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Chromosome 22q11.2 deletion syndrome (22q11DS) is characterised by a complex behavioural phenotype including anxiety, attention-deficit/hyperactivity disorder and psychosis. In the current study, we aimed at improving our understanding of the heterogeneity of behavioural characteristics in a group of 129 young people (aged 4022) with a confirmed 22q11.2 microdeletion and 116 age and gender matched typically developing controls. Half the participants with 22q11DS had behaviour characterised by emotion dysregulation. A cluster analyses, of the participants with 22q11DS, revealed four groups characterised by intact emotion regulation; predominantly internalizing problems; both internalizing and externalizing problems; and predominantly externalizing difficulties. Importantly, it was found that young people with 22q11DS whose emotion dysregulation was characterised by externalizing problems had the poorest levels of functioning. As our understanding of 22q11DS improves, it is becoming increasingly clear that we need a better understanding of how individual differences and psychosocial factors contribute to, and interact with one another, to result in the observable individual differences in the 22q11DS behavioural phenotype.

Background/aims To evaluate treatment with custom, three-dimensional (3D) printed conformers for socket expansion in congenital microphthalmia and anophthalmia (MICA). Methods Retrospective analysis of prospective cohort from 2016 to 2020. All children received custom-made 3D-printed conformers increasing in size. We measured height, width, thickness, surface and volume of first and consecutive conformers, as well as horizontal palpebral fissure length (HPF) at start and follow-up visits. We analysed these parameters for severely (<45%) and moderately (>45%-75%) affected children, based on affected axial length on ultrasonography. Results We included 18 cases (9 severe, 9 moderate) with a total of 174 conformers (88 severe, 86 moderate) and a mean follow-up of 2.8 years (range 1.3-4.8). The mean relative HPF increased from 77% to 93% with 16/17 cases reaching >80%, and 12/17 cases >90% symmetry. Horizontal and vertical conformer dimensions increased up to 10 months of treatment, with a steeper slope for the severe group (10.5% vs 5.5% for height and 9.0% vs 6.1% for width gain per treatment month, for severe and moderate MICA, respectively). After 10 months of treatment conformer height and width increased only slightly. No serious complications were observed. Conclusion 3D-design and printing of solid conformers results in highly acceptable horizontal eyelid symmetry in the treatment of congenital MICA. The mean increase in conformer height and width in the first 10 months should be about 170% for moderate and about 200% for severe MICA. The presented conformer size formulas can aid ophthalmologists and ocularists to plan conformer treatment. [ABSTRACT FROM AUTHOR]

Children with one of two genetic disorders (chromosome 22q11.2 deletion syndrome and Turner syndrome) as well typically developing controls, participated in three cognitive processing experiments. Two experiments were designed to test cognitive processes involved in basic aspects numerical cognition. The third was a test of simple manual motor reaction time. Despite significant differences in global intellectual abilities, as measured by IQ tests, performance on the two numerical cognition tasks differed little between the two groups of children with genetic disorders. However, both performed significantly more poorly than did controls. The pattern of results are consistent with the hypothesis that impairments were not due to global intellectual ability but arose in specific cognitive functions required by different conditions within the tasks. The fact that no group differences were found in the reaction time task, despite significant differences in the standardized processing speed measure, further supports the interpretation that specific cognitive processing impairments and not global intellectual or processing speed impairments explain the pattern of results. The similarity in performance on these tasks of children with unrelated genetic disorders counters the view that numerical cognition is under any direct genetic control. Instead, our findings are consistent with the view that disturbances in foundational spatiotemporal cognitive functions contribute to the development of atypical representations and processes in the domains of basic magnitude comparison and simple numerical enumeration.

Purpose It seems to be the consensus (Zhang et al., 2012; George et al., 2003; Arumugam et al., 2013) that Lean Six Sigma (LSS) has become a beneficial improvement initiative used in a variety of industries. There is a move towards integrating any high-level business improvement methods holistically throughout the whole organisation. Indeed, Hoerl (2014) explored the idea that when using LSS for business improvement, the programme should engage the whole organisation in much the same way as the financial function is present throughout each department. The purpose of this paper is to posit that using the lean and green agenda may be the driver to achieve integration.Design/methodology/approach The research adopted a subjective ontological perspective with the researcher using participant observation as the main research instrument. Denzin and Lincoln (2005) note that it is now common for scholars to argue that the only relevant data are those based upon the personal experience of the researcher; this served as an informing foundation for the approach for the exploration of the topic. Based on multiple case studies, chosen because they operate in different sectors, the paper adopted an extended case method (Burawoy, 1998) to analyse and gather the research. The organisations were chosen because they both were at a similar stage in their continuous improvement (CI) journey. The main reasoning behind the selection of the two different organisations is to reach “Thick Description” (Geertz, 1973, p. 3, 2001).Findings The findings suggest that there are still significant benefits of implementing a large-scale lean agenda in particular when using an LSS methodology. The paper finds that there are also significant gaps in achieving full integration within the organisation and argues that lean and CI are still the remit of the operations manager. The document goes on to argue that if the CI initiative is driven by the corporate social responsibility (CSR) plan, then any lean/lean green implementation will enable the company to drive CI integration with all stakeholders.Research limitations/implications The research has implications for those responsible for the CSR function within the organisation and the operations manager who is charged with implementing any lean/lean and green CI.Practical implications The paper argues that the lean and green agenda can drive integration of any CI activity throughout the organisation and suggests that the way this can be achieved is any CI activity that is included in the wider CSR plan.Social implications This paper contributes to the “lean and green” agenda and offers a solution for the problem of integrating LSS activities throughout the whole organisation by placing CI and LSS within the CSR remit.Originality/value There is little consensus how this holistic integrated approach should be implemented by the company. This research uses multiple case studies to critically examine the application of LSS as an improvement programme within two large UK-based organisations, each company operating in very different industry sectors to identify the benefits of LSS but also the missed “green/societal” opportunities and argues that if any lean and lean and green agenda is to be holistically adopted, then any CI activity should be driven by the CSR department. [ABSTRACT FROM AUTHOR]

Purpose – The purpose of this paper is to suggest a solution to the problem of implementing a full “Lean” methodology for small-/medium-sized enterprises (SMEs) in a developing economy. Design/methodology/approach – This is a reflective paper that looks at an illustrative case study against the wider perspectives of the financial and resource costs of implementing a full lean programme in a developing country and suggests that using a “Lean Lite” approach may help the consultant/manager introduce lean concepts into a manufacturing organisation in a developing country. Findings – The paper concludes that “Lean Lite” as an approach that can be used to introduce lean initiatives in an SME in a developing economy by allowing a company with very limited resources to engage not only in business improvement but also in improving working conditions and education for employees. Research limitations/implications – The observations are limited to a single case study, although tempered by the authors’ wider experience. Further empirical research and critique of the original research is required to validate the observations and conclusions. Practical implications – The proposed “Lean Lite” initiative can help to introduce lean concepts to an organisation with limited financial and other resources. This helps organisations to increase productivity and assists the adoption of the lean philosophy and principles in a developing economy. The approach may also be used to engage in a wider corporate social responsibility strategy at ground level. Social implications – The social benefits as a result of implementing a Lean Lite approach include improving working conditions and educating employees. Originality/value – The paper proposes an approach that can be used to widen organisational involvement in lean initiatives in a developing economy by allowing a company with limited resources to engage not only in business improvement but also in improving working conditions and education for employees. As such the approach has both economic and social benefits. [ABSTRACT FROM AUTHOR]

Purpose – The purpose of this paper is to assess the current use being made of the sustainability message within business improvement activity and project justification within individual businesses. Design/methodology/approach – This is a reflective paper that looks at an illustrative case study against the wider perspectives of Lean Six Sigma (LSS) implementation, market orientation and business improvement initiatives in general. Findings – The piece discusses the gains derived from the LSS projects and identifies gaps in potential benefits in particular the paper questions how well any potential marketing messages were exploited by the organisation. The findings critically evaluates the impact that marketing function involvement could have in helping to promote the wider productivity message and its contribution to the wider corporate social responsibility (CSR) strategy for the organisation. The document also suggests how the company could leverage internally focused projects to adopt a companywide marketing orientation and use such leverage to support future LSS project selection and justification. Research limitations/implications – The observations are limited to a single case study, although tempered by the authors’ wider experience. Further empirical research is required to validate the observations and conclusions. Practical implications – The proposed approach to future improvement initiatives can help to increase the wider productivity message and assist organisations to exploit their internal projects in external communications and wider CSR strategy. Originality/value – The paper proposes an approach that can be used to widen organisational involvement in improvement initiatives allowing future project justification to be less internally cost focused, more holistic with a focus on customer voice. [ABSTRACT FROM AUTHOR]

Context: Nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) toxic effects, such as upper GI tract perforations, symptomatic gastroduodenal ulcers, and upper GI tract bleeding (PUBs), are thought to be attributable to cyclooxygenase 1 (COX-1) inhibition. Rofecoxib specifically inhibits COX-2 and has demonstrated a low potential for causing upper GI injury.Objective: To compare the incidence of PUBs in patients with osteoarthritis treated with rofecoxib vs NSAIDs.Design: Prespecified analysis of all 8 double-blind, randomized phase 2b/3 rofecoxib osteoarthritis trials conducted from December 1996 through March 1998, including one 6-week dose-ranging study, two 6-week efficacy studies vs ibuprofen and placebo, two 1-year efficacy studies vs diclofenac, two 6-month endoscopy studies vs ibuprofen and placebo, and one 6-week efficacy study vs nabumetone and placebo.Setting: Multinational sites. Participants Osteoarthritis patients (N = 5435; mean age, 63 years [range, 38-94 years]; 72.9% women).Interventions: Rofecoxib, 12.5, 25, or 50 mg/d (n = 1209, 1603, and 545, respectively, combined) vs ibuprofen, 800 mg 3 times per day (n = 847), diclofenac, 50 mg 3 times per day (n = 590); or nabumetone, 1500 mg/d (n = 127) (combined).Main Outcome Measure: Cumulative incidence of PUBs for rofecoxib vs NSAIDs, based on survival analysis of time to first PUB diagnosis, using PUBs that met pre-specified criteria judged by a blinded, external adjudication committee.Results: The incidence of PUBs over 12 months was significantly lower with rofecoxib vs NSAIDs (12-month cumulative incidence, 1.3% vs 1.8%; P = .046; rate per 100 patient-years, 1.33 vs 2.60; relative risk, 0.51; 95% confidence interval, 0.26-1.00). The cumulative incidence of dyspeptic GI adverse experiences was also lower with rofecoxib vs NSAIDS over 6 months (23.5% vs 25.5%; P = .02), after which the incidence rates converged.Conclusion: In a combined analysis of 8 trials of patients with osteoarthritis, treatment with rofecoxib was associated with a significantly lower incidence of PUBs than treatment with NSAIDs. [ABSTRACT FROM AUTHOR]

Purpose: Gastrointestinal microbleeding, as assessed by the measurement of (51)chromium-labeled red blood cells, is a marker of the mucosal injury associated with the use of nonsteroidal anti-inflammatory drugs. This study tested the hypotheses that cyclooxygenase-2 specific inhibition with rofecoxib would cause less fecal blood loss than a therapeutic dose of ibuprofen and would be equivalent to placebo.Subjects and Methods: In this randomized, double-blind group study, gastrointestinal blood loss was assessed by measurement of fecal (51)chromium radioactivity during a 1-week placebo baseline period and during 4 weeks of treatment with rofecoxib (25 mg or 50 mg once daily), ibuprofen (800 mg three times daily), or placebo in 67 healthy subjects. Gastrointestinal blood loss during treatment weeks 2 to 4 (versus the baseline period) was expressed as the geometric mean ratio of fecal radioactivity in weeks 2 to 4 compared with baseline.Results: Ibuprofen caused significantly (P <0.001) greater gastrointestinal blood loss (geometric mean ratio of 5.2, 95% confidence interval [CI]: 4.2 to 6.3) than the 25-mg dose of rofecoxib (2.6, 95% CI: 2.2 to 3.1), the 50-mg dose of rofecoxib (2.6, 95% CI: 2.2 to 3.0), or placebo (2.1, 95% CI: 1.8 to 2.5). In contrast, gastrointestinal blood loss with both doses of rofecoxib were equivalent to placebo by a predetermined clinical similarity bound.Conclusions: In healthy subjects, treatment with rofecoxib, at 2 to 4 times the doses that are currently recommended for the treatment of patients with osteoarthritis, produced significantly less fecal blood loss than a therapeutic dose of ibuprofen and was equivalent to placebo. [ABSTRACT FROM AUTHOR]

Background: Youth with chromosome 22q11.2 deletion syndrome (22q) face one of the highest genetic risk factors for the development of schizophrenia. Previous research suggests impairments in attentional control and potential interactions with elevated anxiety and reduced adaptive functioning may increase the risk for developing psychosis in this population. Here, we examined how variations in attentional control relate to the presence or severity of psychosis-proneness symptoms in these individuals., Methods: To achieve this, we measured attentional control in youth (12-18 years) with 22q (N = 35) compared to a typically developing group (N = 45), using a flanker task (the Distractor Target task) while measuring neural activity with event-related potentials., Results: Similar to previous findings observed in people with schizophrenia, greater attentional capture by, and reduced suppression of, non-target flanker stimuli characterized participants with 22q and was indexed by the N2pc (N2-posterior-contralateral) and P D (distractor positivity) components. Although we observed no relationships between these components and measures of psychosis-proneness in youth with 22q, these individuals endorsed a relatively low incidence of positive symptoms overall., Conclusions: Our results provide neural evidence of an attentional control impairment in youth with 22q that suggests these individuals experience sustained attentional focus on irrelevant information and reduced suppression of distracting stimuli in their environment. Impairments in attentional control might be a valid biomarker of the potential to develop attenuated positive symptoms or frank psychosis in high-risk individuals long before the age at which such symptoms typically arise. The evaluation of such a hypothesis, and the preventive potential for the putative biomarker, should be the focus of future studies., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Context: Patients treated with nonselective cyclooxygenase inhibitors (nonsteroidal anti-inflammatory drugs [NSAIDs]) often experience dyspepsia and upper gastrointestinal (GI) adverse effects, and frequently require GI comedications and diagnostic procedures., Objective: This study combined existing data to test the hypothesis that GI comedications and GI diagnostic procedures occur less frequently in osteoarthritis (OA) patients treated with rofecoxib compared with nonselective NSAIDs., Design: Combined analysis of 8 randomized controlled clinical trials., Setting: Rheumatology and general practice clinics., Patients: Men and women aged 40 years and older with OA., Interventions: Random assignment to placebo (n = 514), rofecoxib (n = 3357; 12.5, 25, or 50 mg daily combined; average 24.7 mg), or NSAIDs (n = 1564; ibuprofen 800 mg thrice daily, diclofenac 50 mg thrice daily, or nabumetone 1500 mg daily, combined)., Main Outcome Measures: The cumulative incidence of patients using GI comedications (antacids, antispasmodics, antiflatulents, antiregurgitants, H2 antagonists, proton pump inhibitors, sucralfate, prostaglandins, other antiulcer therapy) and needing GI procedures (upper GI barium studies, upper or lower GI endoscopies) over 12 months., Results: Compared with those treated with NSAIDs, patients treated with rofecoxib had a significantly lower incidence of GI comedication use (17.5% vs 27.0%, P <.001) and GI procedures (3.3% vs 5.3%, P =.02) over 12 months. Similar results were seen in analyses of protocols with placebo; in these studies, rates of GI comedications and procedures were highest with NSAIDs, while those with rofecoxib and placebo were similar to each other., Conclusions: OA patients treated with rofecoxib for up to 12 months required significantly less GI comedication and significantly fewer GI procedures than those treated with NSAIDs.

Background: Most nonsteroidal anti-inflammatory drugs (NSAIDs) are nonselective cyclooxygenase (COX-1 and COX-2) inhibitors and are associated with a variety of upper gastrointestinal (GI) tract symptoms. The roles of COX-1 and COX-2 in the pathogenesis of these symptoms are unclear. To test whether COX-2 inhibition with rofecoxib would have greater GI tolerability than nonselective COX-1 and COX-2 inhibition, we compared the incidences of (1) treatment discontinuations for GI adverse events (AEs) and (2) prespecified dyspeptic-type GI AEs among patients with osteoarthritis treated with rofecoxib vs NSAIDs., Methods: A prespecified, combined analysis of investigator-reported GI AEs in all 8 double-blind, randomized, phase 2b/3 osteoarthritis trials of rofecoxib was conducted. Patients included men and women with osteoarthritis (N = 5435); there was no upper age limit for entry. Treatments tested included rofecoxib, 12.5, 25, or 50 mg (combined), vs ibuprofen, diclofenac, or nabumetone (combined). Primary outcomes were the time (by survival analysis) to (1) treatment discontinuation due to GI AEs and (2) first reported dyspeptic-type GI AE. Between-treatment comparisons were made by log-rank test., Results: The number of treatment discontinuations caused by GI AEs during 12 months was significantly lower (P=.02) with rofecoxib vs NSAIDs (8.2 vs 12.0 per 100 patient-years; relative risk, 0.70; 95% confidence interval, 0.52-0.94). The incidence of prespecified dyspeptic-type GI AEs during the first 6 months was significantly lower (P=.02) with rofecoxib vs NSAIDs (69.3 vs 85.2 per 100 patient-years; relative risk, 0.85; 95% confidence interval, 0.74-0.97). However, the difference between treatments in dyspeptic-type GI AEs was attenuated after 6 months., Conclusion: Rofecoxib was associated with a lower incidence of treatment discontinuations due to GI AEs over 12 months and a lower incidence of dyspeptic-type GI AEs over 6 months than treatment with nonselective COX inhibitors, or NSAIDs. Arch Intern Med. 2000;160:2998-3003

Visual object enumeration is rapid and accurate for four or fewer items but slow and error-prone for over four items. This dichotomy has recently been linked to visual attentional phenomena by findings suggesting that 'subitizing' of small sets of objects is preattentive whereas 'counting' of over four items demands spatial shifts of attention. We evaluated this link at a neural level, using H2 15-O positron emission tomography to measure changes in regional cerebral blood flow while subjects enumerated the number of target vertical bars that 'popped out' of a 16-bar visual display consisting of both horizontal and vertical bars. Relative to a condition with a single target, subitizing (one to four targets) activated foci in the occipital extrastriate cortex, consistent with involvement of early, preattentive visual processes. Relative to subitizing, counting (five to eight targets) activated a widespread network of brain regions, including multiple foci implicated in shifting visual attention-large regions of the superior parietal cortex bilaterally and a focus in the right inferior frontal cortex. These results offer the first direct neural support for mapping the subitizing-counting dichotomy onto separable processes mediating preattentive vision and shifts of visual attention.

Objectives: This single-center, double-blind, randomized study assessed the effect of alendronate 5 and 10 mg on the gastroduodenal mucosa., Methods: Overall, 95 postmenopausal women without a recent history of major upper gastrointestinal (GI) disease and not taking gastric-irritant drugs, were screened with an upper GI endoscopy. Fourteen women (15% of the total) were found to have baseline endoscopic gastric and/or duodenal abnormalities, including mucosal hemorrhages (n = 4), erosions (n = 11), and ulcers (n = 3). Two additional women had baseline esophageal abnormalities. Thus, 79 postmenopausal women (mean age 51 yr, range 41-64 yr), free of esophageal, gastric and/or duodenal erosions or ulcer, were enrolled. Subjects received placebo, alendronate 5 mg/day or 10 mg/day, or aspirin 650 mg q.i.d. for 14 days. Endoscopy was repeated on Day 8 and on Day 15. Gastric and duodenal mucosae were graded separately using a 5-point scale for erosive mucosal injury., Results: The proportions of subjects with a gastric or duodenal erosion score > or = 2 (presence of at least one mucosal erosion) on either Day 8 or 15 were four of 22 (18.2%) in the placebo group; four of 22 (18.2%) in the alendronate 5 mg group; five of 21 (23.8%) in the alendronate 10 mg group; and 14 of 14 (100.0%) in the aspirin group. Thirty-five of 76 (46%) subjects were H. pylori-positive (Pyloritek test), and were equally distributed across treatment groups., Conclusions: Alendronate 5 and 10 mg/day for 2 wk was associated with a lower incidence of gastric erosions than aspirin. The incidence of gastric erosions in the alendronate groups did not differ significantly from the placebo group. In this study, unlike aspirin, alendronate did not induce gastric erosions.

We investigated the neurobiological basis of visual processes involved in object enumeration. Subitizing, the ability to rapidly and accurately enumerate four or fewer objects, is thought to depend on preattentive processing of visual stimuli, whereas counting of more numerous objects is thought to require serial shifts of attention. We attempted to distinguish between the hypothesis that the magnocellular (M) visual pathway is the preferential route for subitizing, and the alternative hypothesis that there is no selectivity for the M pathway or its counterpart, the parvocellular (P) visual pathway, in visual object enumeration. Green rectangles were presented on an equiluminant red background to impair M pathway processing. This slowed enumeration performance relative to a control condition in which object/background luminance differed, especially when the rectangles were relatively large and widely spaced and had constant retinal eccentricity. When low luminance contrast was used to impair processing along the P pathway, enumeration performance was slowed relative to a high-contrast control condition, especially when the rectangles were small and closely spaced. Overall, our manipulations affected enumeration performance without selectivity for subitizing or counting ranges and without altering the slope of the functions relating reaction time to numerosity. Thus, our results favor the hypothesis that visual enumeration does not depend preferentially on either the M or the P pathway.

Background & Aims: Leukotrienes (LTs) are believed to be important in the pathogenesis of ulcerative colitis (UC). The aim of this study was to determine whether inhibition of LT biosynthesis with a 5-lipoxygenase inhibitor (MK-591) induces remission in patients with mild to moderate UC., Methods: One hundred eighty-three patients with mild to moderately active UC enrolled in this randomized parallel group, double-blind study. Patients received placebo or MK-591 at a dose of 12.5, 50, or 100 mg twice daily for 8 weeks. A subset of patients underwent rectal dialysis to determine LTB4 concentration., Results: MK-591 reduced LTB4 concentrations in rectal dialysate at the final determination. The median percent of baseline LTB4 concentration for 100 mg taken twice daily was 1.4% (n = 4); for 50 mg taken twice daily, 16.5% (n = 6); for 12.5 mg taken twice daily, 12% (n = 6); and for placebo, 78% (n = 6). There was no correlation between reduction of LTB4 and remission. Patients in remission at week 8 were as follows: placebo, 9 of 44 (20.5%); 100 mg taken twice daily, 11 of 43 (25.6%); 50 mg taken twice daily, 8 of 49 (16.3%); and 12.5 mg taken twice daily, 4 of 47 (8.5%) (P > 0.10)., Conclusions: MK-591 markedly inhibited LT biosynthesis, but it did not differ significantly from placebo in clinical efficacy. Inhibition of LT biosynthesis was not effective as a single therapeutic modality in active UC.

Objective: The purpose of this multicenter, randomized, double-blind study, conducted in 520 patients, was to compare the efficacy and safety of omeprazole (40 and 20 mg once daily) with placebo in the treatment of benign gastric ulcer., Methods: Treatment with omeprazole or placebo lasted 4 wk; those whose ulcers remained unhealed continued the same treatment regimen for an additional 4 wk. The effects of therapy were determined by endoscopy and assessment of GI symptoms. Safety and tolerability were evaluated through reported adverse events, physical examinations, and laboratory tests., Results: At weeks 4 and 8, the proportion of patients with healed ulcers was significantly greater in the omeprazole 40- and 20-mg groups than in the placebo group (p < 0.01). At week 8, the healing rate was significantly greater in the 40-mg group than in the 20-mg group (82.7 vs 74.8%, p < 0.05). In patients with large ulcers (>1 cm), the 40-mg regimen was associated with a significantly higher healing rate (78.9%) than both the 20-mg regimen (61.4%) and placebo (34.6%) at week 8 (p < 0.05 vs omeprazole 20 mg; p < 0.01 vs placebo). Healing rates in patients with small ulcers were similar for the 40- and 20-mg groups. Omeprazole was well tolerated, with no significant differences versus placebo in the overall incidence of clinical or laboratory adverse events., Conclusions: Omeprazole 40 and 20 mg, administered once daily, healed a significantly greater proportion of patients than did placebo. The 40-mg regimen offered significant advantages over the 20-mg regimen in patients with large ulcers.

Two experiments showed that, when selective eye movements were disabled by the presentation of stimuli in the form of afterimages, increased inspection time and facilitative stimulus configurations failed to increase the subitizing limit of 4 objects. Afterimages of two to eight dots induced by a photographic flashgun were shown to 3 adult subjects. For more than 4 objects, enumeration errors occurred at a rate of 20%-30%. Enumeration was effectively perfect for 2-4 linearly configured dots, with occasional errors surprisingly occurring in that range when dots appeared in groups of up to 3 items. No errors occurred in nonafterimage control conditions. Enumeration errors were attributed to failures of individuating dots to be counted due to the deactivation of selective eye movements in afterimages. A third experiment supported this interpretation by disabling eye movements with briefly presented stimuli and producing results much like those of the afterimage conditions.

Background: Acid suppression with famotidine, a histamine H2-receptor antagonist, provides protection against gastric injury in normal subjects receiving short courses of aspirin or naproxen. The efficacy of famotidine in preventing peptic ulcers in patients receiving long-term therapy with nonsteroidal antiinflammatory drugs (NSAIDs) is not known., Methods: We studied the efficacy of two doses of famotidine (20 mg and 40 mg, each given orally twice daily), as compared with placebo, in preventing peptic ulcers in 285 patients without peptic ulcers who were receiving long-term NSAID therapy for rheumatoid arthritis (82 percent) or osteoarthritis (18 percent). The patients were evaluated clinically and by endoscopy at base line and after 4, 12, and 24 weeks of treatment. The evaluators were unaware of the treatment assignment. The primary end point was the cumulative incidence of gastric or duodenal ulceration at 24 weeks., Results: The cumulative incidence of gastric ulcers was 20 percent in the placebo group, 13 percent in the group of patients receiving 20 mg of famotidine twice daily (P = 0.24 for the comparison with placebo), and 8 percent in the group receiving 40 mg of famotidine twice daily (P = 0.03 for the comparison with placebo). The proportion of patients in whom duodenal ulcers developed was significantly lower with both doses of famotidine than with placebo (13 percent in the placebo group, 4 percent in the low-dose famotidine group [P = 0.04], and 2 percent in the high-dose famotidine group [P = 0.01]). Both doses of famotidine were well tolerated., Conclusions: Treatment with high-dose famotidine significantly reduces the cumulative incidence of both gastric and duodenal ulcers in patients with arthritis receiving long-term NSAID therapy.

The tolerability of omeprazole was compared to control agents in 68 clinical studies that enrolled a total of 4846 patients, of whom 3096 received omeprazole. The incidence of adverse experiences was independent of omeprazole dose administered, the age of the patients, and the disease treated (duodenal ulcer or endoscopically verified gastroesophageal reflux disease). The most common clinical adverse experiences were headache, diarrhea, abdominal pain, and nausea. The most common laboratory adverse experiences were elevated aspartate aminotransferase and elevated alanine aminotransferase. Omeprazole was well tolerated, and the incidence of clinical and laboratory adverse experiences was similar in patients receiving omeprazole, placebo, cimetidine, or ranitidine.

Purified plasma membrane fractions of cultured well-differentiated Reuber H35 hepatoma cells were studied after growth in the presence or absence of ethanol. Growth of cells in the presence of ethanol significantly increased plasma membrane 5'-nucleotidase activity but did not influence sodium-potassium adenosinetriphosphatase activity. Fluorescence polarization of lipophilic probes was used to study membrane lipid structure. Steady-state polarization of diphenylhexatriene (DPH), a probe of the hydrophobic core, was significantly lower in plasma membranes from cells grown in 80 mM ethanol for 3 weeks, compared to controls. Decreased polarization of DPH in plasma membranes was observed after 3-weeks growth of cells in as little as 1 mM ethanol. A 1-h exposure to 80 mM ethanol had no effect. Altered DPH polarization was due to a decrease in the order parameter of the probe. The rotational correlation time of the probe was virtually unchanged. Chronic ethanol treatment of cells did not alter the polarization of the membrane surface probe trimethylammoniodiphenylhexatriene. Plasma membranes from cells grown in 80 mM ethanol had decreased contents of both phospholipid and unesterified cholesterol, but the cholesterol to phospholipid ratio was unchanged. The percentages of sphingomyelin and phosphatidylserine in plasma membrane phospholipids were significantly decreased after ethanol treatment, while the phosphatidylcholine/sphingomyelin ratio was increased by 42%. Vesicles prepared from total plasma membrane lipids of ethanol-treated cells, as well as vesicles prepared from polar lipids alone, showed the same alterations in DPH polarization as did plasma membranes. The importance of ethanol metabolism in the observed plasma membrane changes was demonstrated in two ways.(ABSTRACT TRUNCATED AT 250 WORDS)

Endonuclease V of bacteriophage T4 binds to UV-irradiated deoxyribonucleic acid (DNA) but not to unirradiated DNA. We have developed an assay to detect this binding, based on the retention of enzyme--DNA complexes on nitrocellulose filters. The amount of complex retained, ascertained by using radioactive DNA, is a measure of T4 endonuclease V activity. The assay is simple, rapid, and specific, which makes it useful for detecting T4 endonuclease V activity both in crude lysates and in purified preparations. We have used it to monitor enzyme activity during purification and to study binding of the enzyme to DNA under conditions that minimize the ability of the enzyme to nick DNA. From our data we conclude that (1) T4 endonuclease V binds to UV-irradiated DNA but not to DNA that has been previously incised by the endonuclease, (2) equilibrium between the free and complexed form of the enzyme is attained under our reaction conditions, (3) dissociation of enzyme--DNA complexes is retarded by sodium cyanide, and (4) retention of enzyme--DNA complexes on nitrocellulose filters is enhanced by high concentrations of saline--citrate.

Previous studies have indicated that the ultraviolet endonuclease of bacteriophage T4 acts specifically at pyrimidine dimer sites in ultraviolet-irradiated DNA. At such sites the enzyme could conceivably catalyze endonucleolytic incision of the DNA either on the dimer-containing strand or on the strand directly opposite to the dimer. In the present work, a direct test of these alternatives was made. Substrate molecules containing one irradiated and one unirradiated strand were prepared from differentially isotopically labeled purified complementary strands of bacteriophage lambdaDNA. Following incubation with the enzyme, the sedimentation profiles of the DNA strands in alkaline sucrose density gradients were compared. The results show that the enzyme selectively nicks the irradiated strand.

We have examined the modes of DNA synthesis in Escherichia coli strains made permeable to nucleoside triphosphates by treatment with toluene. In this quasi in vitro system, polymerase-I-deficient mutants exhibit a nonconservative mode of synthesis with properties expected for the resynthesis step of excision-repair. This UV-stimulated DNA synthesis can be performed by either DNA polymerase II or III and it also requires the uvrA gene product. It requires the four deoxynucleoside triphosphates; but, in contrast to the semiconservative mode, the ATP requirement can be partially satisfied by other nucleoside triphosphates. The ATP-dependent recBC nuclease is not involved. The observed UV-stimulated mode of DNA synthesis may be part of an alternate excision-repair mechanism which supplements or complements DNA-polymerase-I-dependent repair in vivo.

Two hundred and sixty monolinguals divided into subgroups based on gender, handedness, and familial left-handedness, were given a concurrent task, verbal-manual interference paradigm. The primary purpose of the study was to test whether the dual task interference effects were more related to hemispheric speech or manual dominance factors. The dominant hand, regardless of handedness, underwent relatively more tapping interference than the nondominant hand. The obtained results seriously question the basic assumptions underlying the interpretation of the dual task paradigm as an assessment index for hemispheric language lateralization. A possible explanation of this result that is in keeping with known hemispheric language representation proportions in left-handers is offered based on left hemisphere ipsilateral control of the left hand.