathrm{Th}(\mathbf{F}_{n})} admits a canonical homomorphism into the profinite-bounded completion 퐇 n {\mathbf{H}_{n}} of 퐅 n {\mathbf{F}_{n}} . Thirdly, we show that 퐇 n {\mathbf{H}_{n}} is isomorphic to the Dedekind–MacNeille completion of 퐅 n {\mathbf{F}_{n}} , and that 퐇 n {\mathbf{H}_{n}} is not positively elementarily equivalent to 퐅 n {\mathbf{F}_{n}} , as there is a positive ∀ ∃ {\forall\exists} -sentence true in 퐇 n {\mathbf{H}_{n}} and false in 퐅 n {\mathbf{F}_{n}} . Finally, we show that DM ⁢ ( 퐅 n ) {\mathrm{DM}(\mathbf{F}_{n})} is a retract of Id ⁢ ( 퐅 n ) {\mathrm{Id}(\mathbf{F}_{n})} and that for any lattice 퐊 {\mathbf{K}} which satisfies Whitman’s condition ( W ) {\mathrm{(W)}} and which is generated by join prime elements, the three lattices 퐊 {\mathbf{K}} , DM ⁢ ( 퐊 ) {\mathrm{DM}(\mathbf{K})} , and Id ⁢ ( 퐊 ) {\mathrm{Id}(\mathbf{K})} all share the same positive universal first-order theory. [ABSTRACT FROM AUTHOR]

Background: Recent observational studies suggest higher blood pressure (BP) variability (BPV) is associated with Alzheimer's disease (AD) biomarkers amyloid-beta (Aβ) and tau. Less is known about relationships in interventional cohorts with strictly controlled mean BP levels. Objective: Investigate the longitudinal relationship between BPV and change in plasma AD biomarkers under standard versus intensive BP treatment. Methods: In this post hoc analysis of the SPRINT trial, 457 participants (n = 206 in standard group, n = 251 in intensive group) underwent repeated BP measurement between baseline and 12-months follow-up, and venipuncture at baseline and median (IQR) 3.5 (3.0–4.0) years later to determine plasma AD biomarkers total tau and Aβ1–42:Aβ1–40 ratio. BPV was calculated as tertiles of variability independent of mean. Linear mixed models investigated the effect of BPV×time on AD biomarker levels. Results: Higher BPV was associated with increased levels of total tau in the standard group (β [95% CI] 1st versus 3rd tertiles of BPV: 0.21 [0.02, 0.41], p = 0.035), but not in the intensive group (β [95% CI] 1st versus 3rd tertiles of BPV: −0.02 [−0.19, 0.16], p = 0.843). BPV was not associated with Aβ 1–42:Aβ 1–40 ratio in either group. Mean BP was not associated with biomarkers. Conclusions: Higher BPV was associated with increased plasma total tau under standard BP treatment. Findings add new evidence to prior observational work linking BPV to AD pathophysiology and suggest that, despite strict control of mean BP, BPV remains a risk for pathophysiological change underlying risk for AD. [ABSTRACT FROM AUTHOR]

While recent scholarship has clarified the spelling of the little-known Old Assyrian nasbītum rite, formerly glossed as naspittum , its etymology and social context have remained obscure. This paper suggests the elusive rite has its etymology in the OA verb sabā'um , "to brew/draw beer," and refers to the act of libation. While the textual evidence for nasbītum is currently limited, an analysis of the rite as it occurs in the OA corpus suggests that nasbītum was the OA term for the care and feeding of the spirits of the dead, analogous to the better-known Old Babylonian kispum. [ABSTRACT FROM AUTHOR]

Goal: Employee assistance programs (EAPs) have been evolving since they first became prevalent in the 1970s. The important counseling component of EAPs is sometimes lost in discussions about what they do, with many EAPs marketing a broad portfolio of services such as childcare, elder care, legal referral, and other concierge services rather than counseling. The objective of this study was to examine outcomes for the EAP of one organization (Mayo Clinic), compare them to outcomes reported in the literature, and gain insights to help all healthcare organizations best support their employees. Methods: Consistent with customary EAP practice, data for this study was collected through an anonymous survey link distributed by e-mail to users of individual counseling as well as users of organizational consulting services such as advising leaders and supervisors and leading educational sessions. Principal Findings: All (n = 82) individual counseling respondents indicated they would recommend the EAP, none reported worse symptoms, 90% decreased their stress levels, 92% reduced their feelings of anxiety, 88% enjoyed an overall improvement in mood, and 95% developed new skills. If their concern was work-related, 96% agreed the counselor understood the work culture and was able to provide helpful guidance; of the clients who were feeling burned out, 86% agreed they gained strategies to reduce its symptoms. Thematic analysis of individual counseling services indicated that participants highly valued their counselors. Regarding organizational consulting services, respondents (n = 50) indicated EAP services increased their confidence as leaders, supported their work, and provided tangible guidance. They appreciated having an internal EAP counselor. Thematic analysis of organizational consulting services indicated that EAP supported leaders by listening, coaching, and empowering them to normalize issues. Practical Applications: EAPs have evolved into distinct internal, external, and hybrid internal-external models. Internal model counselors are company employees with inside knowledge of company culture, external EAP model counselors are contracted outside of the company, and hybrid models combine a small cadre of internal counselors with the support of outside contractors. Regardless of the model, EAP counselors must collaborate with internal stakeholders, notably the human resources department, to efficiently identify and troubleshoot employee relational issues and allow for customized initiatives to improve mental health. Based upon these findings and the authors' direct experiences with EAP providers, components of an ideal EAP are outlined to show how EAPs can best support employees. Healthcare leaders seeking to add EAP services are advised to focus on offerings that are custom fit to the organization. [ABSTRACT FROM AUTHOR]

In Transfer Learning (TL) a model that is trained on one problem is used to simplify the learning process on a second problem. TL has achieved impressive results for Deep Learning, but has been scarcely studied in genetic programming (GP). Moreover, predicting when, or why, TL might succeed is an open question. This work presents an approach to determine when two problems might be compatible for TL. This question is studied for TL with GP for the first time, focusing on multiclass classification. Using a set of reference problems, each problem pair is categorized into one of two groups. TL compatible problems are problem pairs where TL was successful, while TL non-compatible problems are problem pairs where TL was unsuccessful, relative to baseline methods. DeepInsight is used to extract a 2D projection of the feature space of each problem, and a similarity measure is computed by registering the feature space representation of both problems. Results show that it is possible to distinguish between both groups with statistical significant results. The proposal does not require model training or inference, and can be applied to problems from different domains, with a different a number of samples, features and classes. [ABSTRACT FROM AUTHOR]

Background: Blood pressure variability (BPV) is associated with cognitive decline and Alzheimer's disease (AD), but relationships with AD risk gene apolipoprotein (APOE) ɛ4 remain understudied. Objective: Examined the longitudinal relationship between BPV and cognitive change in APOE ɛ4 carriers and APOE ɛ3 homozygotes. Methods: 1,194 Alzheimer's Disease Neuroimaging Initiative participants (554 APOE ɛ4 carriers) underwent 3-4 blood pressure measurements between study baseline and 12-month follow-up. Visit-to-visit BPV was calculated as variability independent of mean over these 12 months. Participants subsequently underwent ≥1 neuropsychological exam at 12-month follow-up or later (up to 156 months later). Composite scores for the domains of memory, language, executive function, and visuospatial abilities were determined. Linear mixed models examined the 3-way interaction of BPV×APOE ɛ4 carrier status x time predicting change in composite scores. Results: Higher systolic BPV predicted greater decline in memory (+1 SD increase of BPV: β= –0.001, p < 0.001) and language (β= –0.002, p < 0.0001) among APOE ɛ4 carriers, but not APOE ɛ3 homozygotes (memory: +1 SD increase of BPV: β= 0.0001, p = 0.57; language: β= 0.0001, p = 0.72). Systolic BPV was not significantly associated with change in executive function or visuospatial abilities in APOE ɛ4 carriers (ps = 0.08–0.16) or APOE ɛ3 homozygotes (ps = 0.48–0.12). Conclusion: Cognitive decline associated with high BPV may be specifically accelerated among APOE ɛ4 carriers. [ABSTRACT FROM AUTHOR]

Issue Addressed: Dental caries is highly prevalent in very young Australian and New Zealand children. Health professionals other than registered dental professionals can help prevent early childhood caries, promoting oral health to assist families establish preventative oral health habits at a child's early age. This review identifies oral health promotion (OHP) delivered by nondental health professionals in Australia and New Zealand involving very young children. Methods: Databases (MEDLINE, CINAHL, Embase, Emcare, Web of Science, Scopus, ProQuest, Google Scholar, TROVE) and digital libraries were searched between 2001 and 2021 for eligible studies and grey literature. Studies with a focus on preventative oral health strategies in a primary health care context were included. Results: The review identified 76 studies. Seven met the inclusion criteria, and were conducted in Australia across metropolitan, rural, and remote settings. Studies that successfully engaged nondental health professionals to promote oral health to families reported a positive change in oral health practices among very young children. Delivering OHP during a child's early life stage positively influenced their oral health outcomes. Conclusions: Integration of dental and primary health care increased access to oral health care and advanced positive oral health outcomes for children. With adequate training, resources, and support mechanisms, nondental health professionals can deliver oral health strategies that facilitate behaviour change in parents to improve children's oral health. So What? Health promotion generates enabling conditions that support and empower families to improve and maintain their oral health. Nondental health professionals can play a crucial role promoting oral health for very young children and improving equitable access to preventative oral health care. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effects of the association between two tropical grasses, Signal grass (Brachiaria decumbens) and Napier grass (Pennisetum purpureum) on the proximate composition, in vitro digestibility, and fermentation characteristics of ensiled material. A complete randomized design was used on three treatments namely Signal grass, Napier grass, and Signal-Napier grass combination. Silage was made using molasses applied in proportions of 1:2 with water and mixed with silage at the rate of 5% for a 5kg bag of 2.5cm cut grass. Signal-Napier grass combination silage was superior in almost all parameters to the two sole crop silages. After ensiling, a significant difference (p<0.05) in most parameters was recorded. A significant difference (p=0.0004) in pH was determined where pH was lower in the sole Napier grass silage than that of the Signal-Napier combination and Signal grass. A similar outcome (P<0.05) was recorded for crude protein, ash, ether extracts, nitrogen-free extracts, and neutral detergent fiber. However, no significant difference (p>0.05) was obtained in dry matter (p=0.1524), crude fiber (p=0.5924), and ADF (p=0.1168). Although having poor digestibility values in all treatments, Signal grass proved to be better than the rest. Organoleptic characteristics were promising, with normal color, smell, and texture changes observed. These results indicated that the association of grasses had an impressive positive effect on the nutritional value and quality of silages. Therefore, the use of mixed grass silages is encouraged. [ABSTRACT FROM AUTHOR]

Intravascular schistosomes may control immune and hemostatic responses by regulating the nature and amount of selected host purinergic signaling molecules – such as adenosine triphosphate (ATP), adenosine diphosphate (ADP), and nicotinamide adenine dinucleotide (NAD) – surrounding them. Such metabolites are collectively known as the worm's 'purinergic halo'. Host-interactive, membrane-bound, tegumental ectonucleotidases, notably SmATPDase1, SmNPP5, SmAP and SmNACE, can degrade proinflammatory, prothrombotic and immunomodulatory purinergic metabolites like those listed. A common catabolic product is the anti-inflammatory metabolite adenosine that can additionally be taken in by the worms as food. We envision the tegumental ectonucleotidases as having a twofold role at the worm surface: first, they degrade potentially harmful host signaling molecules, and second, they generate vital nutrients around the worms from where these can be conveniently imported. Blood stage Schistosoma mansoni expresses a series of membrane-bound, tegumental ectonucleotidases at the host–parasite interface that are designated SmATPDase1, SmNPP5, SmAP, and SmNACE. These enzymes can degrade exogenous, host purinergic signaling molecules such as proinflammatory adenosine triphosphate (ATP), prothrombotic adenosine diphosphate (ADP), and immunomodulatory nicotinamide adenine dinucleotide (NAD), to control what is collectively known as the worm's 'purinergic halo'. A common product of purinergic catabolism is the anti-inflammatory metabolite adenosine. Since schistosomes cannot synthesize purines de novo , adenosine can additionally be taken in by the worms as food. In this manner, schistosome tegumental ectonucleotidases not only degrade potentially harmful host signaling molecules but additionally generate vital nutrients in the vicinity of the worms from where these can be conveniently taken in. [ABSTRACT FROM AUTHOR]

This study explored the use of collaborative action research (CAR) in a year-long professional development (PD) for global climate change (GCC) education. The purpose was to understand how high school science teachers' engagement in CAR affected their classroom practice. The teachers exchanged stories of practice, shared and tried out new ideas in their classrooms, and engaged in systematic inquiry. The study was guided by these questions: What are the effects of extended professional development on the teachers' classroom practice? What role did action research play in reaching our goals for professional development? What affordances and obstacles affect their change in pedagogy? Data included recordings of CAR meetings, classroom observations, and post-interviews with teachers. Data were analyzed through coding processes and the development of learning progressions to understand how the teachers' knowledge developed throughout the PD. Results indicated teachers changes their practice and demonstrated increased confidence in teaching GCC science. They incorporated discussion and argumentation into their teaching practice, utilized a more place-based approach to GCC education, and presented GCC as real and anthropogenic. It was also found that the complexities of teachers' lives inhibited the full participation of all the teachers who volunteered to engage in CAR. [ABSTRACT FROM AUTHOR]

Engineers may be technically competent; however, some lack the communication skills necessary to transfer information and reason. This situation makes excellent technical skills superfluous. In this paper, communication is reviewed from a reliability engineering viewpoint, discussing why conveying well-crafted information to decision-makers is pivotal to success. Firstly, the authors examine several engineering communication myths. The authors then present how good communication fundamentals can be used to meet the decision-maker requirements leading to the desired engineering outcomes. Next, the authors narrow the scope to examine presenting reliability growth plans and their associated risk to decision-makers from a reliability engineering perspective. The paper concludes with an analysis of the robustness of reliability estimates and why distribution or interval estimators should always be preferable to point estimators when describing reliability metrics. While the paper focuses on reliability engineering practitioners and their efforts, the content is helpful for other engineering specialists when considering communication. [ABSTRACT FROM AUTHOR]

The onset of literacy marks a significant change in children's development. Written language is more complex than everyday conversation, and even books targeted at preschoolers contain more varied words and more complex syntax than child-directed speech does. We review the nature and content of children's book language, focusing on recent large-scale corpus analyses that systematically compared written and spoken language. We argue that exposure to book language provides opportunities for learning words and syntactic constructions that are only rarely encountered in speech and that, in turn, this rich experience drives further developments in language and literacy. Moreover, we speculate that the range, variety, depth, and sophistication of book language provide key input that promotes children's social and emotional development. Becoming literate changes things, and researchers need to better understand how and why reading experience shapes people's minds and becomes associated with a range of skills and abilities across the life span. [ABSTRACT FROM AUTHOR]

This study explored whether a daytime nap aids children's acquisition of letter‐sound knowledge, which is a fundamental component for learning to read. Thirty‐two preschool children in Sydney, Australia (Mage = 4 years;3 months) were taught letter‐sound mappings in two sessions: one followed by a nap and the other by a wakeful period. Learning was assessed by explicit letter‐sound mappings ("Which sound does this letter make?") and knowledge generalization tasks ("Here's Tav and Cav, which one is /kav/?"). Results from the knowledge generalization task showed better performance after a nap than after wake. However, no nap benefit was found for explicit letter‐sound knowledge. This study provides initial evidence that naps could be beneficial for preschool children's learning of letter‐sound mappings. [ABSTRACT FROM AUTHOR]

Abstract Objective Methods Results Conclusions Young Black men who have sex with men (MSM) represent the majority of individuals with new HIV infections in the U.S. Substance use is related to risk and acquisition t of HIV. The purpose of this study was to explore the perceptions and experiences about the role substance use plays in the lives HIV-positive and HIV-negative young Black MSM between the ages of 18-34.Using a qualitative, narrative perspective, we recruited and then interviewed participants in partnership with AIDS Service Organizations. Narrative and thematic analysis was used to analyze these Black men’s personal stories with harm reduction used as the conceptual approach.Nine HIV-positive and 3 HIV-negative participants(n = 12) shared stories about their own personal experiences with family relationships and substance use. Themes related to family included early exposure and initiation of substance use, substance use as a response to stigma around sexual orientation, kicked out of house, asked to leave or left home so they could be themselves and perceived benefits and advantages of methamphetamine.The participants are subjected to adverse and stressful childhood experiences. These are important stories to understand if we expect to mount an adequate response, utilizing harm reduction, to the growing number of young Black MSM at-risk for HIV. [ABSTRACT FROM AUTHOR]

A variety is primitive if every subquasivariety is equational, i.e. a subvariety. In this paper, we explore the connection between primitive lattice varieties and Whitman's condition (W). For example, if every finite subdirectly irreducible lattice in a locally finite variety satisfies Whitman's condition (W), then is primitive. This allows us to construct infinitely many sequences of primitive lattice varieties, and to show that there are 2 ℵ 0 such varieties. Some lattices that fail (W) also generate primitive varieties. But if I is a (W)-failure interval in a finite subdirectly irreducible lattice L , and L [ I ] denotes the lattice with I doubled, then (L [ I ]) is never primitive. [ABSTRACT FROM AUTHOR]

Infection with schistosomes (blood flukes) can result in the debilitating disease schistosomiasis. These parasites survive in their host for many years, and we hypothesize that proteins on their tegumental surface, interacting with the host microenvironment, facilitate longevity. One such ectoenzyme -- the nucleotide pyrophosphatase/phosphodiesterase SmNPP5 can cleave ADP (to prevent platelet aggregation) and NAD (likely preventing Treg apoptosis). A second tegumental ectoenzyme, the glycohydrolase SmNACE, also catabolizes NAD. Here, we undertake a comparative biochemical characterization of these parasite ectoenzymes. Both are GPI-linked and exhibit different optimal pH ranges. While SmNPP5 requires divalent cations, SmNACE does not. The KM values of the two enzymes for NAD at physiological pH differ: SmNPP5, KM = 340 mM± 44; SmNACE, KM = 49 mM± 4. NAD cleavage by each enzyme yields different products. SmNPP5 cleaves NAD to form nicotinamide mononucleotide (NMN) and AMP, whereas SmNACE cleaves NAD to generate nicotinamide (NAM) and adenosine diphosphate ribose (ADPR). Each enzyme can process the other's reaction product. Thus, SmNACE cleaves NMN (to yield NAM and ribose phosphate) and SmNPP5 cleaves ADPR (yielding AMP and ribose phosphate). Metabolomic analysis of plasma containing adult worms supports the idea that these cleavage pathways are active in vivo. We hypothesize that a primary function of SmNPP5 is to cleave NAD to control host immune cell function and a primary function of SmNACE is to cleave NMN to generate the vital nutrient nicotinamide (vitamin B3) for convenient uptake by the worms. Chemical inhibition of one or both ectoenzymes could upset worm metabolism and control schistosome infection. [ABSTRACT FROM AUTHOR]

Determining an effective dosing regimen for piperacillin–tazobactam in critically ill patients is challenging due to substantial pharmacokinetic variability caused by complex pathophysiological changes. To address this need, a prospective clinical study was conducted, which enrolled 112 critically ill patients and employed an opportunistic sampling strategy. Population modeling and simulation were performed to characterize the pharmacokinetics (PK) and probability of target attainment (PTA) of piperacillin–tazobactam under various dosing regimens. Both piperacillin and tazobactam final models were one‐compartment models with zero‐order input and first‐order elimination. Significant covariates included lean body weight for piperacillin and creatinine clearance along with continuous renal replacement therapy (CRRT) for both drugs. Monte Carlo simulations demonstrated that continuous infusion can achieve higher PTA than intermittent and extended infusions. When considering the minimum inhibitory concentration (MIC) of 16 mg/L for Pseudomonas aeruginosa (a frequently encountered bacterial pathogen among critically ill patients) and a PK/PD target of 100% fT >MIC, continuous infusion of 6 g/day is recommended for critically ill patients with a CLcr <60 mL/min, 9 g/day for patients with CLcr in the range of 60 to 129 mL/min, and 12 g/day for patients with a CLcr ≥130 mL/min. In addition, extended infusion represents a good alternative, especially the 3 g q6h or 4 g q6h regimens which can achieve the designated European Committee on Antimicrobial Susceptibility Testing (EUCAST) non‐species‐related PK/PD breakpoint of 8 mg/L. Our study provided valuable insight into PTA outcomes, which, together with individual renal function of future patients and institution‐specific piperacillin susceptibility patterns, may assist physicians when making dosing decisions. [ABSTRACT FROM AUTHOR]

Words that can be easily placed in contexts are more easily processed, yet norms for context availability are limited. Here, participants rated 3,000 words for context availability and sentence availability, a new metric predicted to capture information relating to textual variation. Both variables were investigated alongside other word-level characteristics to explore lexical-semantic space. Analyses demonstrated that context availability and sentence availability are distinct. Context availability covaries with concreteness and imageability, while sentence availability captures information relating to contextual variation, frequency and ambiguity. Analyses of megastudy data showed that both context availability and sentence availability uniquely facilitated lexical decision performance. [ABSTRACT FROM AUTHOR]

Polymyxin B (PMB) has reemerged as a last‐line therapy for infections caused by multidrug‐resistant gram‐negative pathogens, but dosing is challenging because of its narrow therapeutic window and pharmacokinetic (PK) variability. Population PK (POPPK) models based on suitably powered clinical studies with appropriate sampling strategies that take variability into consideration can inform PMB dosing to maximize efficacy and minimize toxicity and resistance. Here we reviewed published PMB POPPK models and evaluated them using an external validation data set (EVD) of patients who are critically ill and enrolled in an ongoing clinical study to assess their utility. Seven published POPPK models were employed using the reported model equations, parameter values, covariate relationships, interpatient variability, parameter covariance, and unexplained residual variability in NONMEM (Version 7.4.3). The predictive ability of the models was assessed using prediction‐based and simulation‐based diagnostics. Patient characteristics and treatment information were comparable across studies and with the EVD (n = 40), but the sampling strategy was a main source of PK variability across studies. All models visually and statistically underpredicted EVD plasma concentrations, but the two‐compartment models more accurately described the external data set. As current POPPK models were inadequately predictive of the EVD, creation of a new POPPK model based on an appropriately powered clinical study with an informed PK sampling strategy would be expected to improve characterization of PMB PK and identify covariates to explain interpatient variability. Such a model would support model‐informed precision dosing frameworks, which are urgently needed to improve PMB treatment efficacy, limit resistance, and reduce toxicity in patients who are critically ill. [ABSTRACT FROM AUTHOR]

One of the hallmarks of the immune system is a dynamic landscape of cellular communication through the secretion of soluble factors, production of cell‐bound ligands, and expression of surface receptors. This communication affects all aspects of immune cell behavior, integrates the responses of immune cells in tissues, and is fundamental to orchestrating effective immunity. Recent pioneering work has shown that the transfer of ribonucleic acids (RNAs) constitutes a novel mode of cellular communication. This communication involves diverse RNA species, with short noncoding RNAs especially enriched in the extracellular space. These RNAs are highly stable and selectively packaged for secretion. Transferred RNAs have functions in target cells that both mirror their cell‐intrinsic roles and adopt novel mechanisms of action. These extracellular RNAs both impact the behavior of individual immune cells and participate in local and systemic immune responses. The impacts of RNA communication on immune cells and disease states have important implications for the development of novel clinical biomarkers and innovative therapeutic designs in immune‐related disease. In this review, we will discuss the foundation of knowledge that is establishing RNA communication as an active and functional process in the immune system. [ABSTRACT FROM AUTHOR]

This study applied two mathematical algorithms, lattice up-stream targeting (LUST) andD-basis, to the identification of prognostic signatures from cancer gene expression data. The LUST algorithm looks for metagenes, which are sets of genes that are either overexpressed or underexpressed in the same patients. Whereas LUST runs unsupervised by clinical data, theD-basis algorithm uses implications and association rules to relate gene expression to clinical outcomes. TheD-basis selects a small subset of the metagene (a signature) to predict survival. The two algorithms, LUST and D-basis, were combined and applied to mRNA expression and clinical data from The Cancer Genome Atlas (TCGA) for 203 stage 1 and 2 stomach cancer patients. Two small (four-gene) signatures effectively predict survival in early-stage stomach cancer patients. These signatures could be used as a guide for treatment. The first signature (DU4) consists of genes that are underexpressed on the long-survival/low-risk group: FLRT2, KCNB1, MYOC, and TNXB. The second signature consists of genes that are overexpressed on the short-survival/high-risk group: ASB5, SFRP1, SMYD1, and TACR2. Another nine-gene signature (REC9) predicts recurrence: BNC2, CCDC8, DPYSL3, MOXD1, MXRA8, PRELP, SCARF2, TAGLN, and ZNF423. Each patient is assigned a score that is a linear combination of the expression levels for the genes in the signature. Scores below a selected threshold predict low-risk/long survival, whereas high scores indicate a high risk of short survival. The metagenes associate with TCGA cluster C1. Both our signatures and cluster C1 identify tumors that are genomically silent, and have a low mutation load or mutation count. Furthermore, our signatures identify tumors that are predominantly in the WHO classification of poorly cohesive and the Lauren class of diffuse samples, which have a poor prognosis. [ABSTRACT FROM AUTHOR]

Given our rapidly changing world and the pressing challenges of climate change and health care, it is more important than ever for youth and the broader public to learn scientific knowledge and skills. To reach the most people possible and increase diversity in Science, Technology, Engineering, and Mathematics (STEM) fields, we need compelling educational approaches that incorporate the lived experiences of students. Partnerships between researchers, scientists, educators, and community groups can enrich and extend scientists' research while providing authentic scientific learning experiences for undergraduate and K-12 students, especially from STEM-underrepresented groups. However, more research is needed on equitable long-term partnerships, including how these projects are organized and how partners align their interests and goals. In this article, we present recommendations from research–practice partnership projects that utilize a Community STEM model, an approach that draws from individual and collective strengths, contextualizes science learning, and positions youth as producers of content and artifacts. To situate this work, we review and highlight biology-related citizen and community science projects designed for youth. We characterize projects according to their goals and format, provide illustrative examples of three programs, and provide recommendations for other scientists and researchers. Overall, this article reviews research on all three approaches for partnerships (citizen science, community science, and community STEM) to provide recommendations for scientists who are interested in establishing partnerships within their communities. Limitations of each approach are described as well as areas for further research. [ABSTRACT FROM AUTHOR]

The Notch signaling pathway is an evolutionarily conserved cell signaling system known to be involved in vascular development and function. Recent evidence suggests that dysfunctional Notch signaling could play a critical role in the pathophysiology of neurodegenerative diseases. We reviewed current literature on the role of Notch signaling pathway, and specifically Notch receptor genes and proteins, in aging, cerebrovascular disease and Alzheimer's disease. We hypothesize that Notch signaling may represent a key point of overlap between age-related vascular and Alzheimer's pathophysiology contributing to their comorbidity and combined influence on cognitive decline and dementia. Numerous findings from studies of genetics, neuropathology and cell culture models all suggest a link between altered Notch signaling and Alzheimer's pathophysiology. Age-related changes in Notch signaling may also trigger neurovascular dysfunction, contributing to the development of neurodegenerative diseases; however, additional studies are warranted. Future research directly exploring the influence of aberrant Notch signaling in the development of Alzheimer's disease is needed to better understand this mechanism. [ABSTRACT FROM AUTHOR]

Employee Assistance Programs (EAPs) have been responding for decades to challenges put forth by employers and employees. The COVID-19 pandemic has brought forth new considerations for EAPs and has also highlighted preexisting challenges to the EAP value proposition. This paper highlights those challenges using examples from a specific internal EAP (Mayo Clinic Rochester) and observations about overall EAP acute trends as well. The future of EAP and evolution of EAP services are discussed in light of the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

First, the small number of articles in this issue suggest that examining structural marginalization is still an emerging area of research on violence and violence prevention. Scholarly research has used many terms to describe aspects of structural marginalization, using terms like structural inequity, institutional racism, and structural violence to highlight specific elements of marginalization. Recent calls for social and racial justice highlight the persistent questions about the relation between structural marginalization and violence (Frimpong, 2020). [Extracted from the article]

The authors discuss the social and structural determinants of youth violence in the U.S. They mention the impact of violence on Black youth, the social and structural problems that Black youth face that contribute to violence, and the opportunities for youth to contribute to the prevention of violence in their communities.

• 1st study to directly compare effect of 2+1 schedule of PCV10 or PCV13 on carriage. • Includes an unvaccinated comparator group. • Both PCVs reduce carriage of serotypes in the corresponding vaccine. • May be some differences between the vaccines in their impact on carriage. • Majority of carriage was vaccine-type, so both vaccines likely to be beneficial. Pneumococcal conjugate vaccines (PCVs) generate herd protection by reducing nasopharyngeal (NP) carriage. Two PCVs, PCV10 and PCV13, have been in use for over a decade, yet there are few data comparing their impact on carriage. Here we report their effect on carriage in a 2+1 schedule, compared with each other and with unvaccinated controls. Data from four groups within a parallel, open-label randomised controlled trial in Ho Chi Minh City contribute to this article. Three groups were randomised to receive a 2+1 schedule of PCV10 (n = 250), a 2+1 schedule of PCV13 (n = 251), or two doses of PCV10 at 18 and 24 months (controls, n = 197). An additional group (n = 199) was recruited at 18 months to serve as controls from 18 to 24 months. NP swabs collected at 2, 6, 9, 12, 18, and 24 months were analysed (blinded) for pneumococcal carriage. This study aimed to determine if PCV10 and PCV13 have a differential effect on pneumococcal carriage, a secondary outcome of the trial. We also describe the serotype distribution among unvaccinated participants. Trial registration: ClinicalTrials.gov NCT01953510. Compared with unvaccinated controls, a 2+1 schedule of PCV10 reduced PCV10-type carriage by 45–62% from pre-booster through to 24 months of age, and a 2+1 schedule of PCV13 reduced PCV13-type carriage by 36–49% at 12 and 18 months of age. Compared directly with each other, there were few differences between the vaccines in their impact on carriage. Vaccine serotypes accounted for the majority of carriage in unvaccinated participants. Both PCV10 and PCV13 reduce the carriage of pneumococcal vaccine serotypes. The introduction of either vaccine would have the potential to generate significant herd protection in this population. National Health and Medical Research Council of Australia, Bill & Melinda Gates Foundation. [ABSTRACT FROM AUTHOR]

This experiment investigated comprehension monitoring in children learning English as an additional language (EAL) compared to monolinguals. Sixty-three 9–10-year-old children read texts containing an internal inconsistency (e.g. a barking kitten vs. barking puppy) while their eye movements were monitored. Standardized tests measured word reading fluency and vocabulary size and the children completed a questionnaire tapping rereading behavior. There was no overall difference between EAL and monolingual children. Regardless of EAL status, children with larger vocabularies were more efficient in their re-analysis of inconsistent information, as revealed by regressive eye movements. As efficient re-analysis of inconsistent information is essential for comprehension and is ubiquitous in proficient readers, the presence of this pattern in the children is indicative of successful online monitoring. However, rereading of inconsistent vs consistent words in the eye movement record was not related to children's self-reported rereading, not providing any support for deliberate rereading. Our findings indicate that successful online monitoring relies on strong word knowledge leading to efficient processing of texts, both for bilingual and monolingual children, and beyond deliberate rereading. [ABSTRACT FROM AUTHOR]

Under broad finiteness conditions, such as the existence of a greatest or least element, a semidistributive lattice has the two element lattice as a homomorphic image, and so, if it has more than two elements, is not simple. However, the existence of a simple, semidistributive lattice with more than two elements has remained in question. This paper constructs such a lattice. [ABSTRACT FROM AUTHOR]

• Remote dried blood spot (DBS) self-collection in older adults is highly feasible. • Remote DBS yields high-quality spots, sufficient for assaying multiple biomarkers, with high participant adherence. • Inflammatory markers (CRP, IL-6, TNF-α) from self-collected DBS are reliable and valid. Dried blood spots (DBS) provide a minimally invasive method to assess inflammatory markers and can be collected remotely at-home or in-person in the lab. However, there is a lack of methodological information comparing these different collection methods and in older adults. We investigated the feasibility (including adherence, yield, quality, and participant preferences) and measurement properties (reliability, validity) of remotely collected DBS inflammatory markers in older adults. Participants (N = 167, mean age = 72, range: 60–96 years) collected their own DBS (finger prick on filter paper) during three remote interviews over ∼ 6 months. Within 4–5 days on average of their last remote interview, a subset of 41 participants also attended an in-person lab visit that included a researcher-collected DBS sample, venous blood draw, and survey to assess participant preferences of DBS collection. DBS and venous blood were assayed for CRP, IL-6, and TNF-α. Adherence: 98% of expected DBS samples (493 out of 501) were completed and mailed back to the lab. Yield: 97% of DBS samples were sufficient for all assays. Quality: On average, 0.80 fewer optimal spots (60uL of blood that filled the entire circle) were obtained remotely vs. in-person (p = 0.013), but the number of useable or better spots (at least 30-40uL of blood) did not differ (p = 0.89). Preference: A slight majority of participants (54%) preferred in-person DBS collection. Reliability: DBS test–retest reliabilities were good: CRP (ICC = 0.74), IL-6 (ICC = 0.76), and TNF-α (ICC = 0.70). Validity: Inflammatory levels from DBS correlated strongly with levels from venous blood (r = 0.60-0.99) and correlated as expected with sociodemographic and physical health and function variables. Older adults can remotely collect their own DBS to acquire reliable and valid inflammatory data. Remote DBS collection is highly feasible and may allow for inflammatory markers to be assessed in larger, more representative samples than are possible with lab- or clinic-based research designs. [ABSTRACT FROM AUTHOR]

We describe a case of limb-threatening osteomyelitis and metalware infection with carbapenemase-producing extensively drug-resistant Pseudomonas aeruginosa successfully cured with aggressive surgical debridement and combined intravenous fosfomycin and colistin. Real-time therapeutic drug monitoring was used to maximize probability of efficacy and minimize potential for toxicity. [ABSTRACT FROM AUTHOR]

Background Data on influenza vaccine effectiveness (IVE) against mortality are limited, with no Australian data to guide vaccine uptake. We aimed to assess IVE against influenza-related mortality in Australian hospitalized patients, assess residual confounding in the association between influenza vaccination and mortality, and assess whether influenza vaccination reduces the severity of influenza illness. Methods Data were collected between 2010 and 2017 from a national Australian hospital-based sentinel surveillance system using a case-control design. Adults and children admitted to the 17 study hospitals with acute respiratory symptoms were tested for influenza using nucleic acid testing; all eligible test-positive cases, and a subset of test-negative controls, were included. Propensity score analysis and multivariable logistic regression were used to determine the adjusted odds ratio (aOR) of vaccination, with IVE = 1 – aOR × 100%. Residual confounding was assessed by examining mortality in controls. Results Over 8 seasons, 14038 patients were admitted with laboratory-confirmed influenza. The primary analysis included 9298 cases and 6451 controls, with 194 cases and 136 controls dying during hospitalization. Vaccination was associated with a 31% (95% confidence interval [CI], 3%–51%; P =.033) reduction in influenza-related mortality, with similar estimates in the National Immunisation Program target group. Residual confounding was identified in patients ≥65 years old (aOR, 1.92 [95% CI, 1.06–3.46]; P =.031). There was no evidence that vaccination reduced the severity of influenza illness (aOR, 1.07 [95% CI,.76–1.50]; P =.713). Conclusions Influenza vaccination is associated with a moderate reduction in influenza-related mortality. This finding reinforces the utility of the Australian vaccination program in protecting those most at risk of influenza-related deaths. [ABSTRACT FROM AUTHOR]

Introduction: Nasal chondromesenchymal tumors (NCMT) are rare benign neoplasms that usually present in children <1 year of age. They can display rapid growth and significant local bony remodeling that can mimic a malignant process. Of the ∼50 published cases to date, few have documented the need for neurosurgical intervention. We herein report a NCMT in an infant treated with a staged cranial and transnasal approach, as well as summarize the available literature on this pathology. Case Report: A newborn male with a compromised airway was noted to have a large sinonasal lesion. After stabilization, MRI demonstrated a 4-cm enhancing mass with diffuse sinus involvement and significant extension into the anterior cranial fossa, with displacement of the optic apparatus and hypothalamic pituitary axis. After an initial biopsy, the patient underwent a bifrontal craniofacial approach at 2 months of age, followed by a second-stage transnasal endoscopic approach at 15 months which resulted in a complete resection. There were no neurosurgical complications. Pathology was consistent with a NCMT. Discussion: Although rare, neurosurgical involvement is critical for the treatment of NCMTs with intracranial extension. Staged cranial and endonasal endoscopic approaches may be needed for complete resection of such lesions. [ABSTRACT FROM AUTHOR]

The academy's ignorance about and resultant bias against Indigenous Americans, their histories, cultures, legal status, and present circumstances have consequences impacting people ranging from American Supreme Court Justices to soccer players. Too often these consequences create disastrous results for First Nations people as well as for the greater society. To address this nescience, university personnel should include Indigenous American studies in their curricula; English professors should teach works by First Nations and American Indian people; and humanities departments should offer Native art and music courses on a permanent basis. Universities should actively recruit, hire, and properly mentor Native students and faculty members. Faculty should engage themselves with student follow-ups and job placements. Professors, editors, and critics should read Native papers and publications from Indigenous perspectives, not Western ones. Students and tribes can also do their part to end academic racism: Indigenous scholars by organizing themselves into associations promoting information exchange and support, and tribal leaders by conscientiously buttressing their members' progress through financial and political assistance. [ABSTRACT FROM AUTHOR]

Background: Gender differences have been noted in studies linking blood pressure to all-cause dementia, and the two most common forms of dementia: Alzheimer's disease (AD) and vascular dementia (VaD). However, how gender modifies the relationship between blood pressure and dementia remains unclear.Objective: To review evidence for a gender modifying effect on the link between blood pressure and all-cause dementia.Methods: A systematic review was conducted according to PRISMA guidelines. Sixteen out of 256 reviewed articles met inclusion criteria.Results: For women, higher midlife systolic blood pressure (SBP) and hypertension were both associated with greater risk of all-cause dementia, AD, and VaD, in six out of seven studies. Two of these studies reported higher midlife SBP/hypertension were associated with greater risk for all-cause dementia in women, but not men. One study reported higher midlife SBP associated with greater AD risk in women, but not men. However, another study reported that midlife hypertension associated with AD risk in men, but not women. No clear gender differences were reported in the relationship between late-life high blood pressure/hypertension with all-cause dementia or AD.Conclusion: Studies rarely, and inconsistently, analyzed or reported gender effects. Therefore, interpretation of available evidence regarding the role of gender in blood pressure associated dementia was difficult. Several studies indicated higher midlife SBP was associated with greater risk of all-cause dementia for women, compared to men. Future studies should evaluate women-specific aging processes that occur in midlife when considering the association between blood pressure and dementia risk. [ABSTRACT FROM AUTHOR]

Background: Elevated blood pressure is linked to cognitive impairment and Alzheimer's disease (AD) biomarker abnormality. However, blood pressure levels vary over time. Less is known about the role of long-term blood pressure variability in cognitive impairment and AD pathophysiology.Objective: Determine whether long-term blood pressure variability is elevated across the clinical and biomarker spectrum of AD.Methods: Alzheimer's Disease Neuroimaging Initiative participants (cognitively normal, mild cognitive impairment, AD [n = 1,421]) underwent baseline exam, including blood pressure measurement at 0, 6, and 12 months. A subset (n = 318) underwent baseline lumbar puncture to determine cerebrospinal fluid amyloid-β and phosphorylated tau levels. Clinical groups and biomarker-confirmed AD groups were compared on blood pressure variability over 12 months.Results: Systolic blood pressure variability was elevated in clinically diagnosed AD dementia (VIM: F2,1195 = 6.657, p = 0.001, η2 = 0.01) compared to cognitively normal participants (p = 0.001), and in mild cognitive impairment relative to cognitively normal participants (p = 0.01). Findings were maintained in biomarker-confirmed AD (VIM: F2,850 = 5.216, p = 0.006, η2 = 0.01), such that systolic blood pressure variability was elevated in biomarker-confirmed dementia due to AD relative to cognitively normal participants (p = 0.005) and in biomarker-confirmed mild cognitive impairment due to AD compared to cognitively normal participants (p = 0.04).Conclusion: Long-term systolic blood pressure variability is elevated in cognitive impairment due to AD. Blood pressure variability may represent an understudied aspect of vascular dysfunction in AD with potential clinical implications. [ABSTRACT FROM AUTHOR]

The Australian Federal Government legalised access to medicinal cannabis in 2016. More than 100 different cannabis products are now available to prescribe. Most are oral preparations (oils) or capsules containing delta-9-tetrahydrocannabinol or cannabidiol. Driedflower products are also available. As most products are unregistered drugs, prescribing requires approval under the Therapeutic Goods Administration Special Access Scheme-B or Authorised Prescriber Scheme. Special Access Scheme Category B applications can be made online, with approval usually being given within 24-48 hours. However, supply chain problems may delay dispensing by the pharmacy. By the end of 2019, over 28,000 prescribing approvals had been issued to patients, involving more than 1400 doctors, mostly GPs. More than 70,000 approvals are projected by the end of 2020. Most prescriptions are for chronic non-cancer pain, anxiety, cancer-related symptoms, epilepsy and other neurological disorders. However, the evidence supporting some indications is limited. Many doctors are cautious about prescribing cannabis. While serious adverse events are rare, there are legitimate concerns around driving, cognitive impairment and drug dependence with products containing delta-9-tetrahydrocannabinol. Cannabidiol-only products pose fewer risks. [ABSTRACT FROM AUTHOR]

Purpose Drug-induced liver injury (DILI) that progresses to acute liver failure (ALF) has a high mortality rate, and therapeutic options are limited. Acetylcysteine has a labeled indication for use as an antidote for acetaminophen toxicity and has also been used with limited success in treatment of non–acetaminophen-induced liver injury, with small clinical trials indicating an increase in transplant-free survival. Recommendations for management of non–acetaminophen-induced DILI include withdrawal of the offending agent and supportive care. Treatment guidelines generally discourage a rechallenge with an offending medication, except in cases where there are no other therapeutic options for management of a serious disease, such as active tuberculosis (TB). Summary This case report describes the reversal of ALF due to DILI in a patient receiving antitubercular agents for active TB. After withdrawal of initially prescribed antitubercular agents, the patient was switched to a less hepatotoxic anti-TB regimen and intravenous acetylcysteine pending results of antimicrobial susceptibility testing. After stabilization of the patient's liver enzyme levels, intravenous acetylcysteine was discontinued and oral acetylcysteine was continued for 5 days without an increase in hepatic enzyme levels or clinical deterioration. After 5 days, oral acetylcysteine was discontinued due to patient-reported nausea and vomiting. Conclusion Given the limited number of therapeutic interventions shown to be beneficial in ALF and data suggesting a protective effect against DILI with initiation of acetylcysteine at the start of treatment with anti-TB medications, acetylcysteine can be considered for patients with anti-TB – associated DILI. [ABSTRACT FROM AUTHOR]

An introduction to the journal is presented in which the editor discusses the various articles published within the issue on topics like dyslexia, the London World Blind Centre, and dyslexia's relationship with class and gender.

We present evidence of inverse Hall-Petch behavior for a single-phase high entropy alloy (CoCrFeMnNi) in ultra-high vacuum and show that it is associated with low friction coefficients (~0.3). Grain size measurements by STEM validate a recently proposed dynamic amorphization model that accurately predicts grain size-dependent shear strength in the inverse Hall-Petch regime. Wear rates in the initially soft (coarse grained) material were shown to be remarkably low (~10–6 mm3/N-m), the lowest for any HEA tested in an inert environment where oxidation and the formation of mixed metal-oxide films is mitigated. The combined high wear resistance and low friction are linked to the formation of an ultra-nanocrystalline near-surface layer. The dynamic amorphization model was also used to predict an average high angle grain boundary energy (0.87 J/m2). This value was used to explain cavitation-induced nanoporosity found in the highly deformed surface layer, a phenomenon that has been linked to superplasticity. [ABSTRACT FROM AUTHOR]