Prospective Screen Research Articles

Predicting Nonresponse Bias from Teacher Ratings of Mental Health Problems in Primary School Children

The impact of nonresponse on estimates of mental health problems was examined in a prospective teacher screen in a community survey of 9,155 7-9 year olds. For 6,611 of the children, parents consented to participation in the actual study (Responders), while for 2,544 children parental consent was not obtained (Nonresponders). The teacher screen involved assessment of a broad set of symptoms of mental health problems and functional impairment. Calculations of non-response coefficients, a function of effect sizes and non-response proportion, revealed only ignorable nonresponse bias for both mean scores and correlations. However, the results from binary logistic regressions revealed that children ascribed signs of mental health problems by their teachers were less likely to participate. This was most frequent among children with only moderate symptoms. However, it also involved children with high symptom scores related to inattention, hyperactivity, emotions and peer relationship problems. These findings suggest that measures based on effect size can underestimate the magnitude of non-response bias and that a logistic regression approach may be more appropriate for studies geared at estimating prevalence of mental health problems in children.

Molecular cytogenetic characterization of TCF3 (E2A)/19p13.3 rearrangements in B‐cell precursor acute lymphoblastic leukemia

The t(1;19)(q23;p13.3) is one of the most common chromosomal abnormalities in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) and usually gives rise to the TCF3-PBX1 fusion gene. Additional rare, and sometimes cytogenetically cryptic, translocations involving the TCF3 gene have also been described. Using a dual color split-signal fluorescence in situ hybridization (FISH) probe, we have investigated the involvement of this gene in a series of BCP-ALLs harboring 19p13 translocations, as well as an unselected patient cohort. The TCF3 gene was shown to be involved in the majority of cases with a cytogenetically visible t(1;19) translocation, while the remaining TCF3-negative ALLs demonstrated breakpoint heterogeneity. Although most "other" 19p13 translocations did not produce a split-signal FISH pattern, a novel t(13;19)(q14;p13) involving TCF3 was discovered. A prospective screen of 161 children with BCP-ALL revealed a cryptic t(12;19)(p13;p13), another novel TCF3 rearrangement, and a series of patients with submicroscopic deletions of TCF3. These results demonstrate the utility of a split-signal FISH strategy in confirming the involvement of the TCF3 gene in 19p13 rearrangements and in identifying novel and cryptic TCF3 translocations. In addition to its role as a fusion partner gene, we propose that TCF3 can also act as a tumor suppressor gene in BCP-ALL.

Human MutL homolog (MLH1) function in DNA mismatch repair: a prospective screen for missense mutations in the ATPase domain.

Germline mutations in the DNA mismatch repair (MMR) genes MSH2 and MLH1 are responsible for the majority of hereditary non-polyposis colorectal cancer (HNPCC), an autosomal-dominant early-onset cancer syndrome. Genetic testing of both MSH2 and MLH1 from individuals suspected of HNPCC has revealed a considerable number of missense codons, which are difficult to classify as either pathogenic mutations or silent polymorphisms. To identify novel MLH1 missense codons that impair MMR activity, a prospective genetic screen in the yeast Saccharomyces cerevisiae was developed. The screen utilized hybrid human-yeast MLH1 genes that encode proteins having regions of the yeast ATPase domain replaced by homologous regions from the human protein. These hybrid MLH1 proteins are functional in MMR in vivo in yeast. Mutagenized MLH1 fragments of the human coding region were synthesized by error-prone PCR and cloned directly in yeast by in vivo gap repair. The resulting yeast colonies, which constitute a library of hybrid MLH1 gene variants, were initially screened by semi-quantitative in vivo MMR assays. The hybrid MLH1 genes were recovered from yeast clones that exhibited a MMR defect and sequenced to identify alterations in the mutagenized region. This investigation identified 117 missense codons that conferred a 2-fold or greater decreased efficiency of MMR in subsequent quantitative MMR assays. Notably, 10 of the identified missense codons were equivalent to codon changes previously observed in the human population and implicated in HNPCC. To investigate the effect of all possible codon alterations at single residues, a comprehensive mutational analysis of human MLH1 codons 43 (lysine-43) and 44 (serine-44) was performed. Several amino acid replacements at each residue were silent, but the majority of substitutions at lysine-43 (14/19) and serine-44 (18/19) reduced the efficiency of MMR. The assembled data identifies amino acid substitutions that disrupt MLH1 structure and/or function, and should assist the interpretation of MLH1 genetic tests.

Photostimulated process in CsBrCl:Eu2+: a promising image screen phosphor

CsBrCl and CsBrCl:Eu2+ have been grown by “Double Run Bridgman technique”. Optical investigations have been carried out on the samples. The formation of F(Br−) and F(Cl−) centers have been confirmed by optical absorption bands at 640 and 615nm, respectively. The photoluminescence (PL) spectra for europium (100ppm) doped CsBrCl samples give emission of europium at 442nm. This 442nm emission is due to the transition from T2g component of 4f65d configuration to the ground state 8S of europium. The emission due to the presence of impurities in the host lattice is detected by PL technique. The OH− impurity in the host lattice due to decomposition of the salt in open air gives out emission at 395 and 365nm. The O2− emission is observed at 465 and 468nm. Photostimulated luminescence (PSL) process is studied in the samples by exciting them at F-absorption wavelength after irradiation. No PSL is observed for the undoped CsBrCl samples grown in vacuum. The PSL of vacuum grown CsBrCl:Eu2+ samples for excitations at 640nm [F(Br−)] and 615nm [F(Cl−)] is observed at 420nm. It is deciphered that both F(Cl−) and F(Br−) centers contribute to PSL. The two F-centers noticed in absorption are stimulated separately; the resulting PSL signal confirms the participation of F-centers in photostimulated process. The lifetime of the PSL emission for CsBrCl:Eu2+ is determined to be 0.69μs. Application of the material as a prospective image screen phosphor is elaborated based on PSL results.

Hypoalbuminemia as a Cause of Pleural Effusions

Alterations in Starling forces that favor pleural fluid formation include an elevation in capillary hydrostatic pressure and a fall in plasma oncotic pressure. Although venous hypertension is a well-recognized cause of pleural effusion, the frequency with which hypoalbuminemia in the absence of volume expansion leads to pleural effusion is unclear. We determined the frequency with which unexplained pleural effusions occur in patients with normal and low plasma oncotic pressures. A 2-month prospective screen of all admission patients to the University of Oklahoma Hospital and the Oklahoma City Veterans Administration (VA) Medical Center identified 152 patients who had chest radiographs and serum protein determinations on admission, but did not have an admission diagnosis that was a recognized cause of pleural effusion. In order to include more patients in the study with extremely low serum albumin levels, 20 additional study patients with serum albumin levels of < 2.0 g/dL were identified by a retrospective review of patients admitted during the previous 12 months. On the radiograph, pleural effusions were identified as a new blunting of the costophrenic angles. Study patients were divided into the following three groups: group 1 had serum albumin levels of > 3.5 g/dL; group 2 had serum albumin levels between 2.1 and 3.5 g/dL; and group 3 had serum albumin levels of < or = 2.0 g/dL. Finally, the frequencies with which pleural effusions occurred were compared among the three groups. Seven of 104 patients in group 1, 2 of 45 patients in group 2, and 3 of 21 patients in group 3 had pleural effusions. Within each group, there were no significant differences in serum albumin concentration or plasma oncotic pressure between patients with and without pleural effusions. In all but two study patients, a careful review of records and a prospective follow-up of the patients' clinical course identified a potential cause for the effusions other than hypoalbuminemia. None of the 68 study patients with serum albumin levels of < or = 3.5 g/dL had an unexplained pleural effusion. We conclude that hypoalbuminemia, per se, is an uncommon cause of pleural effusion. The recognition of pleural effusions in patients with low serum albumin levels should prompt careful clinical evaluations to identify other potential causes for the effusions.

The incidence and causes of hypercalcaemia.

A prospective screen for hypercalcaemia in 58,053 hospital in-patients was conducted over 12 months. The incidence of hypercalcaemia was 0.6%, being transient in 19.2% of patients and sustained in the remainder. The most common causes in the sustained group were malignancy (45%) and primary hyperparathyroidism (16.5%). The incidence of primary hyperparathyroidism was 78/100,000 hospital in-patients, and its discovery was directly attributable to the survey in over half the cases.

Effect of specific antisera on the redistribution of chlorinated biphenyls in the mouse

Antisera prepared in rabbits against 4-Monochlorobiphenyl and 3,4,3′,4′-Tetrachlorobiphenyl were used to alter the tissue distribution of these environmental pollutants in the mouse. Mice were passively immunized with rabbit antisera following the absorption and distribution of the substituted biphenyls. Immunization caused in vivo redistribution of the compounds into the vascular space. Tissue/blood concentration ratios were greater in the control than in the antiserum treated animals. Changes intissue/blood ratios were similar to the serum/ antiserum ratios as determined by equilibrium dialysis experiments. These results indicate that it is possible to remove chlorinated biphenyls from tissue stores using specific antisera. Second, the partition of compounds between control serum and specific antiserum may be useful as a prospective screen to detect antisera with sufficient antigen affinity for tissue redistribution studies.