Childhood food insecurity and incident diabetes: A longitudinal cohort study of 34 042 children in Ontario, Canada.

AIM: To examine the association between childhood food insecurity and incident diabetes. METHODS: Using health administrative databases linked to the Canadian Community Health Survey, we conducted a population-based cohort study of children aged <18 years from Ontario, Canada. Children without diabetes who had a household response to the Canadian Community Health Survey Household Food Security Survey Module were followed for a median of 9.5 years for incident diabetes. Multivariable Cox proportional hazards models were used to examine the association between childhood food insecurity and incident diabetes, adjusted sequentially for important clinical and socio-economic risk factors. RESULTS: We included 34 042 children, of whom 5.3% lived in food-insecure households. There were 184 new cases of diabetes, diagnosed at a median age of 16 and 18.5 years in food-secure and food-insecure children, respectively. In unadjusted analysis, childhood food insecurity was associated with an increased risk of incident diabetes (hazard ratio 1.69, 95% CI 1.01 to 2.81). When adjusted for clinical and socio-economic confounders, the relationship was no longer statistically significant (hazard ratio 1.55, 95% CI 0.91 to 2.66, adjusted for clinical confounders; hazard ratio 1.30, 95% CI 0.72 to 2.37, adjusted for clinical/socio-economic confounders). Our results remained robust in sensitivity analyses. CONCLUSIONS: Although food-insecure children are a medically and socially vulnerable population, they do not appear to be at increased risk of incident diabetes over a median of 9.5 years.

Age at migration and the risk of psychotic disorders: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of the existing evidence on the association between age at migration and the risk of psychotic disorders. METHODS: Observational studies were eligible for inclusion if they presented data on the association between age at migration and the risk of psychotic disorders among first-generation migrant groups. We used two random effects meta-analyses to pool effect estimates for each stratum of age at migration relative to (i) a native-born reference category and (ii) the youngest age stratum (0 to 2 years). RESULTS: Ten studies met inclusion criteria, and five were included in the meta-analysis. The risk of psychotic disorder among people who migrate prior to age 18 is nearly twice as high as the native-born population, with no evidence of effect modification by age strata. People who migrate during early adulthood (19 to 29 years) have a similar risk of psychotic disorder as the native-born population (IRR = 0.93, 95% CI = 0.60, 1.44) and a lower risk relative to those who migrate during infancy (0 to 2 years) (IRR = 0.58, 95% CI = 0.33, 1.04). CONCLUSIONS: Migrant status is one of few well-established risk factors for psychotic disorder, yet we have limited understanding of the underlying etiology. The findings of this review advance our understanding of this association and identify high-risk groups to target for intervention.

Concordance between health administrative data and survey-derived diagnoses for mood and anxiety disorders.

OBJECTIVE: To assess whether estimates of survey structured interview diagnoses of mood and anxiety disorders were concordant with diagnoses of these disorders obtained from health administrative data. METHODS: All Ontario respondents to the 2012 Canadian Community Health Survey-Mental Health (CCHS-MH) were linked to health administrative databases at ICES (formerly known as the Institute for Clinical Evaluative Sciences). Survey structured interview diagnoses were compared with health administrative data diagnoses obtained using a standardized algorithm. We used modified Poisson regression analyses to assess whether socio-demographic factors were associated with concordance between the two measures. RESULTS: Of the 4157 Ontarians included in our sample, 20.4% had either a structured interview diagnosis (13.9%) or health administrative diagnosis (10.4%) of a mood or anxiety disorder. There was high discordance between measures, with only 19.4% agreement. Migrant status, age, employment, and income were associated with discordance between measures. CONCLUSIONS: Our findings indicate that previous estimates of the 12-month prevalence of mood and anxiety disorders in Ontario may be underestimating the true prevalence, and that population-based surveys and health administrative data may be capturing different groups of people. Understanding the limitations of data commonly used in epidemiologic studies is a key foundation for improving population-based estimates of mental disorders.

Improvements in the method of radiation anomaly detection by spectral comparison ratios.

We present a new procedure for configuring the Nuisance-rejection Spectral Comparison Ratio Anomaly Detection (N-SCRAD) method. The procedure minimizes detectable count rates of source spectra at a specified false positive rate using simulated annealing. We also present a new method for correcting the estimates of background variability used in N-SCRAD to current conditions of the total count rate. The correction lowers detection thresholds for a specified false positive rate, enabling greater sensitivity to targets.

A meta-analysis of ethnic differences in pathways to care at the first episode of psychosis.

OBJECTIVE: We sought to systematically review the literature on ethnic differences in the likelihood of general practitioner (GP) involvement, police involvement, and involuntary admission on the pathway to care of patients with first-episode psychosis (FEP). METHOD: We searched electronic databases and conducted forward and backward tracking to identify relevant studies. We calculated pooled odds ratios (OR) to examine the variation between aggregated ethnic groups in the indicators of the pathway to care. RESULTS: We identified seven studies from Canada and England that looked at ethnic differences in GP involvement (n=7), police involvement (n=7), or involuntary admission (n=5). Aggregated ethnic groups were most often compared. The pooled ORs suggest that Black patients have a decreased likelihood of GP involvement (OR=0.70, 0.57-0.86) and an increased likelihood of police involvement (OR=2.11, 1.67-2.66), relative to White patients. The pooled ORs were not statistically significant for patients with Asian backgrounds (GP involvement OR=1.23, 0.87-1.75; police involvement OR=0.86, 0.57-1.30). There is also evidence to suggest that there may be ethnic differences in the likelihood of involuntary admission; however, effect modification by several sociodemographic factors precluded a pooling of these data. CONCLUSION: Ethnic differences in pathways to care are present at the first episode of psychosis.

Spinal emergencies.

True spinal emergencies are rare and represent a potential loss of function if not treated properly. This review describes the most frequently encountered spinal emergencies. Early diagnosis is the key to preventing significant morbidity in the form of permanent disability. The recognition of red flags, followed by a thorough neurologic exam and appropriate imaging, should prompt a thorough examination with a heightened sense of urgency regarding the workup for serious forms of pathology. Spinal emergencies threaten loss of function if not treated properly. Providers must be aware of the presenting symptoms and be able to accurately interpret imaging results in order to promptly diagnose and treat these conditions.

Calosphaeria Canker of Sweet Cherry Caused by Calosphaeria pulchella in California and South Australia.

California is the second largest sweet cherry producer in the United States with annual revenues up to $200 million. The South Australian cherry industry generates about 10% of Australia's overall production with approximately 1,500 metric tons of cherries produced yearly. In California, perennial canker diseases and subsequent branch dieback are responsible for extensive damage throughout sweet cherry orchards, reducing annual yields and tree longevity. Surveys of cherry orchards and isolation work were conducted in California to identify the main canker-causing agents. Calosphaeria pulchella was the main fungus isolated from cankers, followed by Eutypa lata and Leucostoma persoonii, respectively. Preliminary surveys in cherry orchards in South Australia documented C. pulchella and L. persoonii in cankers. The pathogenicity of C. pulchella in sweet cherry was confirmed following field inoculations of 2- to 3-year-old branches. C. pulchella was able to infect healthy wood and produce cankers with as much virulence as E. lata or L. persoonii. Spore trapping studies were conducted in two sweet cherry orchards in California to investigate the seasonal abundance of C. pulchella spores. Experiments showed that rain and sprinkler irrigation were important factors for aerial dissemination. Finally, this study illustrates the symptoms and signs of the new disease Calosphaeria canker.

The pathways to mental health care of first-episode psychosis patients: a systematic review.

BACKGROUND: Although there is agreement on the association between delay in treatment of psychosis and outcome, less is known regarding the pathways to care of patients suffering from a first psychotic episode. Pathways are complex, involve a diverse range of contacts, and are likely to influence delay in treatment. We conducted a systematic review on the nature and determinants of the pathway to care of patients experiencing a first psychotic episode.MethodWe searched four databases (Medline, HealthStar, EMBASE, PsycINFO) to identify articles published between 1985 and 2009. We manually searched reference lists and relevant journals and used forward citation searching to identify additional articles. Studies were included if they used an observational design to assess the pathways to care of patients with first-episode psychosis (FEP). RESULTS: Included studies (n=30) explored the first contact in the pathway and/or the referral source that led to treatment. In 13 of 21 studies, the first contact for the largest proportion of patients was a physician. However, in nine of 22 studies, the referral source for the greatest proportion of patients was emergency services. We did not find consistent results across the studies that explored the sex, socio-economic, and/or ethnic determinants of the pathway, or the impact of the pathway to care on treatment delay. CONCLUSIONS: Additional research is needed to understand the help-seeking behavior of patients experiencing a first-episode of psychosis, service response to such contacts, and the determinants of the pathways to mental health care, to inform the provision of mental health services.

First Report of Calosphaeria pulchella Associated with Branch Dieback of Sweet Cherry Trees in California.

California is the second largest sweet cherry producer in the United States with approximately 10,800 ha and an average annual crop value of approximately $150 million. Perennial canker diseases constitute major threats to the cherry industry productivity by reducing tree health, longevity, and yields. During the course of summer 2006, we observed severe limb and branch dieback of sweet cherry (Prunus avium L.) in San Joaquin, San Benito, Contra Costa, and Stanislaus counties of California. Isolation from diseased branches repeatedly yielded the fungus Calosphaeria pulchella (Pers.: Fr.) J. Schröt. (1,2). Cankers and vascular necroses had developed in tree limbs and branches, generally initiating from the heart wood and later spreading into the sapwood. External symptoms of disease may be unapparent throughout the early stages of infection, particularly in large diameter shoots. Older infections often appeared as wilted leaves. Branches and trunks affected with cankers from which C. pulchella was isolated also generally bore perithecia of C. pulchella beneath the periderm. Perithecia were nonstromatic and arranged in dense, circinate groups, with elongated necks converging radially and fissuring the periderm. Asci were unitunicate, clavate, and 45 to 55 × 5 to 5.5 µm. Ascospores were allantoid to suballantoid, hyaline, and 5 to 6 × 1 µm. Colonies on potato dextrose agar (PDA) were dark pink to red in their center with a white margin. Conidia were hyaline, allantoid to oblong-ellipsoidal, and (3-) 4 to 6 (-9) × 1.5 to 2 (-2.5) µm. Identification of C. pulchella isolates also was confirmed by sequence comparison in GenBank database using the internal transcribed spacer region (ITS1-5.8S-ITS2) of the rDNA. Sequences of California isolates shared 100% similarity with C. pulchella reference isolate CBS 115999 (EU367451) (2). ITS sequences of the California isolates used in this study were deposited into GenBank (Nos. HM237297 to HM237300). Pathogenicity of four isolates recovered from the margin of active cankers was determined by branch inoculations. In December 2006, 2- to 4-year-old twigs of P. avium cv. Bing were inoculated with a 5-mm cork borer to remove bark and by placing an agar plug from the growing margin of 8-day-old colonies directly into the fresh wound, mycelium side down. Ten branches per isolate were inoculated. Ten control shoots were inoculated with noncolonized agar plugs. Inoculations were covered with vaseline and wrapped with Parafilm to retain moisture. Branches were harvested in July 2007 and taken to the laboratory to be examined for canker development, and the extent of vascular discoloration in each branch was assessed. Isolations from the edge of discolored tissue were conducted to fulfill Koch's postulates. After 8 months, C. pulchella was reisolated from 100% of the inoculated branches. Length of vascular discoloration averaged 62.5 mm in branches inoculated with the four C. pulchella isolates and 16.5 mm in the control twigs. No fungi were reisolated from the slightly discolored tissue of the controls. To our knowledge, this study constitutes the first report of C. pulchella as a pathogen of sweet cherry trees in California. References: (1) M. E. Barr. Mycologia 77:549, 1985. (2) U. Damm et al. Persoonia 20:39, 2008.

Mixed-effects statistical model for comparative LC-MS proteomics studies.

Comparing a protein's concentrations across two or more treatments is the focus of many proteomics studies. A frequent source of measurements for these comparisons is a mass spectrometry (MS) analysis of a protein's peptide ions separated by liquid chromatography (LC) following its enzymatic digestion. Alas, LC-MS identification and quantification of equimolar peptides can vary significantly due to their unequal digestion, separation, and ionization. This unequal measurability of peptides, the largest source of LC-MS nuisance variation, stymies confident comparison of a protein's concentration across treatments. Our objective is to introduce a mixed-effects statistical model for comparative LC-MS proteomics studies. We describe LC-MS peptide abundance with a linear model featuring pivotal terms that account for unequal peptide LC-MS measurability. We advance fitting this model to an often incomplete LC-MS data set with REstricted Maximum Likelihood (REML) estimation, producing estimates of model goodness-of-fit, treatment effects, standard errors, confidence intervals, and protein relative concentrations. We illustrate the model with an experiment featuring a known dilution series of a filamentous ascomycete fungus Trichoderma reesei protein mixture. For 781 of the 1546 T. reesei proteins with sufficient data coverage, the fitted mixed-effects models capably described the LC-MS measurements. The LC-MS measurability terms effectively accounted for this major source of uncertainty. Ninety percent of the relative concentration estimates were within 0.5-fold of the true relative concentrations. Akin to the common ratio method, this model also produced biased estimates, albeit less biased. Bias decreased significantly, both absolutely and relative to the ratio method, as the number of observed peptides per protein increased. Mixed-effects statistical modeling offers a flexible, well-established methodology for comparative proteomics studies integrating common experimental designs with LC-MS sample processing plans. It favorably accounts for the unequal LC-MS measurability of peptides and produces informative quantitative comparisons of a protein's concentration across treatments with objective measures of uncertainties.

The need for additional safeguards in the informed consent process in schizophrenia research.

The process of obtaining informed consent to participate in a clinical study presents many challenges for research conducted in a population of patients with schizophrenia. Morally valid, informed consent must include information sharing, decisional capacity, and capacity for voluntarism. This paper examines the unique features of schizophrenia that may threaten each of these elements of informed consent, and it proposes additional safeguards in the process of gaining informed consent from individuals with schizophrenia in order to maximise the decision-making potential of this patient population.

Affinity purification of DNA and RNA from environmental samples with peptide nucleic acid clamps.

Bispeptide nucleic acids (bis-PNAs; PNA clamps), PNA oligomers, and DNA oligonucleotides were evaluated as affinity purification reagents for subfemtomolar 16S ribosomal DNA (rDNA) and rRNA targets in soil, sediment, and industrial air filter nucleic acid extracts. Under low-salt hybridization conditions (10 mM NaPO(4), 5 mM disodium EDTA, and 0.025% sodium dodecyl sulfate [SDS]) a PNA clamp recovered significantly more target DNA than either PNA or DNA oligomers. The efficacy of PNA clamps and oligomers was generally enhanced in the presence of excess nontarget DNA and in a low-salt extraction-hybridization buffer. Under high-salt conditions (200 mM NaPO(4), 100 mM disodium EDTA, and 0.5% SDS), however, capture efficiencies with the DNA oligomer were significantly greater than with the PNA clamp and PNA oligomer. Recovery and detection efficiencies for target DNA concentrations of > or =100 pg were generally >20% but depended upon the specific probe, solution background, and salt condition. The DNA probe had a lower absolute detection limit of 100 fg of target (830 zM [1 zM = 10(-21) M]) in high-salt buffer. In the absence of exogenous DNA (e.g., soil background), neither the bis-PNA nor the PNA oligomer achieved the same absolute detection limit even under a more favorable low-salt hybridization condition. In the presence of a soil background, however, both PNA probes provided more sensitive absolute purification and detection (830 zM) than the DNA oligomer. In varied environmental samples, the rank order for capture probe performance in high-salt buffer was DNA > PNA > clamp. Recovery of 16S rRNA from environmental samples mirrored quantitative results for DNA target recovery, with the DNA oligomer generating more positive results than either the bis-PNA or PNA oligomer, but PNA probes provided a greater incidence of detection from environmental samples that also contained a higher concentration of nontarget DNA and RNA. Significant interactions between probe type and environmental sample indicate that the most efficacious capture system depends upon the particular sample type (and background nucleic acid concentration), target (DNA or RNA), and detection objective.

Affinity capture and recovery of DNA at femtomolar concentrations with peptide nucleic acid probes.

The efficacy of PNA vs DNA oligomers for the recovery of femtomolar concentrations of 16S rDNA targets was determined with solution- and mixed-phase hybridization formats and limiting dilution quantitative PCR. Several results contradict existing perceptions of expected PNA behavior deduced from hybridization studies with oligonucleotide targets at high concentration. For example, DNA probes in the solution hybridization format performed as well as or better than PNA probes under high- or low-salt conditions, regardless of hybridization time or target size. In the mixed-phase hybridization format, however, PNA probes showed certain advantages, with more rapid and efficient binding/recovery of target nucleic acids regardless of target size. Recovery of target DNA with PNA probes was always more efficient in low-salt (20 mM in Na(+)) than high-salt (400 mM in Na(+-)) phosphate buffer. Recovery of target DNA by PNA probes was enhanced in the presence of excess, nontarget DNA, and differences in PNA efficacy under low- or high-salt conditions vanquished. In contrast, DNA probe performance was unaffected by the presence or absence of exogenous DNA in both solution- and mixed-phase hybridization formats. The absolute recovery and detection limit of the affinity purification method with either DNA or PNA probes was approximately 10(2) input target molecules at zeptamolar concentrations.

Measurement of pulpal blood flow in humans using laser Doppler flowmetry: a technique allowing stability and repeatability of pulpal blood flow measurement during surgical manipulations.

This study was undertaken to validate the repeatability of pulpal blood flow in human teeth with the laser Doppler flowmetry technique using a repeatable method of attachment of the laser Doppler probe. The variation in laser Doppler flowmetry measurements was evaluated over time periods that ranged from hours to days. In a prospective study, the pulpal blood flow was recorded from a maxillary central incisor (randomly selected) at a site directly gingival to the orthodontic bracket of three subjects. Measurements were made eight times over a 2-week period and every 30 minutes over 4 hours for eight recordings. The results indicated that there was only a slight difference between the temporal variability of the laser Doppler measurements over the course of 4 hours (intraday variability) or 2 weeks (interday variability). Furthermore, it appeared that subjects varied in their mean value recordings and may have varied widely in their respective signal-to-noise ratios.

Spontaneous orbital hemorrhage during general anesthesia and arthroplasty.

A 72-year-old woman who had a history of arthritis and cerebral vascular accident 4 years earlier underwent hand surgery. Because regional anesthesia was not successful, general anesthesia was administered. Shortly before extubation, proptosis developed in her left eye, and she was unable to open it. The condition was due to spontaneous orbital hemorrhage and resolved with conservative treatment.

Cerulein induces hyperplasia of the pancreas in a rat model of chronic pancreatic insufficiency.

Chronic pancreatic insufficiency (CPI) was induced in male Wistar rats by the injection of a zein-oleic acid-linoleic acid solution into their pancreaticobiliary ducts. Animals injected developed severe pancreatic atrophy with fibrosis and greater than 90% loss of pancreatic enzyme content. The animals also developed malabsorption of fat and bentiromide. Three weeks after the CPI lesion was induced, animals were randomized to receive cerulein 2 micrograms/kg twice daily subcutaneously or saline twice daily subcutaneously for 2 weeks. Cerulein significantly increased pancreatic trypsinogen (p less than 0.03), amylase (p less than 0.01), lipase (p less than 0.02), DNA (p less than 0.02), and RNA (p less than 0.01) content and improved fat and bentiromide malabsorption as compared to saline (p less than 0.05). We conclude that cerulein therapy can cause significant hyperplasia of pancreatic acinar parenchyma in an animal model of CPI and that this therapy can partially reverse malabsorption.

Comparison of the sensitivity and specificity of the CA19-9 and carcinoembryonic antigen assays in detecting cancer of the pancreas.

In this study, we determined the sensitivity and specificity of the new serum assay CA19-9 in detecting adenocarcinoma of the pancreas and compared the results with those of the serum assay to carcinoembryonic antigen (CEA). Thirty-seven patients with biopsy-proven adenocarcinoma (14 patients with resectable disease and 23 patients with unresectable disease) were compared with 157 controls (48 patients with benign pancreatic disease, 34 patients with nonpancreatic sources of abdominal pain, 58 patients with benign jaundice, 7 patients with nonpancreatic malabsorption, and 10 patients with renal failure on dialysis). It was determined that a cutoff of 75 U/ml enhanced the diagnostic efficiency (sensitivity + specificity) of CA19-9 over the manufacturer's recommended cutoff of 37 U/ml. The sensitivity of CA19-9 (greater than 75 U/ml) in detecting cancer was greater than that of CEA (greater than 5 ng/ml) (86.5% vs. 48.4%) (p less than 0.01, McNemar test). The sensitivity of CA19-9 was 78.6% in resectable and 91.3% in unresectable disease. The specificity of CA19-9 was also greater than CEA (92.5% vs. 87.3%), although this difference was not statistically significant. The higher the CA19-9 or CEA level, the greater the specificity of either assay; at CA19-9 levels greater than 600 U/ml and CEA levels greater than 20 ng/ml the specificity is approximately 99%. The combination of an elevated CA19-9 level (greater than 75 U/ml) and an elevated CEA level (greater than 5 ng/ml) also enhanced specificity to 99%. It is concluded that CA19-9 used alone is superior to CEA used alone in detecting cancer of the pancreas and that the combination of mild elevations of both assays improves their specificity. Although the CA19-9 marker can be elevated with other intraabdominal adenocarcinomas (e.g., gastric, biliary, or colonic), CA19-9, together with CEA, will be useful to the clinician in differentiating benign from malignant pancreatic processes and in alerting the clinician to the possible presence of an intraabdominal neoplasm in the proper clinical setting.

Predictive value of a low serum trypsinogen.

Previous studies, in selected populations, have determined that a low serum trypsinogen can be seen in chronic exocrine pancreatic disorders (CP) and primary diabetes mellitus (DM). In this study, we investigated the predictive value of a low serum trypsinogen. The study population consisted of 488 consecutive emergency room patients admitted to our hospital on whom a serum amylase was drawn by the emergency room staff. Of the sera drawn, 418 were saved and tested for immunoassayable trypsinogen. Ten of 418 (2.4%), had a low level of this marker (less than 10 ng/ml). Of these 10, four had obvious historical or clinical evidence of CP during their initial hospitalization. Six patients, however, had no initial evidence of CP. Follow-up was obtained in three of the six, and all three had evidence of CP despite absence of symptoms. Of the 418 patients, 37 had DM. A low trypsinogen was found in three of these 37, and all three had concomitant CP. We conclude that this new assay has excellent predictive value in diagnosing chronic exocrine pancreatic disorders.

Serum trypsinogen in diagnosis of chronic pancreatitis.

A new radioimmunoassay to serum trypsinogen (Cis Trypsik) was tested in several patient populations. A low serum trypsinogen level (less than 10 ng/ml) was found in 69.2% of 13 patients with chronic pancreatic insufficiency (CPI), in 100% of 10 patients with 95-100% pancreatectomy but only in 14% of 14 patients with cancer of the pancreas. A low trypsinogen level was not found in any of 68 control subjects or 10 patients with nonpancreatic steatorrhea. Nine patients with CPI or 95% pancreatectomy were retested a mean of six months after initial testing. Four of these nine (44.4%) had a significant variation in serum trypsinogen which would have led to a different diagnostic interpretation (two went from low to normal levels and two from normal to low levels). A mixed meal had little effect on serum trypsinogen levels in five of six patients with CPI, and pancreatic enzyme replacement therapy had no consistent effect on the serum trypsinogen level in seven patients with CPI or 95% pancreatectomy. It is speculated that minor subclinical episodes of focal pancreatitis may effect the serum trypsinogen level. Although there can be considerable variability using this assay, it still offers important clinical utility. A low trypsinogen level points to a chronic pancreatic process with excellent specificity. A normal trypsinogen level is of no help and should be repeated if clinical suspicion of chronic pancreatitis remains high.