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CONTEXT The Modified Checklist for Autism in Toddlers, Revised with Follow-up (M-CHAT-R/F) is used worldwide to screen for autism spectrum disorder (ASD). OBJECTIVE To calculate psychometric properties of the M-CHAT-R/F for subsequent diagnosis of ASD. DATA SOURCES Systematic searches of Medline, Embase, SCOPUS, and Trip Pro databases from January 2014 to November 2021. STUDY SELECTION Studies were included if they (1) used the M-CHAT-R/F (2) applied standard scoring protocol, (3) used a diagnostic assessment for ASD, and (4) reported at least 1 psychometric property of the M-CHAT-R/F. DATA EXTRACTION Two independent reviewers completed screening, full-text review, data extraction, and quality assessment, following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A random-effects model was used to derive pooled estimates and assess for between-study heterogeneity. RESULTS Of 667 studies identified, 15 with 18 distinct samples from 10 countries (49 841 children) were used in the meta-analysis. Pooled positive predictive value (PPV), was 57.7% (95% confidence interval [CI] 48.6–66.8, τ2 = 0.031). PPV was higher among high-risk (75.6% [95% CI 66.0–85.2]) than low-risk samples (51.2% [95% CI 43.0–59.5]). Pooled negative predictive value was 72.5% (95% CI 62.5–82.4 τ2 = 0.031), sensitivity was 82.6% (95% CI 76.2–88.9) and specificity 45.7% (95% CI 25.0–66.4). LIMITATIONS Negative predictive value, sensitivity, and specificity were calculated based on small sample sizes because of limited or no evaluation of screen-negative children. CONCLUSIONS These results support use of the M-CHAT-R/F as a screening tool for ASD. Caregiver counseling regarding likelihood of an ASD diagnosis after positive screen should acknowledge the moderate PPV.

The following key questions and recommendations are presented herein: when is airway intubation initiated in severe trauma? Airway intubation must be initiated in severe trauma patients with a GCS of 8 or lower (1B). Should rapid sequence intubation (RSI) be performed in trauma patients? RSI should be performed in trauma patients to secure the airway unless it is determined that securing the airway will be problematic (1B). What should be used as an induction drug for airway intubation? Ketamine or etomidate can be used as a sedative induction drug when RSI is being performed in a trauma patient (2B). If cervical spine damage is suspected, how is cervical protection achieved during airway intubation? When intubating a patient with a cervical spine injury, the extraction collar can be temporarily removed while the neck is fixed and protected manually (1C). What alternative method should be used if securing the airway fails more than three times? If three or more attempts to intubate the airway fail, other methods should be considered to secure the airway (1B). Should trauma patients maintain normal ventilation after intubation? It is recommended that trauma patients who have undergone airway intubation maintain normal ventilation rather than hyperventilation or hypoventilation (1C). When should resuscitative thoracotomy be considered for trauma patients? Resuscitative thoracotomy is recommended for trauma patients with penetrating injuries undergoing cardiac arrest or shock in the emergency room (1B).

Essentials Exercise Limitation 1 year after an acute pulmonary embolism is common.Serial imaging after acute pulmonary embolism is not well described and how it affects exercise limitation remains unknown.1 year after an acute pulmonary embolism chronic changes are common, more so on perfusion lung scanning than CT pulmonary angiography, but imaging findings did not predict exercise limitation. Introduction Risk factors for exercise limitation after acute pulmonary embolism (PE) are unknown. As a planned sub‐study of the prospective, multicenter ELOPE (Evaluation of Long‐term Outcomes after PE) Study, we aimed to describe the results of serial imaging by computed tomography pulmonary angiography (CTPA) and perfusion scan during 1 year after a first episode of acute pulmonary embolism, and to assess the association between imaging parameters and exercise limitation at 1 year. Methods In a prospective cohort study, 100 patients were recruited between June 2010 and February 2013 at five Canadian university–affiliated hospitals. CT pulmonary angiography was performed at baseline and 12 months, perfusion scan at 6 and 12 months, and cardio‐pulmonary exercise testing at 1 and 12 months. Imaging parameters included: on CT pulmonary angiography, CT obstruction index (CTO) (% clot burden in the pulmonary vasculature), and on perfusion scan, pulmonary vascular obstruction (PVO) (% perfusion defect). Abnormal cardio‐pulmonary exercise test (primary outcome) was defined as percent of predicted peak oxygen uptake (VO2) 80% on 1‐year cardio‐pulmonary exercise testing (1.4% [0%; 5.7%] vs 1.0% [0%; 2.4%]; P = .70). Mean (SD) pulmonary vascular obstruction at 6 and at 12 months was similar in patients with percent‐predicted VO2 peak 80% (6 months: 5.9% [0%; 10.4%] vs 6.2% [4.5%; 9.0%]; P = .91; 12 months: 5.1% [0%; 10.2%] vs 6.0% [0%; 9.7%]; P = .71). Conclusions Imaging findings after pulmonary embolism did not predict exercise limitation. Residual thrombus does not appear to explain long‐term functional limitation after pulmonary embolism.

Unusual site deep vein thrombosis (USDVT) is an uncommon form of venous thromboembolism (VTE) with heterogeneity in pathophysiology and clinical features. While the need for anticoagulation treatment is generally accepted, there is little data on optimal USDVT treatment. The TRUST study aimed to characterize the epidemiology, treatment and outcomes of USDVT. From 2008 to 2012, 152 patients were prospectively enrolled at 4 Canadian centers. After baseline, patients were followed at 6, 12 and 24months. There were 97 (64%) cases of splanchnic, 33 (22%) cerebral, 14 (9%) jugular, 6 (4%) ovarian and 2 (1%) renal vein thrombosis. Mean age was 52.9years and 113 (74%) cases were symptomatic. Of 72 (47%) patients tested as part of clinical care, 22 (31%) were diagnosed with new thrombophilia. Of 138 patients evaluated in follow-up, 66 (48%) completed at least 6months of anticoagulation. Estrogen exposure or inflammatory conditions preceding USDVT were commonly associated with treatment discontinuation before 6months, while previous VTE was associated with continuing anticoagulation beyond 6months. During follow-up, there were 22 (16%) deaths (20 from cancer), 4 (3%) cases of recurrent VTE and no fatal bleeding events. Despite half of USDVT patients receiving6months of anticoagulation, the rate of VTE recurrence was low and anticoagulant treatment appears safe. Thrombophilia testing was common and thrombophilia prevalence was high. Further research is needed to determine the optimal investigation and management of USDVT.

Background Chronic obstructive pulmonary disease (COPD) is associated with poor prognosis and a high health care burden. The incidence of asthma and COPD overlap syndrome is increasing, and contributes to a high financial burden and poor prognosis. Objective To investigate clinical features of the overlap syndrome among Asian patients and to analyse its impact on hospitalisation due to respiratory problems or death compared to COPD alone. Design We performed a retrospective cohort analysis of 2933 COPD patients presenting at the Asan Medical Center from 1 January 2000 to 31 December 2009. Kaplan-Meier and Cox proportional hazard models were used to analyse the significance of clinical parameters, including age, sex, smoking history, body mass index (BMI), severity of airflow limitation, airway obstruction reversibility and overlap syndrome with hospitalisation due to respiratory problems or death. Results Overlap syndrome patients were older, included smaller proportions of males and of smokers and had lower forced expiratory volume in 1 s (FEV1) (% predicted). Shorter hospitalisation-free and survival periods were noted among overlap syndrome patients. Overlap syndrome was significantly associated with risk of hospitalisation due to respiratory problems after adjusting for age, smoking history, BMI, FEV1 (% predicted) and changes in FEV1 (P Conclusion Asthma and COPD overlap syndrome is associated with a higher risk of hospitalisation due to respiratory problems than COPD alone.

Background Treatment for advanced non-small-cell lung cancer (NSCLC), especially in patients with wild-type EGFR, remains limited. Recently, erlotinib, a tyrosine kinase inhibitor (TKI) targeting EGFR mutation, was approved as second-line treatment in EGFR wild-type NSCLC. Despite evidence of better overall survival (OS) with chemotherapy than with TKI in second-line treatment, data on the use of TKI in the real-life clinical setting remain limited. The present practice review of TKI use for second- and third-line treatment in EGFR wild-type NSCLC also compares clinical outcomes for TKI and single-agent docetaxel as second-line treatment. Methods Our retrospective cohort study included patients with EGFR wild-type NSCLC treated at the Jewish General Hospital (Montreal, QC) between 2003 and 2013. Patients received a TKI (erlotinib or gefitinib) in the second and third line or docetaxel in the second line. For each group, we determined OS, disease control rate, progression-free survival (PFS), and event-free survival (EFS). Results The TKI group included 145 patients, with 92 receiving second-line treatment. In the control group, 53 patients received docetaxel as second-line therapy. In the TKI group, OS was 6.0 months; PFS, 2.7 months; and EFS, 3.0 months. Comparing second-line treatments, OS was 5.3 and 5.0 months respectively (p = 0.88), PFS was 2.5 and 1.8 months respectively (p = 0.041), and EFS was 3.0 and 1.7 months respectively (p = 0.009). Conclusions In our study cohort, second-line therapy for EGFR wild-type NSCLC with TKI (compared with docetaxel) was associated with statistically better PFS and EFS and noninferior OS. Those findings raise the question of whether EFS should also be considered when choosing second-line treatment in this patient population.

Two studies were conducted to examine the influence of valence and extremity of consumer product reviews on attitude toward the brand and attitude toward the website. Each experiment was a one factor (valence/extremity: extremely negative, moderately negative, extremely positive) between-subjects design with a control group. Results in both studies showed that although extremely positive reviews increased attitude toward the brand, even a moderate amount of negativity negated this effect. Moreover, extremely negative reviews had a stronger influence on attitude toward the brand than either moderately negative reviews or extremely positive product reviews, thus supporting both negativity and extremity effect. Findings also show that varying degrees of brand review valence and extremity influenced attitude toward the website depending on website type (i.e., retailer vs. brand).

Two hundred and twenty-two children of divorce reported their reactions to stressful life events. They reported the threat posed by the events, self-blame, self-efficacy and negative emotions of sadness, anger and anxiety. Also, children's psychological maladjustment (Depression, Hostility and Anxiety) were assessed. As expected, the children's primary appraisal of threat was associated with all the negative emotions and psychological maladjustments. The role of children's secondary appraisals was confirmed by the findings that high self-blame for the stressful events was associated with the emotion of sadness, and low coping was associated with the psychological maladjustment of Anxiety. Finally, interactions between children's primary and secondary appraisals were observed: the emotions of anger and anxiety and the psychological maladjustments of Hostility and Anxiety increased with increases of self-blame when threat was low, but not when threat was high. The findings were discussed with respe...

A modified polyacrylamide gel electrophoresis system is described which provides excellent resolution of very high molecular weight proteins. This system has been successfully applied to the immunochemical detection of dystrophin in mouse and rat skeletal muscle, mouse myotubes in cell culture, and in human muscle-biopsy specimens. The mass of total homogenate protein (3-12 micrograms) and the relative quantity of dystrophin detected immunologically were found to be strongly correlated (r = 0.970 - 0.995). The method described here requires minute quantities of tissue or cells to accurately evaluate the relative amount of dystrophin present. The entire procedure for the detection of dystrophin is simple, rapid and cost efficient compared to other available techniques.

We report on a child with X-linked nephrogenic diabetes insipidus (NDI) who developed Wilms tumor (WT). Nephrogenic diabetes insipidus is caused by mutations of the arginine vasopressin receptor (AVPR2) or aquaporin-II (AQP2) genes. Wilms tumor is also genetically heterogeneous and is associated with mutations of WT1 (15-20%), WTX (20-30%) and other loci. The boy presented at 5 months with failure to thrive, polyuria, hypernatremia and abdominal mass. Analysis of leukocyte DNA showed a novel missense mutation (Q174H) of the AVPR2 gene, which was not present in his mother. In cells (WitS) isolated from the tumor, WTX mRNA expression and coding sequence were intact. However, we identified a 44-kb homozygous deletion of the WT1 gene spanning exons 4 to 10. The WT1 deletion was not present in leukocyte DNA from the patient or his mother. We also noted strong beta-catenin (CTNNB1) expression in the tumor cells and identified a heterozygote missense Ser45Cys mutation of exon 3 of CTNNB1. However, the mutation was absent both in the constitutional DNA of the patient and his mother. The concurrence of WT and NDI has not been previously reported and may be unrelated. Nevertheless, this case nicely illustrates the sequence of events leading to sporadic Wilms tumor.

e19147 Background: Wild-type NSCLC constitutes the large majority of lung cancers, but treatment is limited. Current standard for second-line treatment are pemetrexed, docetaxel or erlotinib. Few t...

The relative tissue content of dystrophin has been evaluated in the slow-twitch soleus (primarily type I fibers) and fast-twitch vastus lateralis (primarily type IIb filbers) muscles of the rat and mouse, as well as in human biopsy samples from the vastus lateralis and gluteus maximus muscles, using a sensitive immunochemical assay. The dystrophin content of the soleus muscle was approximately twofold higher than in the vastus lateralis muscle. This difference is not entirely explained by the higher total sarcolemmal surface of the smaller soleus muscle type I fibers, and is therefore attributed to a higher content of dystrophin in the type I fibers compared to type II fibers, PCR analysis of the dystrophin transcript levels in the two muscle types indicated no significant differences. Analysis of human muscle biopsies revealed a twofold higher dystrophin content in the vastus lateralis muscle compared to the gluteus maximum muscle. It is concluded that the tissue content of dystrophin may vary significantly among physiologically different skeletal muscle types.

Androgen receptor measurements with [3H]-methyltrienolone [17 beta-hydroxy-17 alpha-methyl-estra-4,9,11-trien-3-one (R1881)] or [3H]testosterone in vastus lateralis muscle cytosol of intact male rats yielded similar numbers of binding sites. Gonadectomy significantly increased the androgen receptor values, and both steroids gave similar results. The binding of [3H]-testosterone was not affected by adrenalectomy. In contrast, [3H]R1881 binding increased 2-fold after adrenalectomy. Competition experiments as well as sucrose density gradient analysis indicated that R1881, in addition to its binding of the androgen receptor, was also bound to glucocorticoid receptor. These results show that the synthetic androgen R1881 must be used with caution in tissues suspected to contain glucocorticoid receptors.

The process of muscular atrophy following denervation has been tentatively ascribed to the influence of glucocorticoids (G) because of the rapid increase of cytosolic G receptors (RG) after sciatic nerve section. It appears however that the level of muscular atrophy is similar: 1. in slow or fast-twitch muscles in spite of huge variations in RG; 2. in intact or adrenalectomized (ADR-X) rats. Moreover, the protein muscle profile of intact or ADR-X rats after gel electrophoresis is similar but drastically decreased after 3 weeks of denervation. We conclude that there is no causeeffect relationship between muscle atrophy and RG elevation after nerve section.

We have established an assay to determine total cytoplasmic glucocorticoid receptor sites in heart, vastus and levator-ani-bulbocavernosus muscles from rats. We have tested the exchange of endogenously bound hormone with labeled triamcinolone acetonide by performing long incubation at 0-4 degrees C. This procedure appeared to produce an adequate exchange of exogenously added unlabeled corticosterone in the range of 16 nM (normal unstressed concentration of corticosterone in plasma) with vastus and levator ani-bulbocavernosus muscles. Beyond that level, the displacement of unlabeled corticosterone by labeled triamcinolone acetonide was less efficient. By contrast, in heart and especially in liver cytosols, the exchange was adequate even in the presence of high concentrations of corticosterone (64 and 460 nM respectively). Using the exchange assay conditions (20 h of incubation at 0-4 degrees C with 16 nM of labeled triamcinolone acetonide), we found no significant difference between glucocorticoid receptor levels in intact male and female rats. In both sexes, these glucocorticoid receptor values were not affected by gonadectomy, but increased more than 2-fold after adrenalectomy. No seasonal variations were recorded in intact or adrenalectomized rats.

When Sephadex G-25 columns are used to separate transcortin-bound corticosterone from free corticosterone, there is a non-linear increase of total binding with increasing plasma volume filtered. However, the specific binding (total binding — unspecific binding) shows a linear relationship with the plasma volume filtered. Furthermore, the specific binding decreases with increasing Sephadex column length and absolute binding values are found by extrapolating to a zero length column.

The androgen-dependent levator ani (LA) muscle of the rat provides a suitable model to explore the molecular mechanism of steroid hormone action in target tissues. The objective of the present series of experiments was to study the effect of gonadectomy (GDX) and androgen replacement therapy on the in vitro protein synthetic capacity of the LA muscle. The incorporation of labeled methionine into the contractile protein fraction of the LA muscle maintained in organ culture decreases in a time-dependent manner following GDX. Translation of total polyadenylated mRNA in the rabbit reticulocyte translation system revealed that the decrease in protein synthetic capacity was not associated with differences in the template activity of the mRNA derived from GDX tissue. However, when polyribosomes were used to direct the same in vitro synthesis system, a significant time-dependent loss of translational activity was observed following GDX. The polyribosomes of the LA muscle of control and GDX rats were shown to contain equivalent amount of rRNA and mRNA of comparable translation efficiency. Collectively the results of these experiments indicate that the decrease in protein synthetic capacity of the LA muscle in androgen deficient rats is due, in part, to a repression of the translation process associated to the functional integrity of polyribosomes.

High serum corticosterone levels and transient depletion of cytosolic glucocorticoid receptor binding capacity were observed in rat cardiac muscle following immobilization stress. To evaluate the effect of this treatment on the protein synthetic capacity, biologically active polyribosomes were used to direct the in vitro synthesis of polypeptides in the rabbit reticulocyte lysate. The results of these experiments indicate that the template activity of several messenger RNAs coding for major myofibrillar proteins was increased. This change in protein synthetic activity was not observed in adrenalectomized animals. Collectively, these results suggest that glucocorticoids are involved in the regulation of cardiac protein biosynthesis.