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Colorectal cancer detection in a Community Hospital Screening Program.

In its first 4 1/2 years of operation in the Long Beach Community Hospital Cancer Detection Center, among the 5,595 persons examined, 16 cases of colorectal cancer were discovered. Fourteen of the 16 had symptoms referable to neoplasms. Eight had lesions found on proctosigmoidoscopic examination. Nine had positive findings for occult blood in stool samples, a 7.5% cancer detection rate among the 120 with positive stool sample findings. Six patients with cancer submitted one to four stool specimens that showed negative findings on occult blood testing, and one patient submitted no specimen. Although valuable in screening, stool testing for occult blood will not detect all colonic neoplasms. The complaints of pain, altered bowel habits, or tenesmus warrant sigmoidoscopic examination, barium enema studies, or both, whether findings in stool samples are positive or negative.

Adult↗

POISE: Spectral Inference of Parent-of-Origin Effects in Unlabeled Genomic Data.

MOTIVATION: Parent of Origin Effects (POEs), where the effect of an an allele on a phenotype differs based on maternal or paternal inheritance implicated in growth, metabolism, and neurodevelopment. Traditional tests for POEs require family data to determine parental origins of transmitted alleles. Given that such studies are expensive and time consuming compared to genome-wide association studies (GWAS), tests that function absent inheritance information are highly desirable. We develop a method, based on community detection from machine learning, that infers POEs via a spectral decomposition, obtains confidence intervals via a non-parametric bootstrap, and safeguards against confounding by non POE sources of variation. We refer to our method as Parent of Origin Inference via Spectral Estimation (POISE). RESULTS: We demonstrate that POISE is well-calibrated under both Gaussian and heavy-tailed noise in simulation studies, with improved robustness to true POEs compared to existing covariance-based tests. POISE provides per-trait effect estimates with bias-corrected bootstrap confidence intervals and incorporates an information-theoretic minimum detectable effect size that filters unreliable estimates, conferring robustness to covariance-deflating variance QTL. We then apply POISE to GWAS data from the UK Biobank using BMI, LDL cholesterol, and HDL cholesterol. POISE recovers established POE loci and identifies 134 additional variants at genes implicated in lipid metabolism, immune regulation, and growth. AVAILABILITY AND IMPLEMENTATION: The code for this method in Python is available at https://github.com/bystrogenomics/POISE.

Community Detection↗

Microarrays for bacterial detection and microbial community analysis.

Several types of microarrays have recently been developed and evaluated for bacterial detection and microbial community analysis. These studies demonstrated that specific, sensitive and quantitative detection could be obtained with both functional gene arrays and community genome arrays. Although single-base mismatch can be differentiated with phylogenetic oligonucleotide arrays, reliable specific detection at the single-base level is still problematic. Microarray-based hybridization approaches are also useful for defining genome diversity and bacterial relatedness. However, more rigorous and systematic assessment and development are needed to realize the full potential of microarrays for microbial detection and community analysis.

Bacteria↗

IgG1 and IgG4 serum antibody responses in asymptomatic and clinically expressed cystic echinococcosis patients.

IgG1 and IgG4 subclass antibody responses were investigated in two clinically different groups of hepatic cystic echinococcosis (CE) patients. One group consisted of surgically proven CE cases (clinically expressed hospitalized cases) and a second group comprised asymptomatic CE patients (first time community detected cases) diagnosed by portable ultrasound and serology in four different endemic communities. Fifty eight sera from surgically proven CE patients and 133 sera from asymptomatic ultrasound diagnosed CE cases were screened by ELISA using purified human hydatid cyst fluid antigen B for total specific IgG, IgG1 and IgG4 antibodies. Fifty sera from healthy individuals from within endemic regions were used as control negatives. Compared to control negatives total IgG antibody levels were elevated in both surgically proven (85%) and asymptomatic CE cases (77%) but there was no significant difference between the two groups. IgG1 subclass antibody levels were also elevated in both surgically proven (55%) and asymptomatic cases (58%) compared to endemic controls and similarly the difference in this response was not significant between these two groups. In contrast the prevalence of IgG4 antibodies in surgically confirmed chronic CE patients was greater (71%) than the respective IgG1 antibody levels (55%). The greatest difference in specific antibody response, between advanced surgically confirmed CE patients and ultrasound detected asymptomatic CE cases, was observed for IgG4 antibody levels which were detected in 71% of symptomatic compared to only 23% of asymptomatic patients (P < 0.0001). These observations confirm that IgG4 is an important diagnostic parameter for clinically expressed cystic echinococcosis in humans and suggest that a switch from a predominant IgG1 response to IgG4 might occur in CE patients as the disease progresses.

Animals↗

Use of 16S rRNA-targeted oligonucleotide probes to investigate the distribution of sulphate-reducing bacteria in estuarine sediments.

The distribution of sulphate-reducing bacteria (SRBs) in three anaerobic sediments, one predominantly freshwater and low sulphate and two predominantly marine and high sulphate, on the River Tama, Tokyo, Japan, was investigated using 16S rRNA-targeted oligonucleotide probes. Hybridisation results and sulphate reduction measurements indicated that SRBs are a minor part of the bacterial population in the freshwater sediments. Only Desulfobulbus and Desulfobacterium were detected, representing 1.6% of the general bacterial probe signal. In contrast, the SRB community detected at the two marine-dominated sites was larger and more diverse, representing 10-11.4% of the bacterial signal and with Desulfobacter, Desulfovibrio, Desulfobulbus and Desulfobacterium detected. In contrast to previous reports our results suggest that Desulfovibrio may not always be the most abundant SRB in anaerobic sediments. Acetate-utilising Desulfobacter were the dominant SRB in the marine-dominated sediments, and Desulfobulbus and Desulfobacterium were active in low-sulphate sediments, where they may utilise electron acceptors other than sulphate.

Journal Article↗

Defining and identifying communities in networks.

The investigation of community structures in networks is an important issue in many domains and disciplines. This problem is relevant for social tasks (objective analysis of relationships on the web), biological inquiries (functional studies in metabolic and protein networks), or technological problems (optimization of large infrastructures). Several types of algorithms exist for revealing the community structure in networks, but a general and quantitative definition of community is not implemented in the algorithms, leading to an intrinsic difficulty in the interpretation of the results without any additional nontopological information. In this article we deal with this problem by showing how quantitative definitions of community are implemented in practice in the existing algorithms. In this way the algorithms for the identification of the community structure become fully self-contained. Furthermore, we propose a local algorithm to detect communities which outperforms the existing algorithms with respect to computational cost, keeping the same level of reliability. The algorithm is tested on artificial and real-world graphs. In particular, we show how the algorithm applies to a network of scientific collaborations, which, for its size, cannot be attacked with the usual methods. This type of local algorithm could open the way to applications to large-scale technological and biological systems.

Algorithms↗

SdiA of Salmonella enterica is a LuxR homolog that detects mixed microbial communities.

Proteins of the LuxR family detect the presence of N-acylhomoserine lactones (AHLs) and regulate transcription accordingly. When AHLs are synthesized by the same species that detects them, the system allows a bacterium to measure the population density of its own species, a phenomenon known as quorum sensing. The sdiA genes of Escherichia coli and Salmonella enterica serovar Typhimurium are predicted to encode LuxR homologs. However, these species do not appear to synthesize AHLs or any other molecule detected by SdiA. It has previously been demonstrated that overexpression of sdiA results in the activation of the ftsQAZ locus in E. coli and four other loci in Salmonella serovar Typhimurium. Here we report that transcriptional fusions to these five loci fall into two classes. The first class requires overexpression of sdiA for activation. The second class responds to sdiA expressed from its natural position in the chromosome if the appropriate AHLs are added to the culture. The only member of the second class is a series of Prck-luxCDABE fusions in Salmonella serovar Typhimurium. SdiA responds with highest sensitivity to AHLs that have a keto modification at the third carbon and an acyl chain length of 6 or 8 (half-maximal response between 1 and 5 nM). Growth of Salmonella in proximity to species known to synthesize these AHLs results in sdiA-dependent activation of the Prck-luxCDABE fusions. SdiA appears to be the first AHL receptor discovered that detects signals emanating exclusively from other species.

4-Butyrolactone↗

Kinetic analyses of Biolog community profiles to detect changes in inoculum density and species diversity of river bacterial communities.

The kinetics of response curves from Biolog community profiles for heterotrophic bacteria from a river in Nova Scotia, Canada have been analyzed to generate lag, slope, and asymptote parameters. The river water samples were treated with one of three supplements of Escherichia coli (in situ levels, 10(3) CFU/mL, or 10(6) CFU/mL) and one of five concentrations of chlorine (0, 1, 3, 5, or 7 ppm) to satisfy a full factorial design. The chlorine treatments decreased the inoculum density by up to 2 log values and decreased the species evenness. The E. coli supplements increased the inoculum density and decreased the species richness. Examination of the asymptotes did not reveal any significant effects owing to E. coli, but differences owing to the chlorine were detected. Analyses of the slopes showed a similar insignificance of the effects of E. coli and a lack of treatment effect owing to chlorine. The lag analyses also showed no significant E. coli effects, but showed a significant effect owing to chlorine. The discrepancy produced with the slope analysis (i.e., no chlorine effect) may represent an anomaly of the Biolog community approach. The use of lag phase was impaired because of the problem of infinite lags from wells that had no response, but a principle component analysis with a reduced set of substrates did suggest some influence of E. coli on the community profile. An examination of the substrates metabolized by the river water compared with pure E. coli revealed that the Biolog profiles of the river communities were not a simple summation of the component parts. In light of the lack of uniformity between these analyses, where the outcome depended on which parameter was used, caution is advised in interpreting Biolog community profiles on the basis of only one parameter.

Analysis of Variance↗

[Clinical predictors for the detection of community-acquired pneumonia in adults as a guide to ordering chest radiographs].

We sought to identify sensitive clinical predictors for the detection of community-acquired pneumonia in adults as a guide to the ordering of chest radiographs. The subjects were 79 outpatients with at least one clinical sign of fever, cough, sputum, chest pain, dyspnea and coarse crackle who underwent radiography of the chest to detect pneumonia. The relationship between these clinical signs and the presence of pneumonia was examined. Twenty-four patients (30.4%) had pneumonia. Twenty-two of these had 4 clinical signs: fever, cough, sputum and coarse crackle. Altogether, twenty-six of the 79 patients had these 4 clinical signs, and of them, 22 had pneumonia. Between the 4 clinical signs and the presence of pneumonia, the sensitivity was 91.7% and the specificity was 92.7%. On the basis of the above, as a diagnostic strategy, the ordering of chest radiographs to detect community-acquired pneumonia in adults was recommended when patients showed the 4 clinical signs of fever, cough, sputum and coarse crackle.

Adolescent↗

Finding community structure in very large networks.

The discovery and analysis of community structure in networks is a topic of considerable recent interest within the physics community, but most methods proposed so far are unsuitable for very large networks because of their computational cost. Here we present a hierarchical agglomeration algorithm for detecting community structure which is faster than many competing algorithms: its running time on a network with n vertices and m edges is O (md log n) where d is the depth of the dendrogram describing the community structure. Many real-world networks are sparse and hierarchical, with m approximately n and d approximately log n, in which case our algorithm runs in essentially linear time, O (n log(2) n). As an example of the application of this algorithm we use it to analyze a network of items for sale on the web site of a large on-line retailer, items in the network being linked if they are frequently purchased by the same buyer. The network has more than 400 000 vertices and 2 x 10(6) edges. We show that our algorithm can extract meaningful communities from this network, revealing large-scale patterns present in the purchasing habits of customers.

Journal Article↗

Glaucoma detection in the community: does ongoing training of optometrists have a lasting effect?

PURPOSE: To establish whether the effect of improved glaucoma detection in the community suggested by an intervention study is maintained when intervention is extended to include all optometrists in the area. METHODS: Optometrists' in the Ealing, Hammersmith, and Hounslow area were invited to ongoing training sessions following completion of an intervention study. The number of optometrist initiated referrals to Ealing Hospital Eye Clinic (EHEC) for suspect glaucoma was assessed over a 12-month period. The positive predictive value (PPV) of those referrals was calculated and a historical comparison made with the results of the original study. RESULTS: A total of 376 new referrals for suspected glaucoma were assessed at EHEC during the 12-month period of data collection. This represents an increase in the number of referrals of 58% compared with an equivalent 12-month period during the initial intervention trial (376 vs. 238). The PPV was maintained at 0.45 (95% CI 0.41-0.51). CONCLUSION: The rising number of new referrals for glaucoma together with maintenance of the PPV suggests an impact on the number of new cases of glaucoma detected in the community. The increase in referral numbers was limited to glaucoma when compared with new referrals for cataract. This implies a targeted effect of the intervention in terms of glaucoma detection. We believe the next step is to perform the study in an alternative location to see if the effect is repeatable elsewhere. If proven to be the case, there is a coherent argument for widespread adoption of this strategy to improve glaucoma case finding.

Community Health Services↗

Oncology nursing in the small community hospital.

Coordinating the nursing component of a community hospital's cancer program requires a clear definition of the facility's mission as it relates to cancer care and the scope of cancer nursing within the facility. Program managers need to assess the hospital's strengths and weaknesses, as well as local, regional, and national trends that impact on the hospital's ability to implement a cancer care program that is fiscally realistic and salient to its targeted population. The major advantages community hospitals have over large medical centers are convenience and ability to control the hospitalization experience. Nurses play a key role in creating a positive experience for patients and families in a variety of cancer care services, including prevention and early detection, community outreach and education, standard cancer therapy, ambulatory care, and other post-acute services.

Hospitals, Community↗

Survival of patients with colorectal cancer detected by a community screening program.

OBJECTIVE: To determine survival rates for people with colorectal cancer detected through Bowelscan, a community screening program. DESIGN: Survey of data from local medical practitioners, and comparison with data from State cancer registries. SUBJECTS AND SETTING: 249 people with colorectal cancer detected after faecal occult blood screening in north-eastern New South Wales, 1987-1996. Follow-up was in 1998-1999. MAIN OUTCOME MEASURES: Five-year survival rates and relative survival ratios. RESULTS: Five-year survival rates for the screen-detected cancer patients were 90% for those with Dukes' stage A cancers, 75% for Dukes' B, 52% for Dukes' C and 0 for Dukes' D (although one person with Dukes' D cancer was living at four-year follow-up at the end of the study). Because of the higher percentage of Dukes' A cases in the population whose cancer was detected through screening, the resulting five-year relative survival ratio was significantly better than for those recorded by New South Wales, South Australian and Queensland cancer registries: 0.82 (95% confidence interval, 0.74-0.90) compared to 0.59 (P < or = 0.001). CONCLUSIONS: The study supports the findings of three overseas randomised trials that screening reduces mortality from colorectal cancer. We estimate that screening 200,000 people would detect about 250 colorectal cancers and prevent as many as 55 deaths.

Adult↗

Screening for thyroid disease.

PURPOSE: To evaluate the usefulness of screening for thyroid dysfunction in various clinical settings. DESIGN: Review and synthesis of the literature. MAIN RESULTS: Screening in the community detects new overt thyrotoxicosis or hypothyroidism in approximately 0.5% of the general population. The yield is best among women over 40 years of age (1%) and is lowest among young men (0%). Case-finding (testing clinic patients who are seeing a physician for unrelated reasons) has a better yield and is less expensive than screening in the community. Patients hospitalized with acute illnesses do not benefit from routine thyroid function testing. However, patients who are admitted to specialized geriatric units because of general disability, failure to thrive, and other indications may benefit. In various studies, from 2% to 5% of patients admitted to geriatric units have treatable thyroid disease. The serum total thyroxine, free thyroxine index, free thyroxine, and sensitive thyrotropin assay are all effective as initial tests for screening. The sensitive thyrotropin assay is less cost-effective than the other choices. RECOMMENDATIONS: Case-finding in some women over 40 years of age can be useful. Patients admitted to specialized geriatric units may also benefit from routine testing. Thyroid function tests are not indicated for community screening programs or for patients hospitalized with acute medical or psychiatric illnesses.

Adult↗

Second trimester screening for Down's syndrome: 7 years experience.

OBJECTIVES: To evaluate the effectiveness of the first 7 years of a programme for second trimester antenatal screening for Down's syndrome, using alpha-fetoprotein (alphaFP) and total human chorionic gonadotropin (hCG) as maternal serum markers. METHODS: A clinical biochemistry laboratory providing a screening service for four obstetric units. Women attending for antenatal care who accepted an offer of serum screening for Down's syndrome were tested between 15 and 20 weeks gestation. Down's risk estimates were calculated using maternal serum alphaFP and total hCG results as modifiers of the maternal age related risk. Outcome was determined in collaboration with the regional cytogenetics unit. RESULTS: In 7 years 66,631 women were screened, in whom 108 Down's syndrome pregnancies were identified. Risks for Down's syndrome were reported without a specified cut off recommendation; however, at a cut off of 1 in 250, 72 (66.7%) of the affected pregnancies were screen positive, the false positive rate was 5.8%, and the uptake of amniocentesis 71.2%. The detection rate was higher in women screened before 17 weeks (70.5%) than in those screened at 17 weeks or later (56.7% overall and 20.0% in those under 30 years). The uptake of screening declined gradually from 84% in 1992 to 59.5% in 1998. CONCLUSIONS: Two marker screening using aFP and total hCG is an effective way of screening for Down's syndrome and is widely accepted in the local community. Detection rates were comparable with other second trimester studies using two markers including both total and free beta hCG.

Adult↗

Ordination of zooplankton community data to detect pesticide effects in pond enclosures

Trends in community structure of crustacean zooplankton among 17 forest pond enclosures (5 m x 5 m x 1 m deep) were examined and analyzed to determine effects of two candidate forest pesticides. Eight enclosures were treated at two concentrations of an experimental insecticide, tebufenozide; five were treated at two concentrations of a biological herbicide, bialaphos; and four served as controls. Zooplankton community structure was characterized by ordination of species assemblages using principle components analysis (PCA) and correspondence analysis (CA). Two-dimensional plots of the first two axes from PCA and CA were constructed to explore temporal and treatment-related patterns in community structure. The first four axes of both ordination functions were used as multivariate descriptors of community structure and were examined for differences among treatments by ANOVA. Species ordination plots and sorted rotated factor loadings provided objective means of identifying the species important in determining divergence in community structure. These were considered indicator species and were examined for differences among treatments by ANOVA and specified contrasts. The ordination and subsequent analysis revealed trends in community structure and sample differences that indicated clear, concentration-dependent effects of bialaphos and equivocal effects of tebufenozide.

Journal Article↗

Effects of an education program for community pharmacists on detecting drug-related problems in elderly patients.

Community pharmacists are in a position to assume increased responsibility for preventing and resolving drug-related problems in ambulatory patients. Such an expanded role is mandated under provisions of the Omnibus Budget Reconciliation Act of 1990. The need for pharmacist oversight of drug therapy may be most acute in elderly patients. This study reports on a program to teach community pharmacists a process of assessing drug therapy of elderly patients and intervening to correct problems. Community pharmacists (N = 102) were assigned to treatment and control conditions. Both groups targeted patients meeting criteria and enrolled them into the study. Treatment group pharmacists, who participated in a training program, also assessed the medication use of enrolled patients to identify and resolve medication-related problems. Patients (N = 762) were telephoned by researchers 1 month after enrollment for an interview. Comparisons between treatment and control group patients were made on reports of pharmacist activities, knowledge of regimens, compliance, and potential drug therapy problems, such as interactions and side effects. Treatment patients were more likely to report that pharmacists provided information and assessed for problems than were control patients. These differences were maintained on 3-month follow-up questionnaires. No differences were found on the odds that patients indicated misunderstanding of regimens, non-compliance, or potential therapeutic problems.

Aged↗

[Food-borne infections: do we need further data collection for public health action and research].

The data needed for controlling and preventing food-borne infectious diseases relied so far on surveillance of the main food-borne infections (Salmonella and listeria infections) to follow trends over time and detect outbreak. However, this systematic continuous data collection was not always sensitive enough to timely detect community outbreaks and did not take into account sporadic cases of food-borne infections which represent the majority of patients (such as Campylobacter infection for example). Therefore, the true burden of food-borne infections, including morbidity, mortality and the social and economic cost could not be assessed. As the issue of food-borne infections got more social attention, the need of further epidemiological data has increased including the implementation of large population studies (active surveillance and follow up studies) associated with analytical studies in the United States (Foodnet) and in some European countries (United Kingdom, The Netherlands, Denmark.). Meanwhile surveillance and detection of outbreaks have substantially improved through the use of new typing scheme, particularly those based on molecular techniques. Their routine use, now, allows an early identification of the clonal spread of food-borne bacteria. The application of automatic detection algorithm to surveillance data base has also improved the performance of outbreak detection and changes of trends. Furthermore, food-borne infection surveillance has become European which allows, by pooling of national database, to identify emergence that did not get noticed in any country. To foster the prevention of sporadic cases, the use of analytical epidemiology has become more and more frequent and has improved the knowledge of food vehicles and risk factors. The risk assessment approach has also been applied to the microbial contamination of food to answer to the increasing needs of expertise, particularly at the international level. This approach, however, needs further methodological development and the collection of extra information on the food chain. Last, but not the least, a wider public health research approach must also be considered, particularly on the social perception of food-borne risks and the cost-effectiveness analysis of the prevention measures that are taken.

Adult↗