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The post-total laryngectomy airway poses perioperative challenges to anesthesia management. While endobronchial intubation is a cited complication, a low-lying stoma may increase this risk. Furthermore, the stoma’s proximity to a median sternotomy increases surgical and airway management complexity. This report highlights a case of endobronchial intubation in a patient with a low-lying stoma who presented for coronary artery bypass graft. With a stoma at the upper border of the sternum, intraoperative innovation was required to prevent endobronchial intubation while remaining out of the surgical field. This innovation may be useful in urgent surgical situations.

The objective of this study was to determine the effect of increasing hot carcass weight (HCW) on pork ham and belly processing characteristics. Pigs (n = 85) were slaughtered and divided into 3 HCW categories: Average (99 to 109 kg), Heavy (116 to 126 kg), and Very Heavy (134 to 144 kg). Fresh hams were fabricated and further processed as 3-piece (inside, outside, and knuckle) boneless cured hams. Fresh belly quality measurements were taken before bacon processing. Data were analyzed using the MIXED procedure in SAS including the main effect of weight class, with sex and sire line as random blocking effects. Means were considered significant at P ≤ 0.05. There were no differences (P = 0.08) in ham processing characteristics including pump uptake, retention, and cook yield. However, cured hams from heavier car- casses were less red and less yellow (P < 0.01). Heavier carcasses produced longer, thicker, and wider bellies (P < 0.01), but bellies did not differ in firmness (P = 0.16). Despite reduced pump uptake (P < 0.01), bellies from heavier carcasses had greater cooked yield than those from lighter carcasses (P < 0.01). Total area of sliced bacon increased with increasing carcass weight. Bacon slice lean area percentage decreased (P < 0.01) in bacon from Very Heavy carcasses compared to lighter carcasses. Iodine value was decreased (P = 0.04) approximately 2.5 units from 68.6 in fresh bellies from Average carcasses to 66.2 in bellies from Very Heavy carcasses. Overall, processing characteristics of hams and bellies were not impaired at heavier carcass weights, though the consumer acceptability of larger slices of bacon from heavier carcasses should be determined.

ABSTRACTBackground 3D printed implant surgical guides are designed to improve implant placement accuracy. However, they are a potential source of contamination during implant surgery and therefore require sterilization to prevent post-surgical infection. This study evaluated the effect that steam sterilizing 3D printed implant surgical guides has on the accuracy of fully guided implant placement.Methods 3D printed models were prepared with an edentulous site at the right maxillary central incisor. A surgical guide was designed and fabricated to place a bone level implant at this edentulous site. Ten implants were placed with surgical guides, followed by ten placed with the same guides after autoclave sterilization at 134°C for 6 minutes. Implants were scanned and analyzed using three-dimensional analysis software. The implant platform position, apex position, and angulation were evaluated before and after sterilization of the surgical guides.Results There were statistically significant deviations of implant platform and apex in the x-axis (bucco-lingual), y-axis (mesio-distal), and implant angulation (Wilcoxon signed-rank test, p

The objective was to characterize the effects of increasing carcass weight on pork carcass characteristics and yields from traditional and alternative fabrication methods, as well as evaluate the size of novel retail cuts. Pigs (n = 85) were slaughtered and divided into 3 hot carcass weight (HCW) categories: Average (99 to 109 kg), Heavy (116 to 126 kg), and Very Heavy (134 to 144 kg). Loin muscle area (LMA) and back fat depth were measured on all carcasses. Paired right and left sides were fabricated traditionally and alternatively (shoulder separation at the 4th/5th rib), respectively. From the alternative side, the serratus ventralis (SV) was removed from the cellar-trimmed butt, and the triceps brachii (TB) was removed from the picnic shoulder. All individual primals and subprimals were weighed for yield calculations. Data were analyzed using the MIXED procedure in SAS including the main effect of weight class, with sex and sire line as fixed blocking effects. Differences were considered significant at P ≤ 0.05. Regardless of fabrication method, whole primal and subprimal weights increased (P < 0.01) in heavier carcass weight classes compared with lighter classes, but when expressed as a percentage of chilled side weight, these increases did not often translate into meaningful differences in distribution of carcass weight. While the alternative shoulder-loin separation reduced loin and belly length, loins and bellies from heavier carcasses weighed more than those from carcasses typically produced in the U.S. pork industry today. Serratus ventralis weight was increased (P < 0.01) approximately 0.28 kg from Average to Very Heavy, while the TB weight was increased (P < 0.01) approximately 0.24 kg from Average to Very Heavy. At heavier weights, alternative fabrication of carcasses yielded novel cuts from the shoulder including the SV and TB that were of size to warrant further exploration as retail offerings.

Abstract Background Recent progress in cancer immunotherapy encourages the expansion of chimeric antigen receptor (CAR) T cell therapy in solid tumors including hepatocellular carcinoma (HCC). Overexpression of MET receptor tyrosine kinase is common in HCC; however, MET inhibitors are effective only when MET is in an active form, making patient stratification difficult. Specific MET-targeting CAR-T cells hold the promise of targeting HCC with MET overexpression regardless of signaling pathway activity. Methods MET-specific CARs with CD28ζ or 4-1BBζ as co-stimulation domains were constructed. MET-CAR-T cells derived from healthy subjects (HS) and HCC patients were evaluated for their killing activity and cytokine release against HCC cells with various MET activations in vitro, and for their tumor growth inhibition in orthotopic xenograft models in vivo. Results MET-CAR.CD28ζ and MET-CAR.4-1BBζ T cells derived from both HS and HCC patients specifically killed MET-positive HCC cells. When stimulated with MET-positive HCC cells in vitro, MET-CAR.CD28ζ T cells demonstrated a higher level of cytokine release and expression of programmed cell death protein 1 (PD-1) than MET-CAR.4-1BBζ T cells. When analyzed in vivo, MET-CAR.CD28ζ T cells more effectively inhibited HCC orthotopic tumor growth in mice when compared to MET-CAR.4-1BBζ T cells. Conclusion We generated and characterized MET-specific CAR-T cells for targeting HCC with MET overexpression regardless of MET activation. Compared with MET-CAR.4-1BBζ, MET-CAR.CD28ζ T cells showed a higher anti-HCC potency but also a higher level of T cell exhaustion. While MET-CAR.CD28ζ is preferred for further development, overcoming the exhaustion of MET-CAR-T cells is necessary to improve their therapeutic efficacy in vivo.

Soybean is one of the most economically important crops worldwide. However, soybean yield can be substantially decreased by many diseases. Soybean genotypes could have different reactions to pathogen infection. As a first step toward investigating the biochemical basis of soybean resistance and susceptibility to disease, phytochemicals in the seeds of 52 soybean genotypes previously reported to have different reactions to diseases of soybean rust (SBR), Phomopsis seed decay (PSD), and purple seed stain (PSS) were analyzed. Using GC-MS, a total of 46 compounds were tentatively identified which included 11 chemical groups. Among those, the major group was esters, followed by carboxylic acid, ketone, and sugar moieties. Compounds having reported antioxidant, anti-microbial, and anti-inflammatory activities were also identified. UHPLC-DAD/MS analysis indicated that there were five major isoflavone components presented in the samples, including daidzin, glycitin, genistin, malonyldaidzin, and malonylglycitin. Isoflavones have been reported to play an important role in defense from plant pathogens. Although there was variance in the isoflavone content among soybean genotypes, those with the SBR resistance Rpp6 gene (PI 567102B, PI 567104B, PI 567129) consistently exhibited the highest concentrations of daidzin, glycitin, genistin, and malonyldaidzin. The SBR resistant genotype, PI 230970 (Rpp2) had the greatest amount of genistin. The SBR resistant genotype, PI 200456 (Rpp5) resistant genotype uniquely contained glycitein, a compound that was absent in the other 51 genotypes examined. A PSD-resistant genotype PI 424324B had nearly four times the amount of stigmasterol as PI 556625, which was susceptible to SBR, PSD, and PSS in our previous tests. Results of this study provide useful information for further investigation of the biochemical basis of soybean resistance to diseases. The results may also aid in selection of soybean lines for breeding for resistance to soybean rust and other diseases.

Study Design Retrospective cohort. Purpose To determine (1) the effects of serotonin reuptake inhibitors in pseudarthrosis rates after anterior cervical decompression and fusion (ACDF) and (2) to identify patient-reported outcome measures in patients taking serotonin reuptake inhibitors. Overview of Literature Recent literature suggests that selective serotonin reuptake inhibitors (SSRIs) may inhibit fracture healing via downregulation of osteoblast differentiation. Spinal fusion supplementation with osteoblast-rich substances enhances spinal fusion, thus SSRIs may be detrimental. Methods Patients with 1-year postoperative dynamic cervical spine radiographs following ACDF were grouped into serotonin reuptake inhibitor prescriptions (SSRI, serotonin-norepinephrine reuptake inhibitor [SNRI], or tricyclic antidepressant [TCA]) and no prescription (atypical antidepressant or no antidepressant). Pseudarthrosis was defined as ≥1 mm interspinous process motion on dynamic radiographs. Logistic regression models were controlled for confounding to analyze pseudarthrosis rates. Alpha was set at p-values of

Abstract Background Due to relatively low malaria parasitaemia in pregnancy, an appropriate field test that can adequately detect infections in pregnant women presenting with illness or for malaria screening during antenatal care is crucially important. The objective was to evaluate the diagnostic accuracy of loop-mediated isothermal amplification (LAMP) for the detection of uncomplicated malaria in pregnancy. Methods This was a meta-analysis of diagnostic accuracy. Relevant studies that assessed the diagnostic performance of LAMP for the detection of malaria in pregnancy were searched in health-related electronic databases including PubMed, Ovid, and Google Scholar. The methodological quality of the studies included was evaluated using the QUADAS-2 tool. Results Of the 372 studies identified, eight studies involving 2999 pregnant women in five endemic countries that assessed the accuracy of LAMP were identified. With three types of PCR as reference tests, the pooled sensitivity of LAMP was 91% (95%CI 67–98%) and pooled specificity was 99% (95%CI 83–100%, 4 studies), and the negative likelihood ratio was 9% (2–40%). Caution is needed in the interpretation as there was substantial between-study heterogeneity (I 2: 80%), and a low probability that a person without infection is tested negative. With microscopy as a reference, the pooled sensitivity of LAMP was 95% (95%CI 26–100%) and pooled specificity was 100% (95%CI 94–100%, 4 studies). There was a wide range of sensitivity and substantial between-study heterogeneity (I 2 : 83.5–98.4%). To investigate the source of heterogeneity, a meta-regression analysis was performed with covariates. Of these potential confounding factors, reference test (p: 0.03) and study design (p:0.03) had affected the diagnostic accuracy of LAMP in malaria in pregnancy. Overall, there was a low certainty of the evidence in accuracy estimates. Conclusion The findings suggest that LAMP is more sensitive than traditional tests used at facilities, but the utility of detecting and treating these low-density infections is not well understood. Due to the limited number of studies with bias in their methodological quality, variation in the study design, and different types of reference tests further research is likely to change the estimate. Well-conceived large prospective studies with blinding of the index test results are recommenced.

Abstract Commercially cultivated Limnospira (species formerly classified to genus Arthrospira) is a popular food/supplement consumed by millions of people worldwide for health benefits. The objective of the current research was to advance the standardization technology for Limnospira. Quantitative methods were established to detect fatty acids as potential chemical markers and immune-enhancing activity. Analysis of 20 different batches of biomass obtained from one commercial grower demonstrated that there was a statistically significant relationship between the sum of two fatty acids (linoleic and γ-linolenic) and Toll-like receptor (TLR)2/TLR1-dependent activation (R 2 = 0.48, p = 0.0007). Investigation of 12 biomass samples sourced from growers in 10 different countries demonstrated that fatty acid content was again significantly correlated with biological activity (R 2 = 0.72, p = 0.0005) and the content of fatty acids varied by twofold and activity by 12.5-fold. This large variation between different samples confirms the need to use the present standardization methods to ensure consistent and properly characterized biomass for consumers and for future scientific research.

Key Clinical Message Serotonin syndrome can be a life‐threatening condition that occurs from the overactivity of serotonin in the central nervous system. This report describes the use of cyproheptadine for the management of serotonin syndrome in a patient taking fluoxetine and bupropion, who received methylene blue for vasoplegia syndrome. A 61‐year‐old female taking fluoxetine and bupropion preoperatively was given a total of three doses of methylene blue 100 mg IV within a brief time frame during and after a planned coronary artery bypass graft surgery. Postoperatively, the patient was not following commands, was agitated and confused, febrile with diaphoresis, tachycardic, had muscle rigidity, and horizontal ocular clonus. The patient's presentation was most consistent with serotonin syndrome due to a drug–drug interaction. Cyproheptadine and supportive care were used successfully to treat serotonin syndrome, and the patient was discharged home 14 days postoperatively. Based on the literature, there is no standardized method of weaning cyproheptadine when used for serotonin syndrome. The patient in our case received a total of 188 mg of cyproheptadine over the course of 10 days and did not experience any side effects. This case highlights a potential dosing regimen that can be used for other patients.

Oxidosqualene cyclases (OSCs) are the key enzymes accountable for the cyclization of 2,3-oxidosqualene to varied triterpenoids and phytosterols. Hoodia gordonii (from the family Apocynaceae), a native of the Kalahari deserts of South Africa, Namibia, and Botswana, is being sold as a prevalent herbal supplement for weight loss. The appetite suppressant properties are attributed to P57AS3, an oxypregnane steroidal glycoside. At the molecular level, the enzymes involved in the biosynthesis of triterpenes and phytosterols from H. gordonii have not been previously reported. In the current study, predicted transcripts potentially encoding oxidosqualene cyclases were recognized first by searching publicly available H. gordonii RNA-seq datasets. Two OSC-like sequences were selected for functional analysis. A monofunctional OSC, designated HgOSC1 which encodes lupeol synthase, and HgOSC2, a multifunctional cycloartenol synthase forming cycloartenol and other products, were observed through recombinant enzyme studies. These studies revealed that distinct OSCs exist for triterpene formation in H. gordonii and provided opportunities for the metabolic engineering of specific precursors in producing phytosterols in this plant species.

Catholic entities are being sued for personal injury compensation arising from sexual abuse perpetrated by church personnel. In some jurisdictions, the situation has deteriorated because of changes to the statute of limitations, the naming of an entity to sue, the setting aside of previous settlements, and abuse compensation law firms. Oftentimes there are overstated, doubtful or apparently false claims, and disturbing decisions. There is a feeling of being cornered with minimal prospects for change. How and what does the Church communicate when its predicament is frequently not ‘right and just?’ This article scrutinizes such powerlessness using the Magisterium of the Catholic Church on the truth of social communications. The Church insists on a proper understanding of truth and its uses. Despite the new adverse realities, the Church’s responses should communicate the truth in love. The article begins an analysis of various factors and recent changes causing the Church to find itself in a no-win situation. Next, several significant yet alternative perspectives are presented. Finally, there is an investigation of the magisterial teachings of the Catholic Church on the truth of social communications which offer a theological context to rethink the Church’s current circumstances.

Aims:: The terminology of obstetric pelvic floor disorders should be defined and reported as part of a wider clinically oriented consensus. Methods:: This Report combines the input of members of two International Organizations, the International Continence Society (ICS) and the International Urogynecological Association (IUGA). The process was supported by external referees. Appropriate clinical categories and a sub-classification were developed to give coding to definitions. An extensive process of 12 main rounds of internal and 2 rounds of external review was involved to exhaustively examine each definition, with decision-making by consensus. Results:: A terminology report for obstetric pelvic floor disorders, encompassing 357 separate definitions, has been developed. It is clinically-based with the most common diagnoses defined. Clarity and user-friendliness have been key aims to make it usable by different specialty groups and disciplines involved in the study and management of pregnancy, childbirth and female pelvic floor disorders. Clinical assessment, investigations, diagnosis, conservative and surgical treatments are major components. Illustrations have been included to supplement and clarify the text. Emerging concepts, in use in the literature and offering further research potential but requiring further validation, have been included as an appendix. As with similar reports, interval (5–10 year) review is anticipated to maintain relevance of the document and ensure it remains as widely applicable as possible. Conclusion:: A consensus-based Terminology Report for obstetric pelvic floor disorders has been produced to support clinical practice and research.

Abstract Background The consequences for children born with birth defects and developmental disabilities encompassed by foetal alcohol spectrum disorder (FASD) are profound, affecting all areas of social, behavioural and cognitive functioning. Given the strong evidence for a core deficit in executive functioning, underpinned by impaired self‐regulation skills, there has been a growing focus on the development of interventions that enhance or support the development of executive functions (EFs). Objectives The primary objective of this review is to synthesise the evidence for structured psychological interventions that explicitly aim to improve EF in children. The review also sought to ascertain if the effectiveness of interventions were influenced by characteristics of the intervention, participants or type of EF targeted by the intervention. Search Methods Sixteen databases, 18 grey literature search locations and 9 trial registries were systematically searched to locate eligible studies (up to December 2020). These searches were supplemented with reference harvesting, forward citation searching, hand searches of topic‐relevant journals and contact with experts. Selection Criteria Studies were included in the review if they reported on an impact evaluation of a psychological intervention aiming to improve EF in children 3–16 years who either had confirmed prenatal alcohol exposure or a formal diagnosis falling under the umbrella term of FASDs. Eligible study designs included randomised controlled trials (RCTs) and quasi‐experimental designs with either no treatment, wait list control or an alternative treatment as a comparison condition. Single‐group pre‐post designs were also included. Data Collection and Analysis Standard methodological procedures expected by the Campbell Collaboration were used at all stages of this review. Standardised mean differences (SMDs) were used to estimate intervention effects, which were combined with random effects meta‐analysis (data permitting). Risk of bias was assessed using the Cochrane Risk of Bias Tool (RoB2) and Cochrane Risk of Bias in Non‐Randomised Studies‐Interventions tool (ROBINS‐I). Main Results The systematic search identified 3820 unique records. After title/abstract and full‐text screening, 11 eligible studies (reported in 21 eligible documents) were deemed eligible, with a combined 253 participants. Of the 11 studies, 6 were RCTs, 1 was a quasi‐experiment and 4 were single‐group pre‐post intervention designs. All studies were rated as having an overall high or serious risk of bias, with some variation across domains for RCTs. For RCT and quasi‐experimental studies, the overall effect of EF interventions on direct and indirect measures of EF generally favoured the experimental condition, but was not statistically significant. There was no difference between intervention and comparison groups on direct measures of auditory attention (k = 3; SMD = 0.06, 95% confidence interval [CI] = −1.06, 1.18), visual attention (k = 2; SMD = 0.90, 95% CI = −1.41, 3.21), cognitive flexibility (k = 2; SMD = 0.23, 95% CI = −0.40, 0.86), attentional inhibition (k = 2; SMD = 0.04, 95% CI = −0.58, 0.65), response inhibition (k = 3; SMD = 0.47, 95% CI = −0.04, 0.99), or verbal working memory (k = 1; d = 0.6827; 95% CI = −0.0196, 1.385). Significant heterogeneity was found across studies on measures of auditory attention and visual attention, but not for measures of cognitive flexibility, attentional inhibition or response inhibition. Available data prohibited further exploration of heterogeneity. There was no statistical difference between intervention and comparison groups on indirect measures of global executive functioning (k = 2; SMD = 0.21, 95% CI = −0.40, 0.82), behavioural regulation (k = 2; SMD = 0.18, 95% CI = −0.43, 0.79), or emotional control (k = 3; SMD = 0.01, 95% CI = −0.33, 0.36). Effect sizes were positive and not significant for meta‐cognition (k = 1; SMD = 0.23, 95% CI = −0.72, 1.19), shifting (k = 2; SMD = 0.04, 95% CI = −0.35, 0.43), initiation (k = 1; SMD = 0.04, 95% CI = −0.40, 0.49), monitoring (k = 1; SMD = 0.25, 95% CI = −0.20, 0.70) and organisation of materials (k = 1; SMD = 0.25, 95% CI = −0.19, 0.70). Effect sizes were negative and not statistically different for effortful control (k = 1; SMD = −0.53, 95% CI = −1.50, 0.45), inhibition (k = 2; SMD = −0.08, 95% CI = −0.47, 0.31), working memory (k = 1; SMD = 0.00, 95% CI = −0.45, 0.44), and planning and organisation (k = 1; SMD = −0.10, 95% CI = −0.55, 0.34). No statistically significant heterogeneity was found for any of the syntheses of indirect measures of EF. Based on pre‐post single‐group designs, there was evidence for small to medium sized improvements in EF based on direct measures (cognitive flexibility, verbal working memory and visual working memory) and indirect measures (behavioural regulation, shifting, inhibition and meta‐cognition). However, these results must be interpreted with caution due to high risk of bias. Authors' Conclusions This review found limited and uncertain evidence for the effectiveness of interventions for improving executive functioning in children with FASD across 8 direct and 13 indirect measures of EF. The findings are limited by the small number of high‐quality studies that could be synthesised by meta‐analysis and the very small sample sizes for the included studies.

Background: The coronavirus disease-2019 (COVID-19) pandemic significantly affected management of cardiovascular disease around the world. The effect of the pandemic on volume of cardiovascular diagnostic procedures is not known. Objectives: This study sought to evaluate the effects of the early phase of the COVID-19 pandemic on cardiovascular diagnostic procedures and safety practices in Asia. Methods: The International Atomic Energy Agency conducted a worldwide survey to assess changes in cardiovascular procedure volume and safety practices caused by COVID-19. Testing volumes were reported for March 2020 and April 2020 and were compared to those from March 2019. Data from 180 centers across 33 Asian countries were grouped into 4 subregions for comparison. Results: Procedure volumes decreased by 47% from March 2019 to March 2020, showing recovery from March 2020 to April 2020 in Eastern Asia, particularly in China. The majority of centers cancelled outpatient activities and increased time per study. Practice changes included implementing physical distancing and restricting visitors. Although COVID testing was not commonly performed, it was conducted in one-third of facilities in Eastern Asia. The most severe reductions in procedure volumes were observed in lower-income countries, where volumes decreased 81% from March 2019 to April 2020. Conclusions: The COVID-19 pandemic in Asia caused significant reductions in cardiovascular diagnostic procedures, particularly in low-income countries. Further studies on effects of COVID-19 on cardiovascular outcomes and changes in care delivery are warranted.

The parable of the Prodigal Son in Luke 15 elicits profound responses and emotions in various times, places, and cultures. Why has it stood the test of time as one of Jesus’ most famous parables? One possible answer is that the story carries enduring appeal because of the underlying structure of the parable, a recurring pattern in literature called the monomyth. Peeling back the layers of the parable, one may uncover the foundational archetypes of the parable that make it timeless. Hidden significance of the parable may be illuminated by comparing its narrative to the hero quest of Joseph Campbell and the monomyth archetypes of Northrop Frye and Leland Ryken, both of which emphasize a cyclical movement that unifies all of literature. Also important are the specific archetypes within the general monomyth archetype, such as father and mother, bread and water. The parable also contains the four elements (mythoi) of the circular monomyth: romance, tragedy, anti-romance, and comedy. Using archetypal and myth criticism, this article demonstrates that the parable has enduring attraction because its underlying archetypes appeal to a deep layer of the human psyche and to what is elemental to the human experience.

In recent years, the popularity of copaiba oil-resin has increased worldwide due to its medicinal value and wide applications in industry. Despite its popularity, the oil has not been standardized by industry or regulatory agencies. Product adulteration in order to maximize profits has become a problem. To address these issues, the current study describes the chemical and chemometric characterization of forty copaiba oil-resin samples by GC/MS. The results demonstrated, with the exception of commercial samples, that all sample groups contained six characteristic compounds (β-caryophyllene, α-copaene, trans-α-bergamotene, α-humulene, γ-muurolene, and β-bisabolene) in varying concentrations. Furthermore, compositional patterns were observed in individual groups which corresponded to sample origin. Within the commercial group, two samples did not contain or contained only one of the characteristic compounds. Principal component analysis (PCA) revealed distinct groups which largely corresponded to sample origin. Moreover, commercial samples were detected by PCA as outliers, and formed a group far removed from the other samples. These samples were further subjected to analysis using a SFC/MS method. Product adulteration with soybean oil was clearly detected, with each individual triglyceride in soybean oil being unambiguously identified. By combining these analytical techniques, the overall quality of copaiba oil-resin can be assessed.

Background This study aimed to evaluate the effects of hypercarbia on arterial oxygenation during one-lung ventilation (OLV). Methods Fifty adult patients undergoing elective video-assisted thoracoscopic lobectomy or pneumonectomy were enrolled. Group I patients (n = 25) were first maintained at normocarbia (PaCO2: 38–42 mmHg) for 30 min and then at hypercarbia (45–50 mmHg). In Group II patients (n = 25), PaCO2 was maintained in the reverse order. Arterial oxygen partial pressure (PaO2), respiratory variables, hemodynamic variables, and hemoglobin concentration were compared during normocarbia and hypercarbia. Arterial O2 content and O2 delivery were calculated. Results PaO2 values during normocarbia and hypercarbia were 66.5 ± 10.6 and 79.7 ± 17.3 mmHg, respectively (mean difference: 13.2 mmHg, 95% CI for difference of means: 17.0 to 9.3, P < 0.001). SaO2 values during normocarbia and hypercarbia were 92.5 ± 4.8% and 94.3 ± 3.1% (P = 0.009), respectively. Static compliance of the lung (33.0 ± 5.4 vs. 30.4 ± 5.3 ml/cmH2O, P < 0.001), arterial O2 content (15.4 ± 1.4 vs. 14.9 ± 1.5 ml/dl, P < 0.001) and O2 delivery (69.9 ± 18.4 vs. 65.1 ± 18.1 ml/min, P < 0.001) were significantly higher during hypercarbia than during normocarbia. Conclusions Hypercarbia increases PaO2 and O2 carrying capacity and improves pulmonary mechanics during OLV, suggesting that it may help manage oxygenation during OLV. Therefore, permissive hypercarbia may be a simple and valuable modality to manage arterial oxygenation during OLV.

Abstract Aims Heart failure (HF) and type 2 diabetes (T2D), common co‐morbidities, translate into worse patient prognoses and higher direct costs than for either condition alone. Empagliflozin has been shown to markedly reduce cardiovascular (CV) deaths and HF hospitalizations (HHF) in HF patients with T2D. This study evaluated the lifetime cost‐effectiveness of supplementing standard of care (SoC) with empagliflozin, relative to SoC alone, in HF patients with T2D from the UK payer perspective. Methods and results An existing discrete‐event simulation model was adapted for the economic evaluation. Risk equations developed from time‐dependent parametric survival analyses using patient‐level HF subpopulation data from the EMPA‐REG OUTCOME trial were employed to predict CV and renal events. Non‐CV death, utility weights, and costs were drawn from UK sources. Quality‐adjusted life years (QALYs) and costs were discounted at 3.5% per annum. Relative to SoC, empagliflozin with SoC yielded fewer first HHF, recurrent HHF, CV death, and non‐fatal myocardial infarction but more non‐fatal stroke events. Empagliflozin with SoC vs. SoC alone was associated with increased average life expectancy (10.80 vs. 9.59 LYs) and quality of life (6.27 vs. 5.62 QALYs), though at higher lifetime cost (£18 197 vs. £16 829) per person, resulting in an incremental cost‐effectiveness ratio of £2093 per QALY. The probability of empagliflozin being cost‐effective in the HF subpopulation at a £20 000 per QALY willingness‐to‐pay threshold was 91%. Conclusions This analysis suggests that adding empagliflozin to SoC in HF patients with T2D constitutes a cost‐effective use of UK healthcare resources and may provide long‐term health benefits to patients.

This paper presents the application of machine vision and learning techniques to detect and identify the number of flower clusters on apple trees leading to the ability to predict the potential yield of apples. A new field robot was designed and built to collect and build a dataset of 1500 images of apples trees. The trained model produced a cluster precision of 0.88 or 88% and a percentage error of 14% over 106 trees running the mobile vehicle on both sides of the trees. The detection model was predicting less than the actual amount but the fruit flower count is still significant in that it can give the researcher information on the estimated growth and production of each tree with respect to the actions applied to each fruit tree. A bias could be included to compensate for the average undercount. The resulting F1-Score of the object detection model was 80%, which is similar to other research methods ranging from an F1-Score of 77.3% to 84.1%. This paper helps lay the foundation for future application of machine vision and learning techniques within apple orchards or other fruit tree settings.

Sample preparation remains both a challenging and time-consuming process in the field of bioanalytical chemistry. Many traditional techniques often require multi-step processes, which can introduce additional errors to the analytical method. Given the complexity of many biological matrices, thorough analyte extraction presents a major challenge to researchers. In the present study, a headspace solid-phase microextraction (HS-SPME) coupled with a GC/Q-ToF-MS method, was developed to quantify in vitro metabolism of β-caryophyllene by both human liver microsome (HLM) and S9 liver fractions. Validation of the method was demonstrated both in terms of linearity (R2 = 0.9948) and sensitivity with a limit of detection of 3 ng/mL and a limit of quantitation of 10 ng/mL. In addition, the method also demonstrated both inter- and intra-day precision with the relative standard deviation (RSD) being less than 10% with four concentrations ranging from 50–500 ng/mL. Since this method requires no solvents and minimal sample preparation, it provides a rapid and economical alternative to traditional extraction techniques. The method also eliminates the need to remove salts or buffers, which are commonly present in biological matrices. Although this method was developed to quantify in vitro metabolism of one analyte, it could easily be adapted to detect or quantify numerous volatiles and/or semi-volatiles found in biological matrices.

Academic scholarship has steadily reported unfavourable clinical findings on the sport of boxing, and national medical bodies have issued calls for restrictions on the sport. Yet, the positions taken on boxing by medical bodies have been subject to serious discussions. Beyond the medical and legal writings, there is also literature referring to the social and cultural features of boxing as ethically significant. However, what is missing in the bioethical literature is an understanding of the boxers themselves. This is apart from their brain injuries, the debates about the degenerative brain disease known as chronic traumatic encephalopathy (CTE), and related issues about the disease. This article argues that the lives of boxers, their relationships, their careers, and their futures, also requires its own research, particularly in telling stories about their lives, and those lives and futures which boxing affects. The article uses two approaches. First, to imagine a more enduring “whole of life viewpoint” by using an extended future timeframe. Second, to consider perspectives of a person’s significant others. After reviewing the boxing literature, the article discusses social settings and then explores the hidden social relationships in life after boxing. With these longer time and close relationship viewpoints, three important themes emerge: family and kinship; age, stage and career; and the effects of boxing fatalities. These analyses are used in conjunction with relevant clinical findings. which complement the telling of stories to improve medical information, and engages professional and public empathy for people’s experience of illness and difficulties in coping.

Bacteria with multiple drug resistance (MDR) have become a global issue worldwide, and hundreds of thousands of people’s lives are threatened every year. The emergence of novel MDR strains and insufficient development of new antimicrobial agents are the major reasons that limit the choice of antibiotics for the treatment of bacterial infection. Thus, preserving the clinical value of current antibiotics could be one of the effective approaches to resolve this problem. Here we identified numerous novel small RNAs that were downregulated in the MDR clinical isolates of Pseudomonas aeruginosa (P. aeru), and we demonstrated that overexpression of one of these small RNAs (sRNAs), AS1974, was able to transform the MDR clinical strain to drug hypersusceptibility. AS1974 is the master regulator to moderate the expression of several drug resistance pathways, including membrane transporters and biofilm-associated antibiotic-resistant genes, and its expression is regulated by the methylation sites located at the 5′ UTR of the gene. Our findings unravel the sRNA that regulates the MDR pathways in clinical isolates of P. aeru. Moreover, transforming bacterial drug resistance to hypersusceptibility using sRNA could be the potential approach for tackling MDR bacteria in the future.

Members of the genus Salvia are used as culinary herbs and are prized for their purported medicinal attributes. Since physiological effects can vary widely between species of Salvia, it is of great importance to accurately identify botanical material to ensure safety for consumers. In the present study, an in-depth chemical investigation is performed utilizing GC/Q-ToF combined with chemometrics. Twenty-four authentic plant samples representing five commonly used Salvia species, viz. S. apiana, S. divinorum, S. mellifera, S. miltiorrhiza, and S. officinalis, are analyzed using a GC/Q-ToF technique. High-resolution spectral data are employed to construct a sample class prediction (SCP) model followed by principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA). This model demonstrates 100% accuracy for both prediction and recognition abilities. Additionally, the marker compounds present in each species are identified. Furthermore, to reduce the time required and increase the confidence level for compound identification and the classification of different Salvia species, a personal compound database and library (PCDL) containing marker and characteristic compounds is constructed. By combining GC/Q-ToF, chemometrics, and PCDL, the unambiguous identification of Salvia botanicals is achieved. This high-throughput method can be utilized for species specificity and to probe the overall quality of various Salvia-based products.

Poison inhibitors of DNA topoisomerase II (TOP2) are clinically used drugs that cause cancer cell death by inducing DNA damage, which mechanism of action is also associated with serious side effects such as secondary malignancy and cardiotoxicity. In contrast, TOP2 catalytic inhibitors induce limited DNA damage, have low cytotoxicity, and are effective in suppressing cancer cell proliferation. They have been sought after to be prospective anticancer therapies. Herein the discovery of new TOP2 catalytic inhibitors is described. A new druggable pocket of TOP2 protein at its DNA binding domain was used as a docking site to virtually screen ~6 million molecules from the ZINC15 library. The lead compound, T60, was characterized to be a catalytic TOP2 inhibitor that binds TOP2 protein and disrupts TOP2 from interacting with DNA, resulting in no DNA cleavage. It has low cytotoxicity, but strongly inhibits cancer cell proliferation and xenograft growth. T60 also inhibits androgen receptor activity and prostate cancer cell growth. These results indicate that T60 is a promising candidate compound that can be further developed into new anticancer drugs.

Objective: To gather consumer perspectives of a mental health screening protocol and to identify the incidence of previously unrecognized mental health concerns (case finding). Design: Pilot study using mixed methods: quantitative (survey) and qualitative (interviews). Setting: Primary care health team in Kitchener, Ontario, Canada. Participants: Patients (N=15) with spinal cord injury living in the community. Participants ranged in age from 21 to 81 years of age (mean=46); 12 were men, 8 had tetraplegia and 5 paraplegia. The number of years since injury ranged from 1 to 32 (mean=13). Intervention: Implementation of a mental health screening protocol consisting of standardized screening tools for depression, anxiety, substance abuse, social isolation, somatoform disorder, functional status, chronic pain, and cognitive impairment. Main Outcome Measures: Positive results on screening tool, acceptability of the screening process, perceptions of the value of screening, and intentions to follow resulting treatment recommendations. Results: Screening identified 11 of 15 individuals with a chronic pain condition; 1 individual screened positive for depression, 1 for anxiety, 3 for potential substance abuse, and 1 for social isolation. Most of the participants (12/13) rated the screening protocol as very acceptable. All but 1 individual intended to follow resulting treatment recommendations. Interview analyses generated themes related to disclosure of experiences that were incomplete that concealed important information and perceptions that the screening protocol failed to assess resiliency. Although perceived as valuable, participants felt screening tools alone did not capture information important to them. Conclusions: Screening tools alone may not identify mental health issues. Interviews in addition to screening tools are needed to accurately identify mental health issues in this population. Identification of mental health issues is critical to ensuring access to effective interventions and improving health outcomes and quality of life for individuals with SCI. Keywords: Mental health, Rehabilitation, Screening, Spinal cord injuries

The Myc family of transcription factors are involved in the development and progression of numerous cancers, including prostate cancer (PCa). Under the pressure of androgen receptor (AR)-directed therapies resistance can occur, leading to the lethal form of PCa known as neuroendocrine prostate cancer (NEPC), characterized among other features by N-Myc overexpression. There are no clinically approved treatments for NEPC, translating into poor patient prognosis and survival. Therefore, there is a pressing need to develop novel therapeutic avenues to treat NEPC patients. In this study, we investigate the N-Myc-Max DNA binding domain (DBD) as a potential target for small molecule inhibitors and utilize computer-aided drug design (CADD) approaches to discover prospective hits. Through further exploration and optimization, a compound, VPC-70619, was identified with notable anti-N-Myc potency and strong antiproliferative activity against numerous N-Myc expressing cell lines, including those representing NEPC.

Abstract Background Rates of emergency hospitalisations are increasing in many countries, leading to disruption in the quality of care and increases in cost. Therefore, identifying strategies to reduce emergency admission rates is a key priority. There have been large-scale evidence reviews to address this issue; however, there have been no reviews of medication therapies, which have the potential to reduce the use of emergency health-care services. The objectives of this study were to review systematically the evidence to identify medications that affect emergency hospital admissions and prioritise therapies for quality measurement and improvement. Methods This was a systematic review of systematic reviews. We searched MEDLINE, PubMed, the Cochrane Database of Systematic Reviews & Database of Abstracts of Reviews of Effects, Google Scholar and the websites of ten major funding agencies and health charities, using broad search criteria. We included systematic reviews of randomised controlled trials that examined the effect of any medication on emergency hospital admissions among adults. We assessed the quality of reviews using AMSTAR. To prioritise therapies, we assessed the quality of trial evidence underpinning meta-analysed effect estimates and cross-referenced the evidence with clinical guidelines. Results We identified 140 systematic reviews, which included 1968 unique randomised controlled trials and 925,364 patients. Reviews contained 100 medications tested in 47 populations. We identified high-to moderate-quality evidence for 28 medications that reduced admissions. Of these medications, 11 were supported by clinical guidelines in the United States, the United Kingdom and Europe. These 11 therapies were for patients with heart failure (angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, aldosterone receptor antagonists and digoxin), stable coronary artery disease (intensive statin therapy), asthma exacerbations (early inhaled corticosteroids in the emergency department and anticholinergics), chronic obstructive pulmonary disease (long-acting muscarinic antagonists and long-acting beta-2 adrenoceptor agonists) and schizophrenia (second-generation antipsychotics and depot/maintenance antipsychotics). Conclusions We identified 11 medications supported by strong evidence and clinical guidelines that could be considered in quality monitoring and improvement strategies to help reduce emergency hospital admission rates. The findings are relevant to health systems with a large burden of chronic disease and those managing increasing pressures on acute health-care services.

Gemtuzumab ozogamicin (GO) is an anti-CD33 antibody-drug conjugate for the treatment of acute myeloid leukemia (AML). Although GO shows a narrow therapeutic window in early clinical studies, recent reports detailing a modified dosing regimen of GO can be safely combined with induction chemotherapy, and the combination provides significant survival benefits in AML patients. Here we tested whether the survival benefits seen with the combination arise from the enhanced reduction of chemoresidual disease and leukemic initiating cells (LICs). Herein, we use cell line and patient-derived xenograft (PDX) AML models to evaluate the combination of GO with daunorubicin and cytarabine (DA) induction chemotherapy on AML blast growth and animal survival. DA chemotherapy and GO as separate treatments reduced AML burden but left significant chemoresidual disease in multiple AML models. The combination of GO and DA chemotherapy eliminated nearly all AML burden and extended overall survival. In two small subsets of AML models, chemoresidual disease following DA chemotherapy displayed hallmark markers of leukemic LICs (CLL1 and CD34). In vivo, the two chemoresistant subpopulations (CLL1+/CD117− and CD34+/CD38+) showed higher ability to self-renewal than their counterpart subpopulations, respectively. CD33 was coexpressed in these functional LIC subpopulations. We demonstrate that the GO and DA induction chemotherapy combination more effectively eliminates LICs in AML PDX models than either single agent alone. These data suggest that the survival benefit seen by the combination of GO and induction chemotherapy, nonclinically and clinically, may be attributed to the enhanced reduction of LICs.

The use of copaiba oil has been reported since the 16th century in Amazon traditional medicine, especially as an anti-inflammatory ingredient and for wound healing. The use of copaiba oil continues today, and it is sold in various parts of the world, including the United States. Copaiba oil contains mainly sesquiterpenes, bioactive compounds that are popular for their positive effect on human health. As part of our ongoing research endeavors to identify the chemical constituents of broadly consumed herbal supplements or their adulterants, copaiba oil was investigated. In this regard, copaiba oil was subjected to repeated silica gel column chromatography to purify the compounds. As a result, one new and seven known sesquiterpenes/sesquiterpenoids were isolated and identified from the copaiba oil. The new compound was elucidated as (E)-2,6,10-trimethyldodec-8-en-2-ol. Structure elucidation was achieved by 1D- and 2D NMR and GC/Q-ToF mass spectral data analyses. The isolated chemical constituents in this study could be used as chemical markers to evaluate the safety or quality of copaiba oil.

Cardiac fibrosis is a common finding that is associated with the progression of heart failure (HF) and impacts all chambers of the heart. Despite intense research, the treatment of HF has primarily focused upon strategies to prevent cardiomyocyte remodeling, and there are no targeted antifibrotic strategies available to reverse cardiac fibrosis. Cardiac fibrosis is defined as an accumulation of extracellular matrix (ECM) proteins which stiffen the myocardium resulting in the deterioration cardiac function. This occurs in response to a wide range of mechanical and biochemical signals. Integrins are transmembrane cell adhesion receptors, that integrate signaling between cardiac fibroblasts and cardiomyocytes with the ECM by the communication of mechanical stress signals. Integrins play an important role in the development of pathological ECM deposition. This review will discuss the role of integrins in mechano-transduced cardiac fibrosis in response to disease throughout the myocardium. This review will also demonstrate the important role of integrins as both initiators of the fibrotic response, and modulators of fibrosis through their effect on cardiac fibroblast physiology across the various heart chambers.

Resistance to androgen-receptor (AR) directed therapies is, among other factors, associated with Myc transcription factors that are involved in development and progression of many cancers. Overexpression of N-Myc protein in prostate cancer (PCa) leads to its transformation to advanced neuroendocrine prostate cancer (NEPC) that currently has no approved treatments. N-Myc has a short half-life but acts as an NEPC stimulator when it is stabilized by forming a protective complex with Aurora A kinase (AURKA). Therefore, dual-inhibition of N-Myc and AURKA would be an attractive therapeutic avenue for NEPC. Following our computer-aided drug discovery approach, compounds exhibiting potent N-Myc specific inhibition and strong anti-proliferative activity against several N-Myc driven cell lines, were identified. Thereafter, we have developed dual inhibitors of N-Myc and AURKA through structure-based drug design approach by merging our novel N-Myc specific chemical scaffolds with fragments of known AURKA inhibitors. Favorable binding modes of the designed compounds to both N-Myc and AURKA target sites have been predicted by docking. A promising lead compound, 70812, demonstrated low-micromolar potency against both N-Myc and AURKA in vitro assays and effectively suppressed NEPC cell growth.

Abstract Cellulose microfibrils are synthesized by membrane‐embedded cellulose synthesis complexes (CSCs), currently modeled as hexamers of cellulose synthase (CESA) trimers. The three paralogous CESAs involved in secondary cell wall (SCW) cellulose biosynthesis in Arabidopsis (CESA4, CESA7, CESA8) are similar, but nonredundant, with all three isoforms required for assembly and function of the CSC. The molecular basis of protein–protein recognition among the isoforms is not well understood. To investigate the locations of the interfaces that are responsible for isoform recognition, we swapped three domains between the Arabidopsis CESAs required for SCW synthesis (CESA4, CESA7, and CESA8): N‐terminus, central domain containing the catalytic core, and C‐terminus. Chimeric genes with all pairwise permutations of the domains were tested for in vivo functionality within knockout mutant backgrounds of cesa4, cesa7, and cesa8. Immunoblotting with isoform‐specific antibodies confirmed the anticipated protein expression in transgenic plants. The percent recovery of stem height and crystalline cellulose content was assayed, as compared to wild type, the mutant background lines, and other controls. Retention of the native central domain was sufficient for CESA8 chimeras to function, with neither its N‐terminal nor C‐terminal domains required. The C‐terminal domain is required for class‐specific function of CESA4 and CESA7, and CESA7 also requires its own N‐terminus. Across all isoforms, the results indicate that the central domain, as well as the N‐ and C‐terminal regions, contributes to class‐specific function variously in Arabidopsis CESA4, CESA7, and CESA8.

The integrated information theory (IIT) proposes a quantitative measure, denoted as Φ, of the amount of integrated information in a physical system, which is postulated to have an identity relationship with consciousness. IIT predicts that the value of Φ estimated from brain activities represents the level of consciousness across phylogeny and functional states. Practical limitations, such as the explosive computational demands required to estimate Φ for real systems, have hindered its application to the brain and raised questions about the utility of IIT in general. To achieve practical relevance for studying the human brain, it will be beneficial to establish the reliable estimation of Φ from multichannel electroencephalogram (EEG) and define the relationship of Φ to EEG properties conventionally used to define states of consciousness. In this study, we introduce a practical method to estimate Φ from high-density (128-channel) EEG and determine the contribution of each channel to Φ. We examine the correlation of power, frequency, functional connectivity, and modularity of EEG with regional Φ in various states of consciousness as modulated by diverse anesthetics. We find that our approximation of Φ alone is insufficient to discriminate certain states of anesthesia. However, a multi-dimensional parameter space extended by four parameters related to Φ and EEG connectivity is able to differentiate all states of consciousness. The association of Φ with EEG connectivity during clinically defined anesthetic states represents a new practical approach to the application of IIT, which may be used to characterize various physiological (sleep), pharmacological (anesthesia), and pathological (coma) states of consciousness in the human brain.

This essay, written by the guest editor, is an introduction to a special issue of the Journal of Intelligence devoted to methodological issues associated with the Flynn Effect. The essay evaluates past Flynn Effect research in terms of exploratory versus confirmatory efforts. Future research is also cast within this same framework. Finally, the four special issue papers are briefly reviewed, including comments on their own exploratory/confirmatory status.

The World Health Organisation and International Society of Hypertension (WHO/ISH) cardiovascular disease (CVD) risk assessment charts have been implemented in many low- and middle-income countries as part of the WHO Package of Essential Non-Communicable Disease (PEN) Interventions for Primary Health Care in Low-Resource settings. Evaluation of the WHO/ISH cardiovascular risk charts and their use is a key priority and since they only existed in paper or PDF formats, we developed an R implementation of the charts for all epidemiological subregions of the world. The main strengths of this implementation are that it is built in a free, open-source, coding language with simple syntax, can be downloaded from github as a package (“whoishRisk”), and can be used with a standard computer.

Shiga toxins 1 and 2 (Stx1 and Stx2) from Shiga toxin-producing E. coli (STEC) bacteria were simultaneously detected with a newly developed, high-throughput antibody microarray platform. The proteinaceous toxins were immobilized and sandwiched between biorecognition elements (monoclonal antibodies) and pooled horseradish peroxidase (HRP)-conjugated monoclonal antibodies. Following the reaction of HRP with the precipitating chromogenic substrate (metal enhanced 3,3-diaminobenzidine tetrahydrochloride or DAB), the formation of a colored product was quantitatively measured with an inexpensive flatbed page scanner. The colorimetric ELISA microarray was demonstrated to detect Stx1 and Stx2 at levels as low as ~4.5 ng/mL within ~2 h of total assay time with a narrow linear dynamic range of ~1–2 orders of magnitude and saturation levels well above background. Stx1 and/or Stx2 produced by various strains of STEC were also detected following the treatment of cultured cells with mitomycin C (a toxin-inducing antibiotic) and/or B-PER (a cell-disrupting, protein extraction reagent). Semi-quantitative detection of Shiga toxins was demonstrated to be sporadic among various STEC strains following incubation with mitomycin C; however, further reaction with B-PER generally resulted in the detection of or increased detection of Stx1, relative to Stx2, produced by STECs inoculated into either axenic broth culture or culture broth containing ground beef.

The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a versatile RNA-binding protein playing a critical role in alternative pre-mRNA splicing regulation in cancer. Emerging data have implicated hnRNP A1 as a central player in a splicing regulatory circuit involving its direct transcriptional control by c-Myc oncoprotein and the production of the constitutively active ligand-independent alternative splice variant of androgen receptor, AR-V7, which promotes castration-resistant prostate cancer (CRPC). As there is an urgent need for effective CRPC drugs, targeting hnRNP A1 could, therefore, serve a dual purpose of preventing AR-V7 generation as well as reducing c-Myc transcriptional output. Herein, we report compound VPC-80051 as the first small molecule inhibitor of hnRNP A1 splicing activity discovered to date by using a computer-aided drug discovery approach. The inhibitor was developed to target the RNA-binding domain (RBD) of hnRNP A1. Further experimental evaluation demonstrated that VPC-80051 interacts directly with hnRNP A1 RBD and reduces AR-V7 messenger levels in 22Rv1 CRPC cell line. This study lays the groundwork for future structure-based development of more potent and selective small molecule inhibitors of hnRNP A1⁻RNA interactions aimed at altering the production of cancer-specific alternative splice isoforms.

Background: The purpose of this study was to explore family medicine residents’ perceptions of a newly restructured integrated longitudinal curriculum. Method: A purposeful sample of 16 family medicine residents participated in focus group interviews conducted from a grounded theory perspective to identify the characteristics of this training model that contribute to and that challenge learning. Results: Eight key themes were identified: continuity of care, relevance to family medicine, autonomy, program-focused preparation, professional development as facilitated by role modeling, patient volume, clarity of expectations for learners, and logistics. Positive learning experiences were marked by high levels of autonomy, continuity, and relevance to family medicine. Less favorable learning experiences were characterized by limited opportunities for continuity of care, limited relevance to family medicine practice and unclear expectations for the resident’s role. Family physician-led learning experiences contributed to residents’ understanding of the full scope of family medicine practice, more so than specialist-led experiences. The logistics of implementing the integrated block were challenging and negatively impacted continuity and learning. Conclusions: This study suggests that an integrated longitudinalized family medicine block training model has the potential to support the principles of a longitudinal integrated competency-based curriculum to effectively prepare residents for family medicine practice.

With the aging population, escalating demand for seniors’ care and limited specialist resources, new care delivery models are needed to improve capacity for primary health care for older adults. This paper describes the “C5-75” (Case-finding for Complex Chronic Conditions in Seniors 75+) program, an innovative care model aimed at identifying frailty and commonly associated geriatric conditions among older adults within a Canadian family practice setting and targeting interventions for identified conditions using a feasible, systematic, evidence-informed multi-disciplinary approach. We screen annually for frailty using gait speed and handgrip strength, screen for previously undiagnosed comorbid conditions, and offer frail older adults multi-faceted interventions that identify and address unrecognized medical and psychosocial needs. To date, we have assessed 965 older adults through this program; 14% were identified as frail based on gait speed alone, and 5% identified as frail based on gait speed with grip strength. The C5-75 program aims to re-conceptualize care from reactive interventions post-diagnosis for single disease states to a more proactive approach aimed at identifying older adults who are at highest risk of poor health outcomes, case-finding for unrecognized co-existing conditions, and targeting interventions to maintain health and well-being and potentially reduce vulnerability and health destabilization.

Background: There is limited understanding of the impact of Triple C competency-based curriculums on the preparation of residents for family practice. This paper describes a competency-based curriculum within an integrated longitudinal block design and presents preliminary evaluation data on the impact of this curriculum on preparedness for family practice. Methods: First and second year family medicine residents were surveyed as a component of a year-end program evaluation to assess the extent to which the residency program is preparing them to engage in a variety of practice domains, the likelihood that they would engage in these domains, and the extent to which this residency program is comprehensive, relevant to their development as a family physician, and promotes interprofessional practice. Results: Residents perceived themselves as prepared to engage in most practice areas and their intentions to engage in various practice domains were positively correlated to their ratings of preparedness. Ratings reflected that residents perceived this program as comprehensive and relevant to their development as a family physician and they perceived a high degree of encouragement for interprofessional practice. Conclusions: This study provides some preliminary evidence that an integrated competency-based curriculum, with an emphasis on interprofessional practice has the potential to effectively prepare residents for practice in family medicine.

Background: The consequences for children born with birth defects and developmental disabilities encompassed by foetal alcohol spectrum disorder (FASD) are profound, affecting all areas of social, behavioural and cognitive functioning. Given the strong evidence for a core deficit in executive functioning, underpinned by impaired self-regulation skills, there has been a growing focus on the development of interventions that enhance or support the development of executive functions (EFs). Objectives: The primary objective of this review is to synthesise the evidence for structured psychological interventions that explicitly aim to improve EF in children. The review also sought to ascertain if the effectiveness of interventions were influenced by characteristics of the intervention, participants or type of EF targeted by the intervention. Search Methods: Sixteen databases, 18 grey literature search locations and 9 trial registries were systematically searched to locate eligible studies (up to December 2020). These searches were supplemented with reference harvesting, forward citation searching, hand searches of topic-relevant journals and contact with experts. Selection Criteria: Studies were included in the review if they reported on an impact evaluation of a psychological intervention aiming to improve EF in children 3-16 years who either had confirmed prenatal alcohol exposure or a formal diagnosis falling under the umbrella term of FASDs. Eligible study designs included randomised controlled trials (RCTs) and quasi-experimental designs with either no treatment, wait list control or an alternative treatment as a comparison condition. Single-group pre-post designs were also included. Data Collection and Analysis: Standard methodological procedures expected by the Campbell Collaboration were used at all stages of this review. Standardised mean differences (SMDs) were used to estimate intervention effects, which were combined with random effects meta-analysis (data permitting). Risk of bias was assessed using the Cochrane Risk of Bias Tool (RoB2) and Cochrane Risk of Bias in Non-Randomised Studies-Interventions tool (ROBINS-I). Main Results: The systematic search identified 3820 unique records. After title/abstract and full-text screening, 11 eligible studies (reported in 21 eligible documents) were deemed eligible, with a combined 253 participants. Of the 11 studies, 6 were RCTs, 1 was a quasi-experiment and 4 were single-group pre-post intervention designs. All studies were rated as having an overall high or serious risk of bias, with some variation across domains for RCTs. For RCT and quasi-experimental studies, the overall effect of EF interventions on direct and indirect measures of EF generally favoured the experimental condition, but was not statistically significant. There was no difference between intervention and comparison groups on direct measures of auditory attention (k = 3; SMD = 0.06, 95% confidence interval [CI] = -1.06, 1.18), visual attention (k = 2; SMD = 0.90, 95% CI = -1.41, 3.21), cognitive flexibility (k = 2; SMD = 0.23, 95% CI = -0.40, 0.86), attentional inhibition (k = 2; SMD = 0.04, 95% CI = -0.58, 0.65), response inhibition (k = 3; SMD = 0.47, 95% CI = -0.04, 0.99), or verbal working memory (k = 1; d = 0.6827; 95% CI = -0.0196, 1.385). Significant heterogeneity was found across studies on measures of auditory attention and visual attention, but not for measures of cognitive flexibility, attentional inhibition or response inhibition. Available data prohibited further exploration of heterogeneity. There was no statistical difference between intervention and comparison groups on indirect measures of global executive functioning (k = 2; SMD = 0.21, 95% CI = -0.40, 0.82), behavioural regulation (k = 2; SMD = 0.18, 95% CI = -0.43, 0.79), or emotional control (k = 3; SMD = 0.01, 95% CI = -0.33, 0.36). Effect sizes were positive and not significant for meta-cognition (k = 1; SMD = 0.23, 95% CI = -0.72, 1.19), shifting (k = 2; SMD = 0.04, 95% CI = -0.35, 0.43), initiation (k = 1; SMD = 0.04, 95% CI = -0.40, 0.49), monitoring (k = 1; SMD = 0.25, 95% CI = -0.20, 0.70) and organisation of materials (k = 1; SMD = 0.25, 95% CI = -0.19, 0.70). Effect sizes were negative and not statistically different for effortful control (k = 1; SMD = -0.53, 95% CI = -1.50, 0.45), inhibition (k = 2; SMD = -0.08, 95% CI = -0.47, 0.31), working memory (k = 1; SMD = 0.00, 95% CI = -0.45, 0.44), and planning and organisation (k = 1; SMD = -0.10, 95% CI = -0.55, 0.34). No statistically significant heterogeneity was found for any of the syntheses of indirect measures of EF. Based on pre-post single-group designs, there was evidence for small to medium sized improvements in EF based on direct measures (cognitive flexibility, verbal working memory and visual working memory) and indirect measures (behavioural regulation, shifting, inhibition and meta-cognition). However, these results must be interpreted with caution due to high risk of bias. Authors' Conclusions: This review found limited and uncertain evidence for the effectiveness of interventions for improving executive functioning in children with FASD across 8 direct and 13 indirect measures of EF. The findings are limited by the small number of high-quality studies that could be synthesised by meta-analysis and the very small sample sizes for the included studies.