Nemabiome metabarcoding shows a high prevalence of Haemonchus contortus and predominance of Camelostrongylus mentulatus in alpaca herds in the northern UK.

Gastrointestinal nematodes (GINs) are a common threat faced by pastoral livestock. Since their major introduction to the UK in the early 1990s, South American camelids have been cograzed with sheep, horses, and other livestock, allowing exposure to a range of GIN species. However, there have been no molecular-based studies to investigate the GIN populations present in these camelids. In the current study, we sampled nine alpaca herds from northern England and southern Scotland and used high-throughput metabarcoded sequencing to describe their GIN species composition. A total of 71 amplicon sequence variants (ASVs) were identified representing eight known GIN species. Haemonchus contortus was the most prevalent species found in almost all herds in significant proportions. The identification of H. contortus in other livestock species is unusual in the northern UK, implying that alpacas may be suitable hosts and potential reservoirs for infection in other hosts. In addition, the camelid-adapted GIN species Camelostrongylus mentulatus was identified predominantly in herds with higher faecal egg counts. These findings highlight the value of applying advanced molecular methods, such as nemabiome metabarcoding to describe the dynamics of gastrointestinal nematode infections in novel situations. The results provide a strong base for further studies involving cograzing animals to confirm the potential role of alpacas in transmitting GIN species between hosts.

COMPARISON OF SUBCUTANEOUS ALFAXALONE AND SUBCUTANEOUS ALFAXALONE-DEXMEDETOMIDINE FOR SEDATION IN THE HOUSTON TOAD (ANAXYRUS HOUSTONENSIS).

The Houston toad (Anaxyrus houstonensis), a primarily terrestrial amphibian of south-central Texas, has been listed as federally endangered since 1970. Sedation is an important tool for obtaining diagnostics and providing treatment in this species. This prospective, randomized, and blinded study compared the sedative effects of SC alfaxalone (Protocol A) at approximately 12 mg/kg (median [range] = 12.70 [12.09-13.95] mg/kg] to SC alfaxalone-dexmedetomidine (Protocol AD) at approximately 12 mg/kg (median [range] = 12.68 [12.16-13.56] mg/kg) and 0.1 mg/kg (median [range] = 0.1 [0.07-0.13] mg/kg), respectively, in adult Houston toads (n = 26). Toads from Protocol AD received atipamezole SC at approximately 1 mg/kg (median [range] = 0.96 [0.75-1.25] mg/kg) 45 min postinduction, whereas toads from Protocol A received the equivalent volume of SC sterile saline at the same time point. Heart rate, gular rate, and times to first effect, loss of righting reflex, ability to position for radiographs, loss of nociception, return of righting reflex, and full recovery were recorded. A significantly greater number of toads lost righting reflex, positioned for radiographs, and lost nociception with Protocol AD compared with Protocol A. Additionally, time to return of righting reflex and time to full recovery were significantly longer with Protocol AD than with Protocol A. The protocols did not differ significantly in time to first effect, time to radiographic positioning, or time to loss of nociception. Histologic examination of four toads euthanized during the study revealed acute injection site reactions from all administered drugs, including saline. No clinical adverse reactions were observed. This study demonstrates that the combination of SC alfaxalone and dexmedetomidine results in deeper sedation than SC alfaxalone alone, but also correlates with longer recovery times despite antagonist administration.

A Three-Step Method for the Preparation of N-Substituted 3,4-Dihydroisoquinolin-1(2H)-ones and Heteroaryl-Fused 3,4-Dihydropyridin-2(1H)-ones from 2-Bromobenzoate Precursors.

We demonstrate a general method for the preparation of diverse N-substituted 3,4-dihydroisoquinolin-1(2H)-one compounds through an overall three-step cross-coupling/cyclization/N-deprotection/N-alkylation sequence. In the first step, ethyl 2-bromobenzoates and 2-bromo-1-carboxyethyl heterocycles are cross-coupled with commercially available potassium (2-((tert-butoxycarbonyl)amino)ethyl)trifluoroborate to produce (hetero)aryl-substituted 3-[(N-Boc-2-carboxyethyl)phenyl]ethylamines. In a subsequent two-stage process, these (hetero)arylethylamines undergo base-mediated ring closure followed by N-deprotection and N-alkylation to produce N-substituted 3,4-dihydroisoquinolin-1(2H)-ones and heteroaryl-fused N-benzyl 3,4-dihydropyridin-2(1H)-ones. Mechanistic work was performed to elucidate the order of transformations for the latter two-stage process. The method was also extended to the production of N-benzyl isoindolin-1-one and N-benzyl 2,3,4,5-tetrahydro-1H-benzo[c]azepin-1-one.

MEK1/2 activity modulates TREM2 cell surface recruitment.

Rare sequence variants in the microglial cell surface receptor TREM2 have been shown to increase the risk for Alzheimer's disease (AD). Disease-linked TREM2 mutations seem to confer a partial loss of function, and increasing TREM2 cell surface expression and thereby its function(s) might have therapeutic benefit in AD. However, druggable targets that could modulate microglial TREM2 surface expression are not known. To identify such targets, we conducted a screen of small molecule compounds with known pharmacology using human myeloid cells, searching for those that enhance TREM2 protein at the cell surface. Inhibitors of the kinases MEK1/2 displayed the strongest and most consistent increases in cell surface TREM2 protein, identifying a previously unreported pathway for TREM2 regulation. Unexpectedly, inhibitors of the downstream effector ERK kinases did not have the same effect, suggesting that noncanonical MEK signaling regulates TREM2 trafficking. In addition, siRNA knockdown experiments confirmed that decreased MEK1 and MEK2 were required for this recruitment. In iPSC-derived microglia, MEK inhibition increased cell surface TREM2 only modestly, so various cytokines were used to alter iPSC microglia phenotype, making cells more sensitive to MEK inhibitor-induced TREM2 recruitment. Of those tested, only IFN-gamma priming prior to MEK inhibitor treatment resulted in greater TREM2 recruitment. These data identify the first known mechanisms for increasing surface TREM2 protein and TREM2-regulated function in human myeloid cells and are the first to show a role for MEK1/MEK2 signaling in TREM2 activity.

Sex-dependent role of Pannexin 1 in regulating skeletal muscle and satellite cell function.

The development and regeneration of skeletal muscle are mediated by satellite cells (SCs), which ensure the efficient formation of myofibers while repopulating the niche that allows muscle repair following injuries. Pannexin 1 (Panx1) channels are expressed in SCs and their levels increase during differentiation in vitro, as well as during skeletal muscle development and regeneration in vivo. Panx1 has recently been shown to regulate muscle regeneration by promoting bleb-based myoblast migration and fusion. While skeletal muscle is largely influenced in a sex-specific way, the sex-dependent roles of Panx1 in regulating skeletal muscle and SC function remain to be investigated. Here, using global Panx1 knockout (KO) mice, we demonstrate that Panx1 loss reduces muscle fiber size and strength, decreases SC number, and alters early SC differentiation and myoblast fusion in male, but not in female mice. Interestingly, while both male and female Panx1 KO mice display an increase in the number of regenerating fibers following acute injury, the newly formed fibers in male Panx1 KO mice are smaller. Overall, our results demonstrate that Panx1 plays a significant role in regulating muscle development, regeneration, and SC number and function in male mice and reveal distinct sex-dependent functions of Panx1 in skeletal muscle.

Risk factors associated with Ctenocephalides felis flea infestation of peri-urban goats: a neglected parasite in an under-appreciated host.

Goats are critical in mixed smallholder agricultural systems in lower and middle-income countries, while fleas are important human and animal health concerns around the world. Convenience sampling was used to describe and consider risk factors for flea infestations of peri-urban goats, with the aim of informing the iterative development of animal husbandry and management based control strategies. Seven hundred and ninety-two goats were examined in 228 households across 10 peri-urban communities surrounding Blantyre in southern Malawi. The prevalence of Ctenocephalides felis fleas was 18.3, 37.1 and 100% at the levels of individual goats, households and communities, respectively, highlighting a neglected human and animal health concern. Constant introduction of new livestock coupled to a lack of biosecurity within communities, the ubiquitous presence of dog and cat hosts for C. felis, the frequency and thoroughness of cleaning overnight goat accommodation, and goat age less than 12 months old were identified as risk factors for flea infestation. This focal cross-sectional study highlights the significance of fleas in peri-urban communities and uncovers trends and commonalities that are needed to inform sustainable disease management. The majority of the peri-urban goat keepers were female, had resided in the same community throughout their whole life and had primary level education. Advice on the planned management of fleas in livestock needs to be tailored towards this demographic group. This approach affords an opportunity to promote public health measures to address household flea infestations and zoonotic disease spread.

Transcriptional and posttranscriptional regulation of the SMC-selective blood pressure-associated gene, ARHGAP42.

We previously showed that ARHGAP42 is a smooth muscle cell (SMC)-selective, RhoA-specific GTPase activating protein that regulates blood pressure and that a minor allele single nucleotide variation within a DNAse hypersensitive regulatory element in intron1 (Int1DHS) increased ARHGAP42 expression by promoting serum response factor binding. The goal of the current study was to identify additional transcriptional and posttranscriptional mechanisms that control ARHGAP42 expression. Using deletion/mutation, gel shift, and chromatin immunoprecipitation experiments, we showed that recombination signal binding protein for immunoglobulin κ-J region (RBPJ) and TEA domain family member 1 (TEAD1) binding to a conserved core region was required for full IntDHS transcriptional activity. Importantly, overexpression of the notch intracellular domain (NICD) or plating SMCs on recombinant jagged-1 increased IntDHS activity and endogenous ARHGAP42 expression while siRNA-mediated knockdown of TEAD1 inhibited ARHGAP42 mRNA levels. Re-chromatin immunoprecipitation experiments indicated that RBPJ and TEAD1 were bound to the Int1DHS enhancer at the same time, and coimmunoprecipitation assays indicated that these factors interacted physically. Our results also suggest TEAD1 and RBPJ bound cooperatively to the Int1DHS and that the presence of TEAD1 promoted the recruitment of NICD by RBPJ. Finally, we showed that ARHGAP42 expression was inhibited by micro-RNA 505 (miR505) which interacted with the ARHGAP42 3'-untranslated region (UTR) to facilitate its degradation and by AK124326, a long noncoding RNA that overlaps with the ARHGAP42 transcription start site on the opposite DNA strand. Since siRNA-mediated depletion of AK124326 was associated with increased H3K9 acetylation and RNA Pol-II binding at the ARHGAP42 gene, it is likely that AK124326 inhibits ARHGAP42 transcription.NEW & NOTEWORTHY First, RBPJ and TEAD1 converge at an intronic enhancer to regulate ARHGAP42 expression in SMCs. Second, TEAD1 and RBPJ interact physically and bind cooperatively to the ARHGAP42 enhancer. Third, miR505 interacts with the ARHGAP42 3'-UTR to facilitate its degradation. Finally, LncRNA, AK124326, inhibits ARHGAP42 transcription.

The utility of real-world evidence for benefit-risk assessment, communication, and evaluation of pharmaceuticals: Case studies.

PURPOSE: In recent years, novel types of real-world evidence (RWE) have played a role in various decision-making processes relating to medicinal products, including regulatory approval, patient access, health technology assessment, safety monitoring, clinical use, and post-approval lifecycle management. We therefore reviewed the potential utility of RWE in the cycle of medicinal product benefit-risk (BR) assessment, communication/risk minimization and evaluation ("BRACE"). METHODS: A convenience sample of illustrative studies was drawn from the published literature and examined. Specifically, we examined the purpose for using RWE, the type of RWE used, its novelty and how it might be integrated with other data and activities of the BRACE cycle, and how it contributed to regulatory decision-making. RESULTS: Eight studies were selected with each illustrating a different activity in the BRACE cycle ranging from BR assessment in the preapproval setting, post-approval assessment of safety or effectiveness, communicating BR information to patients and healthcare professionals, and evaluating the effectiveness of risk minimization initiatives to support a positive BR balance. CONCLUSIONS: RWE has an important role in informing regulatory decision-making regarding the BR management of medicines. With increasing digitalization, facilitating data collection and stakeholder engagement in health, this role is only expected to expand in the future. To reach the full potential of RWE, both regulators and sponsors will need to be familiar with a range of existing and emerging methods for generating and analyzing such evidence appropriately and achieve convergence regarding how different types of RWE can best be used to inform BR management and decision-making.

Improving the Accuracy of Newborn Weight Classification.

PURPOSE: The purpose of this project was to improve the accuracy of newborn weight classification using a regional newborn growth reference (Olsen), an evidence-based method, to determine SGA, AGA and LGA in term infants compared to the current growth reference (Lubchenco). DESIGN: Quality improvement methods using Lewin's Change Theory guided the process. SETTING/LOCAL PROBLEM: At an academic medical center term infants were evaluated for weight-for-gestational age using the Lubchenco growth reference as well as other growth references based on provider preference. PATIENTS: All term newborns (N = 314) admitted to the newborn nursery during one month following a 3-months implementation of the practice change. INTERVENTION/MEASUREMENTS: Newborn nursery nursing staff and provider staff were provided education and training on using and interpreting the new growth reference. RESULTS: Use of the Olsen regional growth reference identified more infants as small and fewer infants as large for gestational age. Post hoc analysis with a more global growth reference (Fenton) also identified more infants as small and fewer infants as large for gestational age. There was no statistically significant difference between the Olsen or Fenton growth references. CONCLUSION: Use of either of these two updated growth references more accurately classifies infant weight for gestational age compared to the Lubchenco growth reference, potentially decreasing newborn health risks such as hypoglycemia.

The relationship between early life stress and working memory in adulthood: A systematic review and meta-analysis.

Exposure to early life stress has been linked to impairment in cognitive functioning in adulthood. The aim of this study was to systematically review the literature on the relationship between early life stress and working memory, a central component of cognitive functioning. Database searches yielded 358 abstracts matching the search terms. Abstract screening followed by full-text review resulted in 26 publications suitable for inclusion, of which 23 were included in the meta-analysis. Results of the meta-analysis suggested exposure to early life stress was associated with poorer working memory. Even though there were a wide variety of working memory tasks used, this effect was significant for both phonological and visuospatial working memory tasks, and both visual and aural task presentation modalities. The effect was also found in samples with and without clinical psychopathology. This review provides recommendations for future research and implications for clinical practice.

Neither 'foolish' nor 'finished': identity control among older adults with HIV in rural Malawi.

Prevalence of HIV after age 50 is considerable, especially in southern Africa. Negative social constructions of HIV in older age, and the health consequences of ageing with the virus, mean that having HIV presents a challenge for many people's roles and social memberships, threatening to disrupt their sense of self. Using constructivist grounded theory and qualitative data from rural Malawi, this paper describes how older men and women deal with these identity challenges. Drawing on a symbolic interactionist framework, it uses identity control theory to explore how the study's participants presented their post-diagnosis behaviours in ways that maintained their most significant pre-diagnosis identities as 'adults', a label they gave to the core identity of being a person who belongs in the social world. Considering the processes through which older people with HIV navigated challenges to their identities in light of the intersectional influences of HIV and age-related stigma and illness, provides insight into how older people might experience HIV, as well as informing theoretical understandings of identity formation and maintenance in light of chronic and/or stigmatising illness more broadly.

MEASUREMENT OF FATHER-CHILD ROUGH-AND-TUMBLE PLAY AND ITS RELATIONS TO CHILD BEHAVIOR.

Although there is increasing evidence of paternal influence on child outcomes such as language and cognition, researchers are not yet clear on the features of father-child play that are most valuable in terms of child development. Physical play such as rough and tumble play (RTP) is a favored type of father-child play in Western societies that has been linked to children's socioemotional competence. It is important, therefore, to determine the implications of this play for child development. In this review and meta-analysis, associations between father-child physical play and child behavior were examined. The review also focused on study methods. Sixteen studies are reviewed, N = 1,521 father-child dyads, 35% boys. Study characteristics such as definitions of physical play, play settings, play measures, and coding were examined. The meta-analysis found weak to moderate population effects for links between father-child physical play and child aggression, social competence, emotional skills, and self-regulation. Research investigating the effect of father-child physical play on children's development will be improved when definitions clearly identify the nature of play, settings facilitate boisterous play, and measures include frequency and quality of play interactions. This play shows promise as an enhancer of positive father-child relationships and a catalyst for child development.

Association of Traumatic Brain Injury and Glioblastoma Multiforme: A Case Series.

Glioblastoma multiforme (GBM) is an aggressive variant of central nervous system gliomas that carries a dismal prognosis. Although GBM is the most frequently occurring and malignant type of glioma accounting for more than 60% of all brain tumors in adults, its overall incidence is rare, occurring at a rate of 3.21 per 100,000 persons. Little is known about the etiology of GBM, but one proposed theory is that GBM pathogenesis may be linked to a chronic inflammatory course initiated by traumatic injury to the brain. Limited case reports have suggested an association between GBMs and traumatic brain injury (TBI), but larger case-control and epidemiologic studies have been inconclusive. We present three service members (two active duty and one retired) who developed GBM near the original site of prior head trauma. Each service member's military occupation was in the special operations community and shared a common theme of TBI following head trauma/injury. The current research on the association between TBI and GBM is limited and conflicting, predominantly due to the low incidence of the disease in the general population. Evidence has indicated that TBI should be considered a chronic disease with long-term health impacts, including long-term disability, dementia, epilepsy, mental health conditions, and cardiovascular diseases. With the addition of our patients, as well as a recently published study proposing a molecular association between trauma and GBM, further research is needed to better understand the potential relationship.

CT imaging of intrauterine devices (IUD): expected findings, unexpected findings, and complications.

Intrauterine devices (IUDs) are a commonly used form of long-acting reversible contraception, which either contain copper or levonorgestrel to prevent pregnancy. Although symptomatic patients with indwelling IUDs may first undergo ultrasound to assess for device malposition and complications, IUDs are commonly encountered on CT in patients undergoing evaluation for unrelated indications. Frequently, IUD malposition and complications may be asymptomatic or clinically unsuspected. For these reasons, it is important for the radiologist to carefully scrutinize the IUD on any study in which it is encountered. To do so, the radiologist must recognize that normally positioned IUDs are located centrally within the uterine cavity. IUDs are extremely effective in preventing pregnancy, though inadvertent pregnancy risk is higher with malpositioned IUDs. Presence of fibroids or Mullerian abnormalities may preclude proper IUD placement. Radiologists play an important role in identifying complications when they arise and special considerations when planning for an IUD placement. There is a wide range of IUD malposition, affecting IUDs differently depending on the type of IUD and its mechanism of action. IUD malposition is the most common complication, but embedment and/or partial perforation can and can lead to difficulty when removed. Retained IUD fragments can result in continued contraceptive effect. Perforated IUDs do not typically cause intraperitoneal imaging findings.

Pannexin 1 dysregulation in Duchenne muscular dystrophy and its exacerbation of dystrophic features in mdx mice.

BACKGROUND: Duchenne muscular dystrophy (DMD) is associated with impaired muscle regeneration, progressive muscle weakness, damage, and wasting. While the cause of DMD is an X-linked loss of function mutation in the gene encoding dystrophin, the exact mechanisms that perpetuate the disease progression are unknown. Our laboratory has demonstrated that pannexin 1 (Panx1 in rodents; PANX1 in humans) is critical for the development, strength, and regeneration of male skeletal muscle. In normal skeletal muscle, Panx1 is part of a multiprotein complex with dystrophin. We and others have previously shown that Panx1 levels and channel activity are dysregulated in various mouse models of DMD. METHODS: We utilized myoblast cell lines derived from DMD patients to assess PANX1 expression and function. To investigate how Panx1 dysregulation contributes to DMD, we generated a dystrophic (mdx) mouse model that lacks Panx1 (Panx1-/-/mdx). In depth characterization of this model included histological analysis, as well as locomotor, and physiological tests such as muscle force and grip strength assessments. RESULTS: Here, we demonstrate that PANX1 levels and channel function are reduced in patient-derived DMD myoblast cell lines. Panx1-/-/mdx mice have a significantly reduced lifespan, and decreased body weight due to lean mass loss. Their tibialis anterior were more affected than their soleus muscles and displayed reduced mass, myofiber loss, increased centrally nucleated myofibers, and a lower number of muscle stem cells compared to that of Panx1+/+/mdx mice. These detrimental effects were associated with muscle and locomotor functional impairments. In vitro, PANX1 overexpression in patient-derived DMD myoblasts improved their differentiation and fusion. CONCLUSIONS: Collectively, our findings suggest that PANX1/Panx1 dysregulation in DMD exacerbates several aspects of the disease. Moreover, our results suggest a potential therapeutic benefit to increasing PANX1 levels in dystrophic muscles.

Comparison of interpersonal quality of contraceptive counseling delivered via telehealth versus in person.

OBJECTIVES: This study aimed to compare the interpersonal quality of contraceptive counseling between telehealth and in-person visits. STUDY DESIGN: Patients at a single Title X-funded clinic selected their preferred counseling modality (in person or telehealth via video or telephone) when scheduling an appointment for contraception. After counseling, we invited patients to complete a survey and recorded their desired contraceptive method. We assessed the quality of counseling using the Interpersonal Quality in Family Planning scale. We reviewed the electronic medical record to identify any subsequent clinician visit. We performed between-group comparisons using Mann-Whitney U, χ2, and Fisher exact tests. RESULTS: From March 2021 to June 2022, 360 patients were eligible to participate, and 296 (82%) completed the survey and were included in the analysis; 150 (51%) completed counseling in person, and 146 (49%) completed counseling via telehealth. In the telehealth group, 102 (70%) chose telephone, and 44 (30%) chose video. Respondent characteristics were similar between groups. The majority of respondents in both groups reported high quality of counseling, defined as a top score on the Interpersonal Quality in Family Planning scale (75.0% telehealth respondents and 80.0% in person, p = 0.30). Compared to respondents completing in-person counseling, telehealth respondents were less likely to have a subsequent clinician visit (89.0% versus 100.0%, p < 0.001). CONCLUSIONS: The majority of respondents reported high-quality contraceptive counseling without significant difference between the modalities. However, respondents choosing telehealth were less likely to have a subsequent clinician visit. Given the higher uptake of telephone compared to video, telehealth via telephone may be more accessible or acceptable to some patients. IMPLICATIONS: Contraceptive counseling via telehealth has similar high interpersonal quality when compared to traditional, in-person visits. However, barriers may exist for patients who choose telehealth contraceptive counseling to access subsequent in-person care. Utilization of telehealth for contraceptive visits may provide opportunities for more equitable health care and to expand contraceptive access.

Inhibition of PANX1 Channels Reduces the Malignant Properties of Human High-Risk Neuroblastoma.

Pannexin 1 (PANX1) is expressed in many tissue types including tissues of neural origin. Neuroblastoma (NB) is a neural crest-derived malignancy mainly occurring in children. The majority of NB patients present with high-risk disease for which current therapies are ineffective. Here, we show that while PANX1 is expressed in NB of all stages, high PANX1 expression in high-risk NB is associated with a reduced survival probability. PANX1 channel inhibition using probenecid (PBN) or carbenoxolone (CBX) reduced the proliferation of our panel of high-risk NB cell lines. We show that expression of the Y10F PANX1 mutant, which cannot be phosphorylated on tyrosine 10 and acts in a dominant-negative manner, curtailed NB cell proliferation. Furthermore, PBN and CBX treatment halted the growth of NB spheroids and in some cases triggered the regression of established NB spheroids. Finally, both drugs reduced the progression of high-risk NB in vivo. Together our data indicate that PANX1 channels regulate human NB malignant properties and that the use of PBN or CBX may provide a new therapeutic approach for high-risk NB.

Managing Cancer and Living Meaningfully (CALM): a qualitative study of a brief individual psychotherapy for individuals with advanced cancer.

BACKGROUND: Although psychosocial care has been regarded as central to palliative and supportive care, there have been few empirically tested approaches to individual intervention. AIM: The subjective experience of advanced cancer patients receiving a new manualized brief individual psychotherapy, referred to as Managing Cancer and Living Meaningfully (CALM), was examined prior to the initiation of a randomized controlled trial testing the effectiveness of this intervention. DESIGN: Semi-structured interviews were conducted with patients who had a diagnosis of advanced cancer, and who underwent the intervention. SETTING/PARTICIPANTS: Patients were recruited from a large urban regional cancer center in Toronto, Canada. The 10 interviewees included seven women and three men. All had completed between three to six CALM sessions prior to the interview. RESULTS: The CALM intervention was associated with profound and unique patient-identified benefits and no patient-identified risks or concerns. Five interrelated benefits of the intervention were identified: (1) a safe place to process the experience of advanced cancer; (2) permission to talk about death and dying; (3) assistance in managing the illness and navigating the healthcare system; (4) resolution of relational strain; and (5) an opportunity to 'be seen as a whole person' within the healthcare system. These benefits were regarded by participants as unique in their cancer journey. CONCLUSIONS: Findings from a qualitative study suggest that the CALM intervention provides substantial benefits for patients with advanced cancer prior to the end of life. Findings informed the development of a randomized controlled trial to evaluate the effectiveness of this intervention.

The Relationship between Father-Child Rough-and-Tumble Play and Children's Working Memory.

Rough-and-tumble play (RTP) between fathers and children has been linked to many social, emotional, and behavioural child outcomes, such as reduced aggression and increased self-regulation. This study extends our understanding of the importance of RTP to the development of the executive function, working memory. Father-child dyads (N = 30) were asked to play two RTP games that were videorecorded for later observational coding. Fathers were also asked to report the frequency with which they play RTP games with their child. Two measures of working memory were also collected. The working-memory index of the Wechsler Preschool and the Primary Scale of Intelligence-Fourth Edition were used to measure working-memory ability, and the working-memory subscale of the Behaviour Rating Inventory of Executive Function was used as a measure of working-memory problems. RTP frequency was associated with improved working-memory ability and fewer working-memory problems. RTP quality was associated with higher working-memory ability. This study adds to the growing evidence of the importance of father-child RTP for child development.