Search

The self-healing of five geosynthetic clay liners (GCLs) with laboratory simulated down-slope erosion defects (quasi-circular holes and linear slits where there is little or no bentonite) upon hydration from Godfrey silty sand subgrade with wfdn = 16% under an overburden stress σv = 20 and 100 kPa is examined. While there was an up to 9.6 mm reduction in hole diameter/slit width, none of the defects fully self-healed. The self-healing of these laboratory eroded specimens with a swell index of 10.2 ± 1.7 ml/2 g after hydration is generally smaller than that of the corresponding virgin GCLs. GCLs with powdered bentonite with an initial SI of 32 ml/2 g generally self-healed better and the intact specimens had a lower hydraulic conductivity than GCLs with granular bentonite with an initial SI of 24–26 ml/2 g. Higher mass per unit area of bentonite and overburden stress led to better self-healing. Ponding of distilled (DI) water above the GCL increased self-healing of GCL slightly more than simulated synthetic landfill leachate (SSL). The post-hydration hydraulic conductivity, k, of GCL specimens with holes/slits is shown to be about 1–3 orders of magnitude higher than that of the intact GCL specimen.

The self-healing of fully penetrating artificial defects (circular holes and rectangular slits) in geosynthetic clay liners (GCLs) on full hydration in deionized water and 10 mM calcium chloride (CaCl2) solution under 2 kPa overburden stress are compared. Circular holes with diameters up to 41 mm self-healed in deionized water but with an indentation of about up to 2 mm deep remaining at the center of the larger self-healed zones for holes of 30 mm diameter and larger. Holes of up to 35 mm diameter completely closed-up in 10 mM CaCl2 solution, but with an indentation of about up to 6 mm deep remaining at the center of the larger self-healed zones for holes of 30 mm diameter and larger. A fully penetrating 15 mm wide × 120 mm long single slit in the center of a GCL specimen completely closed up in deionized water but not in 10 mM CaCl2 solution. Even in deionized water, the slit does not fully close when 25 mm (or more) wide. Double parallel silts 15 mm wide × 240 mm long closed up in deionized water, but not in 10 mM CaCl2 solution when there was a 20 mm-wide strip of undamaged GCL between the slits, but did not fully close up when the undamaged GCL strip between the slits was reduced to 10 mm or 5 mm. The difference in self-healing based on the hydrating fluid chemistry is discussed.

BackgroundVaccination against SAR-CoV-2 is a new campaign and believed to be the key to end the pandemic. Currently, there are two COVID-19 vaccines with different mechanism of action available in Hong Kong - they are the inactivated virus vaccine and the mRNA-based vaccine. Both vaccines have obtained approval for emergency use by the World Health Organization (WHO) and were widely deployed globally (1). A mass voluntary vaccination program for all Hong Kong residents has started in late February, 2021 (2). However, the efficacy and safety of COVID-19 vaccines in patients with SLE is uncertain due to a complex interplay of underlying autoimmunity and immunosuppressive therapies used.ObjectivesThis study was to investigate the effects of both inactivated and mRNA COVID-19 vaccines in patients with SLE.MethodsThis was a prospective, single-centre, case-control study. Patients with SLE planning to receive COVID-19 vaccines were recruited and matched 1:1 with healthy controls. The immunogenicity of the COVID-19 vaccines was assessed by a surrogate neutralization assay at 28 days after the second dose. The main outcomes included the antibody response and adverse effects comparing SLE patients and controls. Predictors of responses in SLE patients were analyzed. The change of SLE disease activity was evaluated.ResultsSixty-five SLE patients received 2 doses of COVID-19 vaccines (Comirnaty: 38; CoronaVac: 27) were recruited. Many of them were on systemic glucocorticoids (75.8%) and immunosuppressants (54.5%). At day 28 after the second dose of vaccines, 92.3% (Comirnaty: 100%; CoronaVac: 81.5%, p=0.01) had positive neutralizing antibody. However, compared to the age, gender, vaccine type matched controls, the level of neutralizing antibody was significantly lower (pTable 1.Multivariate linear regression analysis for neutralizing antibody activityBeta95% confidence intervalP valueAge-0.022-0.425 – 0.3810.914Gender8.1625 (92.6)0.296SLEDAI-2k-1.96-4.22 – 0.310.088Prednisolone dosage-2.01-3.66 - -0.370.018Mycophenolate mofetil-15.2-24.4 - -6.00.002Type of vaccines: Comirnaty28.820.1 – 37.5Figure 1.Distribution of neutralizing antibody levels after COVID-19 vaccines comparing (A) SLE patients and matched controls, (B) SLE patients and matched controls in two vaccine subgroups, and (C) two vaccine types in SLE patients. Data for each group are presented as box plots: central values within boxes correspond to median; the range between the lower (Q1) and upper (Q3) bounds of the boxes is the IQR. Whiskers represent scores outside IQR and ends in maximum (higher “calculated value” = Q3 + 1.5 x IQR) and minimum (lower “calculated value” = Q1 – 1.5 x IQR). Spots are outliers above the maximum or under the minimum values. Data regarding were analyzed using Mann-Whitney-U test. Dotted line denotes the cut-off level for positivity (30%).ConclusionCOVID-19 vaccines produced satisfactory but impaired serological response in SLE patients compared to controls which was dependent on the immunosuppressive medications use and type of vaccines received. There was no new short-term safety signal noted. Booster dose is recommended.References[1]Wouters OJ, Shadlen KC, Salcher-Konrad M, Pollard AJ, Larson HJ, Teerawattananon Y, et al. Challenges in ensuring global access to COVID-19 vaccines: production, affordability, allocation, and deployment. Lancet. 2021;397(10278):1023-34.[2]COVID-19 Vaccination Programme.Disclosure of InterestsNone declared

BackgroundAxial spondyloarthritis (axSpA) patients had a higher risk of cardiovascular disease (CVD) than the general population (1). It is also suggested that inflammation, rather than a particular disease, drives the increased risk of CVD (2). But the relationship between inflammation in axSpA and CVD is unknown.ObjectivesTo examine whether inflammatory burden over time can predict cardiovascular events (CVE) independent of baseline CV risk factors in axial spondyloarthritis (axSpA) patients.MethodsA cohort analysis was performed in patients who had been recruited since January 2001. The primary outcome was a first CVE occurring between January 2001 and December 2020. Three CVD risk scores were computed at baseline. The performance of the original and modified (x 1.5 multiplication factor) CV risk algorithms were assessed. Time-varying Cox proportional hazard models and Kaplan-Meier survival analysis were used to assess whether inflammatory burden (Bath ankylosing spondylitis disease activity index [BASDAI] and inflammatory markers), non-steroidal anti-inflammatory drugs (NSAIDs) and disease modifying anti-rheumatic drugs (DMARDs) can predict the development of first CVE.Results463 patients [35(26-45) years, male: 360(77.8%)] were recruited. After a median follow up of 12 (7-19) years, 61 patients (13.2%) experienced a first CVE. Traditional/modified CV risk scores underestimated CV risk. Erythrocyte sedimentation rate (ESR)≥20 mm/hr was associated with a significantly higher risk of CVE during follow-up [HR: 2.07, 95%CI (1.10, 3.98), p=0.008]. Active disease as indicated by a rising BASDAI also showed positive trend towards a higher risk of developing CVE over time. After adjusting for CV risk scores in the multivariable models, high ESR level (ESR≥20 mm/hr) over time remained significantly associated with a higher risk of developing CV events (Table 1a and 1b). A significant difference in the CV event-free survival between patients with ESR≥20 mm/hr and ESRTable 1.Multivariable analysis with time-dependent Cox proportional hazard regression for the predictors of cardiovascular events.Figure 1.Kaplan-Meier survival analysis between time-varying ESR level and CVE. P=0.006 for difference in CVE-free survival rate between patients with ESR≥20mm/hr and ESRConclusionIncreased inflammatory burden as reflected by elevated ESR levels (ESR≥20) was associated with increased risk of CVE, while the use of NSAIDs and DMARDs were not.References[1]Exarchou, S., et al., Mortality in ankylosing spondylitis: results from a nationwide population-based study. Ann Rheum Dis, 2016. 75(8): p. 1466-72.[2]Lauper, K., et al., Incidence and Prevalence of Major Adverse Cardiovascular Events in Rheumatoid Arthritis, Psoriatic Arthritis, and Axial Spondyloarthritis. Arthritis Care & Research, 2018. 70(12): p. 1756-1763.Table 1a.Model 1Model 2Model 3Time-dependent HR (95%CI)p-valueTime-dependent HR (95%CI)P-valueTime-dependent HR (95%CI)P-valueESR≥202.75 (1.23, 6.14)0.014*2.74 (1.21, 6.21)0.016*2.93 (1.31, 6.57)0.009*BASDAI1.07 (0.90, 1.28)0.4551.06 (0.88, 1.28)0.5191.07 (0.89, 1.28)0.442FRS1.06 (1.03, 1.09)QRISK31.05 (0.99, 1.11)0.132SCORE1.25 (1.09, 1.42)0.001*Table 1b.Model 1Model 2Model 3Time-dependent HR (95%CI)P-valueTime-dependent HR (95%CI)P-valueTime-dependent HR (95%CI)P-valueESR≥202.77 (1.24, 6.18)0.013*2.78 (1.23, 6.28)0.014*2.95 (1.32, 6.59)0.008*BASDAI≥41.37 (0.62, 2.99)0.4341.26 (0.58, 2.78)0.5591.42 (0.65, 3.09)0.376FRS1.06 (1.03, 1.09)QRISK31.05 (0.99, 1.11)0.138SCORE1.24 (1.09, 1.42)0.001**Statistically significant at p≤0.05.HR, hazard ratio; BASDAI: Bath Ankylosing Spondylitis Disease Activity Index; CRP: C-Reactive Protein; ESR: Erythrocyte Sedimentation Rate; FRS: Framingham Risk Score; SCORE: Systematic Coronary Risk Evaluation.AcknowledgementsWe would like to show our gratitude to all medical staffs, research assistants.Disclosure of InterestsNone declared

BackgroundPatients with systemic lupus erythematosus (SLE) are at increased risk of severe COVID-19 due to the underlying disease, comorbidities and use of immunosuppressants (IS). An alternative option would be to adopt telemedicine (TM) to maintain medical care while minimizing exposure. Despite being widely adopted during the pandemic, the evidence supporting the use of TM in rheumatology has been limited.ObjectivesWe primarily aimed to evaluate the effectiveness to maintain disease activity control using TM delivered care compared to conventional in-person follow-up in patients with lupus nephritis (LN). The secondary objectives were to compare the patient reported outcomes, safety and cost-of-illness from the patient’s perspective between the 2 modes of health care delivery.MethodsThis was a 1-year, single-center, RCT conducted at a regional hospital in Hong Kong. From May 2020, consecutive adult patients with a SLE according to the 2019 EULAR/ACR classification criteria followed up at the LN clinic were invited to participate in the study. Participants were randomized 1:1 to either TM (TM group) or standard FU (SF group). Patients randomized to receive TM FU were scheduled for a video consultation via a commerical software ZOOM. Patients in the SF group received standard in-person outpatient care. SLE disease activity at each consultation was assessed by SLEDAI-2k and physician global assessment (PGA).ResultsA total of 144 patients with LN were randomized and 3 patients self-withdrew from the study. The mean age was 44.5±11.4 years and the median time from diagnosis to randomization was 168 months (range: 1-528). Most of the patients had class III, IV or V LN (87.2%) and were on prednisolone (89.4%, median dose 5mg daily). Many of them (68.1%) were on IS. While 66.0% of the patients were in lupus low disease activity state (LLDAS), none had disease remission. There were no baseline differences, including demographics, SLEDAI-2k (TM: 3.8±2.3, SF: 3.2±2.2, p=0.13, PGA (TM: 6.2±6.5, SF: 4.6±5.9, p=0.13) and SLE damage index (TM: 1.1±1.3, SF: 0.8±1.1, p=0.10), between the 2 groups.At one year, 80.0% and 80.2% of the patients in the TM group and SF group were in LLDAS or remission respectively. SLE disease activity indices including SLEDAI-2k, PGA, proteinuria amount and serum anti-ds-DNA level remained similar between the 2 groups. Within the study period, 28 (40%) patients in the TM group and 21 (29.6%) patients in the SF group had disease flare (p=0.20). There were no differences in the SF-36, lupusQoL and HADS scores between the 2 groups at the end of the study. The overall patient satisfaction score was higher in the TM group with a significantly shorter waiting time before seeing doctors. At the end of the study, 67.9% of the overall participants agreed to (versus 15.0% who did not agree to) use TM as a mode of future FU.The mean indirect costs of illness (HKD26,681 vs HKD12,016, p=0.20) and the out-of-pocket costs for health care services were similar between the 2 groups (TM: HKD13,547 vs SF: HKD12,297, p=0.83) in one year. The total number of FU was similar (TM: 6.0±2.0, SF: 5.7±1.7, p=0.40). However, significantly more patients in the TM group (29/70, 41.4% vs 4/71, 5.6%; pp=0.02). After adjusting for age and prednisolone dosage, not being in LLDAS at baseline was the predictor of hospitalization (OR 3.4, 95%CI 1.20-9.65). None of the participants was tested positive for COVID-19.ConclusionTM FU resulted in similar 1-year disease activity control and better satisfaction in patients with LN compared to standard care. However, a significant proportion of patients cared by TM required in-person visits or were hospitalized. The results of the study suggest that TM delivered care could help minimizing exposure to COVID-19, but it needs to be complemented by physical visits, particularly in those with unstable disease.AcknowledgementsWe would also like to thank the University of Central Lancashire & East Lancashire Hospitals NHS Trust for granting us permission to use the LupusQoL questionnaire.Disclosure of InterestsNone declared

BackgroundAxial spondyloarthritis (axSpA) patients have increased risks of developing cardiovascular diseases (CVD) compared to the general population. Hypertension (HT) as the most common CV risk factor in these patients. Whether chronic, low-grade inflammation predispose to the development of incident hypertension in axSpA remained uncertain.ObjectivesTo examine the association between markers of systemic inflammation and incident hypertension in axSpA patients.MethodsA cohort analysis was performed in patients with axSpA who had been followed since January 2001. Patients diagnosed with hypertension and/or on anti-hypertensives at baseline were excluded. The primary outcome was first diagnosis of HT occurring between January 2001 and December 2020. Three different CVD risk scores including Framingham risk score (FRS), QRISK3 and SCORE were computed at baseline. Baseline demographic data and clinical inflammatory and disease activity parameters were assessed using Cox proportional hazard regression. The association between disease activity measures, inflammatory markers, medications, and the occurrence of incident HT was assessed using time-varying Cox proportional hazard models after adjusting for baseline CVD risk scores.Results413 patients [34(25-43) years, male: 319 (77.2%)] were recruited. After a median follow up of 12 (6-17) years, 58 patients (14%) developed incident HT (IHT+group). In baseline multivariable Cox regression analysis, ESR and CV risk scores were significantly associated with developing IHT (pTable 1.Multivariable analysis with Cox proportional hazard regression for the baseline predictors of incident HT.Model 1Model 2HR (95%CI)p-valueHR (95%CI)P-valueBASDAI≥51.44 (0.78, 2.67)0.2441.39 (0.75, 2.59)0.3ESR1.01 (1.00, 1.02)0.003*1.01 (1.00, 1.02)0.003*BASFI1.03 (1.00, 1.02)0.6161.03 (0.92, 1.16)0.572Baseline disease duration1.04 (1.00, 1.08)0.1021.03 (0.98, 1.08)0.215Symptom duration1.01 (0.98, 1.05)0.5131.02 (0.98, 1.05)0.386FRS1.05 (1.03, 1.08)SCORE1.23 (1.12, 1.36)Table 1b.Model 1Model 2HR (95%CI)p-valueHR (95%CI)P-valueBASDAI≥61.53 (0.84, 2.78)0.1661.47 (0.81, 2.69)0.209ESR1.01 (1.00, 1.02)0.003*1.01 (1.00, 1.02)0.003*BASFI1.03 (0.92, 1,15)0.6461.03 (0.92, 1.16)0.599Baseline disease duration1.04 (1.00, 1.08)0.1211.03 (0.98, 1.07)0.244Symptom duration1.01 (0.98, 1.05)0.5301.02 (0.98, 1.05)0.391FRS1.05 (1.03, 1.08)SCORE1.23 (1.11, 1.35)ConclusionHigher baseline and time-varying inflammatory burden predict the development of IHT in addition to traditional CV risk scores in axSpA patients. While exposure to csDMARDs may be associated with the development of IHT, NSAIDs and biologic DMARDs use were not associated with the development of IHT.References[1]Exarchou, S., et al., Mortality in ankylosing spondylitis: results from a nationwide population-based study. Ann Rheum Dis, 2016. 75(8): p. 1466-72.Table 2.Multivariable analysis with Cox proportional hazard regression for the time-dependent predictors of incident HT.Table 2a.Model 1Model 2Time-dependent HR (95%CI)p-valueTime-dependent HR (95%CI)P-valueESR1.01 (1.00, 1.03)0.0851.01 (1.00, 1.03)0.074csDMARDs2.24 (1.04, 4.82)0.04*2.16 (1.00, 4.68)0.05FRS1.05 (1.01, 1.08)0.008*SCORE1.24 (1.09 1.41)0.001*Table 2b.Model 1Model 2Time-dependent HR (95%CI)P-valueTime-dependent HR (95%CI)P-valueESR≥202.22 (1.05, 4.72)0.038*2.27 (1.06,4.82)0.034*csDMARDs2.17 (1.01, 4.64)0.047*2.09 (0.97, 4.50)0.059FRS1.05 (1.01, 1.08)0.01*SCORE1.23 (1.08, 1.41)0.002*Disclosure of InterestsNone declared

Recent research has suggested that the visual span in stimulus identification can be enlarged through perceptual learning. Since both English and music reading involve left-to-right sequential symbol processing, music-reading experience may enhance symbol identification through perceptual learning particularly in the right visual field (RVF). In contrast, as Chinese can be read in all directions, and components of Chinese characters do not consistently form a left-right structure, this hypothesized RVF enhancement effect may be limited in Chinese character identification. To test these hypotheses, here we recruited musicians and nonmusicians who read Chinese as their first language (L1) and English as their second language (L2) to identify music notes, English letters, Chinese characters, and novel symbols (Tibetan letters) presented at different eccentricities and visual field locations on the screen while maintaining central fixation. We found that in English letter identification, significantly more musicians achieved above-chance performance in the center-RVF locations than nonmusicians. This effect was not observed in Chinese character or novel symbol identification. We also found that in music note identification, musicians outperformed nonmusicians in accuracy in the center-RVF condition, consistent with the RVF enhancement effect in the visual span observed in English-letter identification. These results suggest that the modulation of music-reading experience on the visual span for stimulus identification depends on the similarities in the perceptual processes involved.

Background:Partial repair of bone erosions in rheumatoid arthritis (RA) is known from high-resolution peripheral quantitative computer tomography (HR-pQCT) studies in patients with moderate to high disease activity using biologics [1]. Whether RANKL inhibition by denosumab is efficacious in healing existing erosions in RA patients with low disease activity or in remission on conventional synthetic DMARDs is uncertain.Objectives:To evaluate the effects of denosumab on erosion healing at 2-4 metacarpophalangeal head as determined by HR-pQCT in patients with RA with stable disease.Methods:This was a randomized, placebo-controlled, double-blind study. RA patients with disease activity score 28 joints (DAS28) ≤5.1 were randomized (1:1) to subcutaneous denosumab 60 mg or placebo once every six months for 24 months. The primary outcome was erosion healing at MCP 2-4 on HR-pQCT at 12 months. The effects of denosumab on erosion and joint space parameters on HR-pQCT and radiographs, disease activity and health assessment questionnaire-disability index (HAQ-DI) were also examined.Results:At 24 months, HR-pQCT images were analyzed in 98 patients. Baseline demographic, clinical characteristics and imaging parameters were comparable between the two treatment groups (table 1). Seventeen patients in each group (placebo group: 17/52, 32.6%; denosumab group: 17/50, 34.0%) achieved sustained low disease activity (DAS28 ≤ 3.2) throughout the 24 months. At 12 months, changes in erosion parameters on HR-pQCT were similar between the two groups. At 24 months, new erosions (19% vs 9%, p=0.009) and erosion progression (34% vs 16%, pTable 1.Baseline clinical, demographic, disease activity parameters and medicationsPlacebo (n=55)Denosumab (n=55)Total (n=110)Age56.5 ± 7.157.2 ± 8.556.8 ± 7.8Gender (Female)47 (86)41 (75)88 (80)Disease duration (years)8.5 ± 6.87.3 ± 6.97.9 ± 6.8Rheumatoid factor positive40 (72)38 (69)78 (71)ACPA positive43 (78)44 (80)87 (79)DAS28-CRP2.43 ± 0.832.6 ± 0.922.51 ± 0.88DAS28-CRP>3.28 (15)13 (24)21 (19)HAQ-DI (0-3)0.31 ± 0.380.46 ± 0.470.39 ± 0.43csDMARDs49 (89)52 (95)101 (92)Combination csDMARDs26 (47)33 (60)59 (54)Glucocorticoids5 (10)5 (9)10 (9)vdH- Sharp erosion score10.4 ± 18.48.9 ± 13.89.6 ± 16.2vdH- Sharp JSN score12.4 ± 17.711.5 ± 17.211.9 ± 17.4Lumbar spine aBMD, g/cm20.914 ± 0.1470.930 ± 0.1430.922 ± 0.145Total hip aBMD, g/cm20.837 ± 0.1020.847 ± 0.1460.841 ± 0.125Femoral neck aBMD, g/cm20.681 ± 0.0990.695 ± 0.1280.687 ± 0.114Data are reported as mean ± SD or number (%). ACPA: Anti-cyclic citrullinated peptide antibody; DAS28: disease activity score 28; csDMARDs: conventional synthetic disease modifying anti-rheumatic drug. HAQ-DI: health assessment questionnaire disability index; vdH- Sharp score: Van der Heijde- Sharp score; aBMD: areal bone mineral densityConclusion:Although no differences in erosion parameters were observed at 12 months, denosumab was more efficacious than placebo in erosion repair on HR-pQCT after 24 months.References:[1]Finzel S, Rech J, Schmidt S, et al. Interleukin-6 receptor blockade induces limited repair of bone erosions in rheumatoid arthritis: a micro CT study. Ann Rheum Dis 2013;72:396-400.Figure 1.Changes in erosion parameters by HR-pQCT. (A) Percentage of patients with overall erosion healing; (B) Outcome of individual erosion with healing, progression and new erosion detected across study period; change in (C) mean erosion volume; (D) total erosion volume; (E) erosion width; (F) erosion depth and (G) marginal osteosclerosis per patient.Disclosure of Interests:Ho SO: None declared, Isaac T. Cheng: None declared, Sze-Lok Lau: None declared, Evelyn Chow: None declared, Tommy Lam: None declared, Vivian W Hung: None declared, Edmund Li: None declared, James F Griffith: None declared, Vivian WY Lee: None declared, Lin Shi: None declared, Junbin Huang: None declared, Yan Kitty Kwok: None declared, Isaac C Yim: None declared, Tena K. Li: None declared, Vincent Lo: None declared, Jolly M Lee: None declared, Jack Jock Wai Lee: None declared, Ling Qin: None declared, Lai-Shan Tam Grant/research support from: Grants from Novartis and Pfizer

The automated sorting warehouses are operated by multiple AGVs simultaneously, which can quickly sort a large number of packages. How to solve the problems of multi-AGVs scheduling, path planning and conflict resolution is the key to the reliable and rapid operation of the warehouse system. In order to improve the reliability and sorting efficiency of the system, the objective of this paper is to minimize the maximum handling completion time. Firstly, a multi-AGVs path planning algorithm based on Grid Blocking Degree (GBD) is proposed. This algorithm can plan a conflict-free handling path for each handling task of each AGV, and update the path dynamically according to the real-time traffic congestion. Furthermore, aiming at the comprehensive optimization of scheduling and path planning, a scheduling algorithm based on priority rules is proposed to determine the handling task for AGVs. The data experiments compare the difference of the solution effect of different priority rules, and verify the effectiveness of the algorithm proposed in this paper.

Background: Bone erosion is a key feature of RA reflecting both disease severity and progression. HR-pQCT is an in-vivo clinical imaging system allowing detailed analysis of bone structure, including bone erosion. Several circulating microRNAs have already been suggested as potential biomarkers in RA. Objectives: To determine whether plasma cell-free circulating miRNAs are 1) associated with bone erosion at presentation and 2) predictive of erosion progression at 12 months as determined by HR-pQCT in patients with early rheumatoid arthritis (ERA). Methods: In this prospective study, 124 ERA patients were treated with a tight control protocol aiming at remission by using conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs). The second metacarpophalangeal joint (MCP2) was assessed for erosions by HR-pQCT at baseline and after 12 months. Plasma cell-free circulating miRNAs at baseline were identified by microRNA array in 10 treatment-naive ERA patients with maximal erosion volume at MCP2; in 10 treatment-naive ERA patients without erosion; and in 6 age- and sex-matched healthy controls. The 4 most dysregulated miRNAs were identified by TaqMan ® qRT-PCR in these same 20 ERA patients. Thereafter, the expression of these 4 selected miRNAs was validated in all 124 ERA patients at baseline. Results Of the 377 screened miRNAs, 155 miRNAs were detectable. 94 (60.6%) of these detectable miRNAs were upregulated in ERA patient with erosions, with 13 (8.4%) upregulated more than twofold. 61 (39.4%) miRNAs were downregulated in ERA patients with erosions, with 6 (3.9%) downregulated more than twofold. A total of 16 miRNAs were differentially expressed ( P P P =0.028) (table 1). Conclusions: Increased level of cell-free circulating miR-99b-5p was associated with erosions at presentation in ERA patients and could predict erosion progression as assessed by HR-pQCT over a period of 12 months, indicating that it may well serve as a biomarker of poor response to csDMARDs. Whether early biologic DMARDs use in these miR-99b-5p positive patients could reduce or prevent progression of erosion will need to be addressed in future studies. Acknowledgements: This study was partly supported by the Health and Medical Research Fund (project no 10110071). Disclosure of Interest: None declared

Intramuscular fatty acid (FA) is related to meat qualities such as juiciness, tenderness, palatability, and shear force. PPARα plays an important role in lipid metabolism in the liver and skeletal muscle. This study investigated FA composition in yaks and cattle, in order to ascertain whether a correlation between PPARα signal pathway genes as candidate genes and meat FA composition in yaks and cattle exists. Statistical analyses revealed that levels of monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) in yaks were significantly higher than those in cattle (P < 0.01), whereas saturated fatty acid (SFA) levels were significantly lower than those in cattle (P < 0.05). The mRNA expression levels of FABP4 (P < 0.05), SCP2 (P < 0.05), and APOA1 (P < 0.01) in yaks were significantly lower than those in cattle. However, LPL expression in yaks was significantly higher than that in cattle (P < 0.05). In yaks, the expression levels of FABP3 (P < 0.05) and LPL (P < 0.01) were negatively correlated with MUFA, and those of FABP4 and SCD were positively correlated with PUFA (P < 0.01). In cattle, the mRNA level of PLTP was positively correlated with SFA (P < 0.05), and LPL was positively correlated with MUFA (P < 0.05). These results suggest that these genes may participate in the regulation and control of intramuscular FA metabolism in yaks, so they could be used as candidate markers to improve yak meat quality.

Low carbon city research has become a hot topic, and the research has presented a complex and scattered situation. However there is a lack of comprehensive review on the existing studies in this discipline field of research. The research data used in this paper are collated from the articles on the low carbon city in 198 journals which are Chinese core and the Chinese Social Sciences Citation Index (CSSCI) journals. The high frequency keywords (HFK) in there research articles are identified from these 198 journals. These HFKs are further examined by using. By using EXCEL software, the co-word matrix, similar matrix and dissimilarity matrix are built; Furthermore, by using SPSS software, HFKs are classified into 14 clusters of low carbon city in china. These clusters show the status of the existing studies on low carbon cities in china; By mapping the strategic coordinates, we know the location of different classes. The understanding on the research status of the discipline of low carbon city in China can provide valuable references to make both researchers and practitioners get a better grasp of low carbon city study status.

Aims To estimate recent secular changes in the incidence and prevalence of diabetes and pre-diabetes among Hong Kong Chinese adults, and thus show possible future trends for developing mainland China. Methods Based on a complete census of the public sector health records of 6.4 million people from 2006 to 2014, diabetes cases were ascertained using different methods including the World Health Organization (WHO) 2011 guidelines (HbA1c, fasting plasma glucose and glucose tolerance test), American Diabetes Association (ADA) 2015 guidelines (plus random plasma glucose), and additionally recorded diagnosis codes and medication dispensation. Pre-diabetes was defined using ADA 2015 guidelines. Results We identified 697 201 people with diabetes (54.2% were incident cases); and 1 229 731 people with diabetes or pre-diabetes. In 2014, the overall incidence of diabetes was 9.46 per 1000 person-years [95% confidence interval (CI): 9.38 to 9.54], and overall prevalence was 10.29% (95% CI: 10.27% to 10.32%). Incidence decreased significantly from 2007 to 2014 (quadratic trend, P

Background: Autism spectrum disorder (ASD) is a multifactorial disorder which causes communication, behavioral, as well as developmental impairments, and it significantly impacts the quality of life of both the patients and their families. While the exact cause of ASD still remains unclear, it is proposed to be a complex interaction between genetic and environmental factors, and the immune system plays a role in responding to such factors. The use of intravenous immunoglobulin (IVIG) has been shown to be effective in a number of immune disorders, however, its role in ASD management still remains undefined. Evidence shows that low immunoglobulin (Ig) level is related to increased ASD symptoms, but no studies have connected such relationship to any specific drug therapy to the best of our knowledge.Objectives: To evaluate the use of IVIG as a potential therapy for ASD symptoms management in patients who have coexisting immune system disorder, specifically in those with low IgG and IgM levels.Methods...

The aim was to evaluate the principal clinical and conventional radiological features of a consecutive series of cases of orthokeratinized odontogenic cyst (OOC) affecting a Hong Kong Chinese community and to determine the outcome by follow-up.All cases were accompanied by appropriate radiography and were confirmed by histopathology.The clinical and conventional radiological presentations, differential diagnoses and outcomes of follow-up of five consecutive OOCs were reviewed. There were two males and three females. All affected the posterior sextant. The mean age at first presentation was 33.5 years. The mean of their period of prior awareness was 0.11 years. Swelling was the most frequent presenting symptom. All presented as well-defined corticated radiolucencies; three were unilocular and two were multilocular and all displayed expansion. This resulted in displacement and erosion of the lower border of the mandible in one case and the downward displacement past the lower border of a lateral cortex in two others. The inferior dental canal in each mandibular case exhibited both displacement and absence. The antrum was affected in a sole maxillary case. Four patients were followed up for a mean of 8.5 years. The fifth patient discharged himself shortly after surgery. No lesions recurred.OOCs in this community displayed an expansile character, but did not recur after moderately long follow-up. The time between the prior awareness of their disease and their presentation for diagnosis and treatment was, so far, the shortest for any lesion affecting the jaw in this Hong Kong Chinese community.

To evaluate the principal clinical and radiological features of a consecutive series of cases of fibrous dysplasia (FD) affecting a Hong Kong Chinese community and to determine their outcome by follow-up.All cases were accompanied by appropriate radiography and were histopathologically confirmed as fibro-osseous lesions.The clinical and radiological presentations, differential diagnoses and outcomes of follow-up of 21 consecutive FD cases were reviewed. Females were slightly more frequently affected, but there was no gender predilection for either jaw. The mean age at first presentation was 25 years, which upon adjustment for prior awareness fell to 21 years. The main symptom was swelling (including enlargement of the jaw). The maxilla and mandible were affected in 9 and 13 cases, respectively; both jaws were affected in 1 case. One case was of McCune-Albright syndrome. The sole provisional diagnosis for all lesions was FD; most lesions affected all or almost half the affected jaw. 17 patients were followed-up for a mean of 9 years.This very detailed consecutive series followed up over many years, in which a number of cases recurred or were reactivated in adulthood, firmly dispells the notion that FD is a simple hamartoma in all cases. This community was quite amenable to really long-term follow-up.

The microstructures of YBa2Cu3O7-delta (YBCO) thin films deposited on Si(001) wafers with an yttrium-stabilized ZrO2 (YSZ) single buffer or/and an Eu2CuO4(ECO)/YSZ double buffer layer were investigated by using high-resolution x-ray diffraction, small angle reflection and scanning electron microscopy (SEM), respectively. The results showed that the YBCO films were well oriented in the [001] direction perpendicular to the substrate surface. A thin intermediate layer of BaZrO3 was observed at the interface of YBCO/YSZ for samples with a YSZ single buffer. The composition of the YBCO film was also diverse from the 1-2-3 compound. In contrast, a well-defined interface was formed for samples with an ECO/YSZ double buffer. The film surface was more smooth and stable. The composition of the YBCO films was also found to approach that of the 1-2-3 compound. The results obtained indicate that highly epitaxial YBCO thin films could be successfully grown on Si wafers with a double buffer of ECO/YSZ. demonstrating advantages of such a double buffer structure.

Background The premise of this study is that the increased familial risk for alcoholism is associated with genetic determinants of the response to alcohol, characterized by sensitivity and adaptation. Following a single administration, sensitivity is the initial response to alcohol, expressed as the change in dependent measures from baseline. Adaptation of dependent measures within a single exposure to alcohol can be expressed as acute tolerance (recovery of dependent measures toward baseline values) or sensitization (movement of dependent measure further away from baseline values). This study tested the hypothesis that family history-positive (FHP) subjects are more sensitive and more adaptive to alcohol compared with family history-negative (FHN) subjects. Methods The initial response and development of adaptation to alcohol were assessed by using self-reported subjective perceptions during a breath alcohol concentration (BrAC) clamp of 60 mg%. The Biphasic Alcohol Effects Scale, the Sensation Scale and a visual analog scale of intoxication were acquired at baseline, after the BrAC clamp was established, and after maintenance of the clamp for 105 min. Results FHP subjects were more sensitive to alcohol compared with FHNs, as evidenced by greater changes in feelings of intoxication when the BrAC clamp was initially achieved. While the clamp was maintained, the FHP subjects adapted to the effects of alcohol and their perceptions of intoxication became indistinguishable from those of the FHN subjects. The FHP subjects had developed acute tolerance to alcohol, whereas the FHN subjects did not. Other self-reported perceptions of alcohol's effects did not distinguish between the groups. Conclusions A differential family history of alcoholism was reflected in self-reported subjective perceptions of intoxication when the brain's exposure to a specified concentration of alcohol was held constant (BrAC of 60 mg%). FHP subjects reported greater intoxication after alcohol and subsequently developed acute tolerance to alcohol compared with FHN subjects.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Hiroshi Suwaki and Harold Kalant. The presentations were (1) Influence of ADH genotypes on acute alcohol withdrawal syndrome in Japanese, by Susumu Higuchi; (2) Use of genetic analyses to refine phenotypes related to alcohol tolerance and dependence, by John C. Crabbe; (3) Neurochemical basis for alcohol dependence, by Seitaro Ohkuma and Masashi Katsura; (4) Adenylyl cyclase and development of tolerance to addictive drugs, by Masami Yoshimura; (5) Tolerance in rat lines selectively bred for alcohol preference, by Robert C. Stewart and Ting-Kai Li; and (6) Ethanol reinforcement, dependence, and vulnerability to relapse: Interactions between neuroadaptive and conditioning factors, by Friedbert Weiss.

A two-arm spectrometer, designed to detect η and π 0 mesons, has been built and used in (π, η) measurements at LAMPE. This spectrometer contains BGO active converters and NaI total-energy counters. Its construction and performance for ( π − , π 0 ) and ( π − , η) measurements on CH 2 are described. Novel techniques to monitor the gains of the BGO an NaI counters are also presented.

Electric-current-dependent resistance has been studied in epitaxial thin films of La0.7Ca0.3MnO3 and La0.85Ba0.15MnO3. Attention was focused at the influence of the applied dc current on the resistance of these epitaxial thin films in the absence of a magnetic field. A significant change in the ratio of the peak resistance at different currents or current resistance was found to be ∼23%–26% with a current density up to 8×104 Acm−2. For both La0.7Ca0.3MnO3 and La0.85Ba0.15MnO3 compounds, the dependence of the measured resistance on the current revealed a good linear relationship. Although the nature behind such an effect has not been well understood yet, the feature that the resistance in doped manganese oxides could be easily controlled by the electric current should be of interest for various applications such as field effect devices.

PGE2 is an immunomodulator that selectively inhibits the production of lymphokines associated with Th1 cells (IL-2 and IFN-gamma) but not Th2 cells (IL-4 and IL-5). We examined the effect of PGE2 on the production of IL-3 and granulocyte-macrophage (GM)-CSF from murine Th1 and Th2 clones. When the T cells were stimulated with Ag and APC, PGE2 inhibited IL-3/GM-CSF production from 3 Th1 clones and 1 Th2 clone, but enhanced production from 3 Th2 clones. A more specific bioassay demonstrated that IL-3 production was differentially affected by PGE2 in the Th clones. These data suggested that the effect of PGE2 on IL-3 production is dependent, not on a property of the lymphokine, but on a property of the T cell. The responsiveness to PGE2 did not consistently differ between Th1 and Th2 cells, and the observed heterogeneity in the response of Th2 clones did not correlate with the ability to induce increases in intracellular [Ca2+]. However, we postulated that signaling differences between the clones might explain the varied responsiveness to PGE2. If so, then the mode of stimulation might be expected to activate different pathways and thus affect the PGE2-responsiveness. Stimulation with ionomycin induced variable levels of IL-3/GM-CSF from the T cell clones. APC-derived costimulation dramatically enhanced IL-3/GM-CSF; the cells which produced high levels in response to ionomycin alone were not detectably costimulating each other. Interestingly, PGE2 enhanced IL-3/GM-CSF (and IL-3 alone in at least some cases) from cells stimulated with ionomycin alone, demonstrating that the mode of stimulation affects the PGE2-responsiveness. Addition of APC not only enhanced lymphokine production, but also altered the PGE2-responsiveness of the Th1 cells. In these cells, PGE2 either inhibited IL-3 and GM-CSF production or had no effect, in no case was the lymphokine production enhanced by PGE2 as it had been with ionomycin alone. These data indicate that the presence of APC-derived costimulatory signals can alter the effect of PGE2 on Th cell lymphokine production.

High-Tc Josephson junctions with a graded barrier have been prepared by using a composite target. Such a barrier is synthesized by utilizing Y1−xPrxBa2Cu3Oy with a continually graded concentration of Pr, in which no lattice mismatch and other incompatible problems take place. The structural interfaces are absent in the weak link region and Josephson coupling occurs at the naturally formed superconducting/normal interfaces within the Y1−xPrxBa2Cu3Oy layer. Thus, it can significantly enhance the reproducibilty and performance of these junctions. The temperature dependences of the barrier thickness and Josephson were also studied.

The aim of this study was to evaluate the clinical and conventional radiological features of a consecutive series of cases of "keratocystic odontogenic tumour" (KCOT) affecting a Hong Kong Chinese community and to determine their outcome by follow-up.All cases were accompanied by appropriate radiography and were histopathologically confirmed.33 consecutive KCOTs were reviewed. 18 patients were male. The mean age at first presentation was 30.6 years. Swelling was the most frequent presenting symptom. Those patients first presenting with pain were significantly older, whereas those first presenting with a maxillary lesion were significantly younger. The maxilla and mandible were affected in 13 and 20 cases, respectively. KCOTs were most frequently confined to the posterior sextants of both jaws. KCOTs affecting the maxilla were mainly unilocular, whereas those affecting the mandible were multilocular. Patients with multilocular KCOTs were significantly older. Patients with KCOTs associated with root resorption were significantly older, whereas patients associated with unerupted teeth were significantly younger. 69% displaced teeth, 41% resorbed them and 56% were associated with unerupted teeth. All but two were followed up for at least 2 years. Three lesions recurred.KCOTs in this community displayed some differences from those reported in the literature.

The hippocampus is sensitive to the effects of ethanol and appears to have a role in the development of alcohol tolerance. The objective of this study was to test the hypothesis that there are innate differences in gene expression in the hippocampus of inbred alcohol-preferring (iP) and -nonpreferring (iNP) rats that may contribute to differences in sensitivity to ethanol and/or in the development of tolerance. Affymetrix microarrays were used to measure gene expression in the hippocampus of alcohol-naive male iP and iNP rats in two experiments (n=4 and 6 per strain in the two experiments). Combining data from the two experiments, there were 137 probesets representing 129 genes that significantly differed (Por = 0.01); 62 probesets differed at Por = 0.001. Among the 36% of the genes that were expressed more in the iP than iNP rat at this level of significance, many were involved in cell growth and adhesion, cellular stress reduction and anti-oxidation, protein trafficking, regulation of gene expression, synaptic function and metabolism. Among the 64% of the genes that had lower expression in the hippocampus of iP than iNP rats were genes involved in metabolic pathways, cellular signaling systems, protein trafficking, cell death and neurotransmission. Overall, the data indicate that there are significant innate differences in gene expression in the hippocampus between iP and iNP rats, some of which might contribute to the differences observed in the development of alcohol tolerance between the selectively bred P and NP lines.

Alcoholism is a disease that runs in families and results at least in part from genetic risk factors. The Collaborative Study on the Genetics of Alcoholism (COGA) is a Federally funded effort to identify and characterize those genetic factors. The study involves more than 1,000 alcoholic subjects and their families, with researchers conducting comprehensive psychological, physiological, electrophysiological, and genetic analyses of the participants. These analyses have identified several traits, or phenotypes, that appear to be genetically determined, such as the presence of alcohol dependence, the level of response to alcohol, the presence of coexisting depression, or the maximum number of drinks a person consumes per occasion. Genetic analyses have identified regions on several chromosomes that are associated with these phenotypes and need to be studied further.

Structure, transport properties, and electronic structure of epitaxial thin films ${\mathrm{La}}_{0.9}{\mathrm{Sn}}_{0.1}{\mathrm{MnO}}_{3}$ and ${\mathrm{La}}_{0.9}{\mathrm{Ca}}_{0.1}{\mathrm{MnO}}_{3}$ have been experimentally studied. According to the Hall-effect measurement, ${\mathrm{La}}_{0.9}{\mathrm{Sn}}_{0.1}{\mathrm{MnO}}_{3}$ is an n-type conductor in the metallic state due to the substitution of Sn for La. X-ray photoelectron spectroscopy spectra revealed a shift of the Fermi level and the Mn ionic core level of ${\mathrm{La}}_{0.9}{\mathrm{Sn}}_{0.1}{\mathrm{MnO}}_{3}$ in comparison with ${\mathrm{La}}_{0.9}{\mathrm{Ca}}_{0.1}{\mathrm{MnO}}_{3}.$ The difference between the $\mathrm{Mn}\ensuremath{-}2p$ spectra of ${\mathrm{La}}_{0.9}{\mathrm{Sn}}_{0.1}{\mathrm{MnO}}_{3}$ and ${\mathrm{La}}_{0.9}{\mathrm{Ca}}_{0.1}{\mathrm{MnO}}_{3}$ implies that Mn ions in the former are at a ${\mathrm{Mn}}^{2+}/{\mathrm{Mn}}^{3+}$ mixed-valence state, which is significantly different from the divalent-element-doped manganese oxides, where the Mn ions are in the mixed-valence state of ${\mathrm{Mn}}^{3+}/{\mathrm{Mn}}^{4+}.$

The premise of this study is that the increased familial risk for alcoholism is associated with genetic determinants of the response to alcohol, characterized by sensitivity and adaptation. Following a single administration, sensitivity is the initial response to alcohol, expressed as the change in dependent measures from baseline. Adaptation of dependent measures within a single exposure to alcohol can be expressed as acute tolerance (recovery of dependent measures toward baseline values) or sensitization (movement of dependent measure further away from baseline values). This study tested the hypothesis that family history-positive (FHP) subjects are more sensitive and more adaptive to alcohol compared with family history-negative (FHN) subjects.The initial response and development of adaptation to alcohol were assessed by using self-reported subjective perceptions during a breath alcohol concentration (BrAC) clamp of 60 mg%. The Biphasic Alcohol Effects Scale, the Sensation Scale and a visual analog scale of intoxication were acquired at baseline, after the BrAC clamp was established, and after maintenance of the clamp for 105 min.FHP subjects were more sensitive to alcohol compared with FHNs, as evidenced by greater changes in feelings of intoxication when the BrAC clamp was initially achieved. While the clamp was maintained, the FHP subjects adapted to the effects of alcohol and their perceptions of intoxication became indistinguishable from those of the FHN subjects. The FHP subjects had developed acute tolerance to alcohol, whereas the FHN subjects did not. Other self-reported perceptions of alcohol's effects did not distinguish between the groups.A differential family history of alcoholism was reflected in self-reported subjective perceptions of intoxication when the brain's exposure to a specified concentration of alcohol was held constant (BrAC of 60 mg%). FHP subjects reported greater intoxication after alcohol and subsequently developed acute tolerance to alcohol compared with FHN subjects.

The primary goal of this study was to evaluate how race and sex interact with the effects of a moderate dose of alcohol on different ocular control subsystems in African American (AA) and non-Hispanic white American (WA) college students.Horizontal visually guided (VG) saccades and antisaccades (AS) of 80 young adult, healthy, AA and WA college students were recorded with an infrared system. Subjects ingested 10 aliquots of ethanol at 3 min intervals, with the aggregate dose precalculated to yield a peak breath alcohol concentration (BrAC) of 80 mg%. Data from the measures performed at baseline and the ascending and descending limbs of the BrAC at approximately 65 mg% were compared across race and sex by multivariate analysis of variance. A no-alcohol control session, performed in 20 of the subjects, documented test-retest reliability of the VG and AS measurements.Both AA and WA groups demonstrated slowing of AS and VG saccades after alcohol administration, but there was no significant effect of 65 mg% alcohol on VG accuracy or AS errors. AS latency recovered toward baseline values, whereas the slowing of VG latency/velocity progressed, during alcohol exposure. There were significant differences between AA and WA groups in the time course of VG latency after alcohol but not in most other dependent measures. No significant effects for sex were observed in any of the saccade measures. The faster disappearance of alcohol in WA compared with AA was replicated, and some measures demonstrated a significant, albeit small, negative correlation between the alcohol disappearance rate and impairing effects of alcohol on saccades.Prolonged latencies and unchanged percentage of errors reflect a differential effect of alcohol on neural function in specific areas (parietal eye field, superior colliculus, and frontal eye areas). Race may interact with the effect of ethanol on saccadic eye movements in a college student population.

The inbred preferring (iP) and nonpreferring (iNP) rat strains were derived from the selectively bred alcohol-preferring (P) and alcohol-nonpreferring (NP) lines. Previously, 381 iP x iNP F2 progeny were generated to identify quantitative trait loci (QTLs) influencing alcohol consumption and preference. Saccharin consumption (ml/48 h) and saccharin intake (ml/kg/day) were also measured in the F2 sample and were significantly correlated with both alcohol consumption and preference (all ror = .20, p.0001), suggesting that there might be some QTLs influencing both saccharin and alcohol phenotypes. We have performed a genome screen using F2 animals with extreme saccharin or alcohol consumption to identify QTLs contributing to saccharin-related phenotypes. Lod scores greater than 2.0 were found on chromosomes 3, 16 and 18 in this sample. Additional genotyping was performed in these regions in the full sample of 381 F2 progeny to further characterize these putative QTLs. On chromosome 3, the maximum lod score in the full sample was 2.7 with saccharin consumption. This QTL appears to overlap with a QTL identified for alcohol consumption in the iP and iNP lines and has pleiotropic effects on both phenotypes. Interestingly, this region of rat chromosome 3 is syntenic with mouse chromosome 2, where a QTL influencing alcohol preference has been previously reported. The QTL on chromosome 16 has a maximum lod score of 4.0 with saccharin intake and 2.6 with saccharin consumption. The QTL on chromosome 18 has a maximum lod score of 2.7 with saccharin consumption. Taken together, these data provide the first results of a genome screen for QTLs contributing to saccharin phenotypes in the rat.

Fetal alcohol syndrome (FAS) is particularly common among the mixed-ancestry population of the Western Cape Province of South Africa and occurs at a frequency of 0.0392-0.0429 (39.2-42.9 of 1000) among 5- to 9-year-old school entrants. While FAS is clearly caused by an environmental insult, studies in twins and mice support a significant genetic contribution to risk for FAS. It is likely that the development of FAS following excessive alcohol exposure is influenced by genetic factors in both the mother and the child. Known polymorphisms of the alcohol dehydrogenase-2 (ADH2) gene resulting in isozymes with different alcohol oxidizing capacities were investigated as possible candidates for influencing the risk for FAS.Genotyping was undertaken for the ADH2 locus in 56 FAS-affected children, their 56 mothers, and 178 control individuals of mixed ancestry from the same geographic region. The ADH2 alleles were analyzed for the three groups and the allele frequencies of the mother and FAS-affected children were independently compared with the control group.The ADH2*2 allele was found to be significantly more common in the control group than in the mothers of FAS-affected children (p = 0.025 +/- 0.004) and in the FAS subjects (p = 0.025 +/- 0.004). The ADH2*3 allele frequency was low and was not significantly different between the groups.The ADH2*2 allele is significantly more common in control individuals, suggesting that it may either confer protection or be a marker for a protective effect against FAS among individuals of mixed ancestry in the Western Cape Province of South Africa.

A variety of genetically influenced alcohol-related phenotypes relate to risk for alcohol dependence. In Asians, variation in the alcohol dehydrogenase (ADH2) gene relates to alcohol dependence, alcohol consumption, and reported alcohol-related symptoms, even after controlling for variation in the aldehyde dehydrogenase (ALDH2) gene. The association of ADH2 polymorphisms with alcohol-related behavior, however, has not been well characterized in non-Asians. This study evaluated 84 Ashkenazic Jewish American college students to determine the prevalence of the ADH2*2 allele (0.31). Carriers of ADH2*2 reported significantly fewer drinking days per month. ADH2*2, however, was not related to alcohol use disorders, alcohol-induced flushing and associated symptoms, number of binge drinking episodes in the past 90 days, maximum number of drinks ever consumed, or self-reported levels of response to alcohol. Results suggest that Ashkenazic Jewish Americans with ADH2*2 alleles drink less frequently, which might contribute, in part, to the overall lower rates of alcoholism in this population.

Camptothecin (CPT) induces down-regulation of topoisomerase I (TOP1) via an ubiquitin/26S proteasome pathway. Studies using a panel of breast and colorectal cancer cell lines as well as primary nontransformed and oncogene-transformed cells have demonstrated that CPT-induced down-regulation exhibits a high degree of heterogeneity. In general, nontransformed cells are much more proficient in CPT-induced TOP1 down-regulation than their transformed counterparts. Among the breast and colorectal cancer cell lines, there was a general correlation between the extent of CPT-induced TOP1 down-regulation and CPT resistance. The breast cancer cell line ZR-75-1, the most sensitive to CPT, was completely defective in CPT-induced TOP1 down-regulation, whereas the breast cancer cell line BT474, the least sensitive to CPT, exhibited effective CPT-induced TOP1 down-regulation. The 26S proteasome inhibitor MG132 was shown to inhibit CPT-induced down-regulation of TOP1 in BT474 cells and selectively sensitized BT474 but not ZR-75-1 cells to CPT-induced cytotoxicity and apoptosis. In the aggregate, these results suggest that CPT-induced down-regulation of TOP1 could be an important parameter for determining CPT sensitivity/resistance in tumor cells. Analysis of the levels of TOP1 cleavable complexes, SUMO-1-TOP1 conjugates, and ubiquitin-TOP1 conjugates in ZR-75-1 and BT474 cells has suggested that the heterogeneity of CPT-induced down-regulation of TOP1 in tumor cells is at least in part attributable to altered regulation of a process(es) downstream from the TOP1 cleavable complex.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chair was Edward P. Riley. The presentations were (1) Does alcohol withdrawal contribute to fetal alcohol effects? by Jennifer D. Thomas and Edward P. Riley; (2) Brain damage and neuroplasticity in an animal model of binge alcohol exposure during the "third trimester equivalent," by Charles R. Goodlett, Anna Y. Klintsova, and William T. Greenough; (3) Ganglioside GM1 reduces fetal alcohol effects, by Basalingappa L. Hungund; and (4) Fetal alcohol exposure alters the wiring of serotonin system at mid-gestation, by F. Zhou, Y. Sari, Charles Goodlett, T. Powrozek, and Ting-Kai Li.

This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Kenneth R. Warren and Faye J. Calhoun. The presentations were (1) Epidemiological research on fetal alcohol syndrome (FAS) in the United States, by Philip A. May; (2) An overview of fetal alcohol syndrome in the Western Cape Province of South Africa, by Denis L. Viljoen and Ting-Kai Li; (3) Diagnostic perspectives of fetal alcohol and tobacco syndromes, by Harumi Tanaka; (4) FAS among pupils of special boarding schools and orphanages in Moscow, Russia, by Galina S. Marinicheva and Luther K. Robinson; and (5) Research on FAS and FAE in Germany: Update and perspectives, by Goetz Mundle.

Research comparing the alcohol-preferring (P) and -nonpreferring (NP) rat lines has detected an apparent association between ethanol preference and lower responsivity to ethanol, as well as the capacity to develop and maintain tolerance to ethanol's effects. However, past studies of tolerance to ethanol's effects generally involved relatively high doses. The present study examined recovery from functional impairment induced by moderate doses of ethanol after a single dose (responsivity) and after multiple doses (development of tolerance) in the P and NP rat lines.Adult female P and NP rats were trained, for 5 consecutive days, to stay on an oscillating bar for 120 sec. Rats were then assigned to one of three groups to receive 1.0, 1.25, or 1.5 g/kg ethanol for 5 consecutive test days. Rats were tested each day at 15-min intervals, following intraperitoneal injection, until recovery to the 120 sec criterion.On the first test day, NP rats took longer to recover to criterion than the P rats following the 1.0 and 1.25 g/kg doses, whereas at the 1.5 g/kg dose no line difference was evident. Trunk blood alcohol concentrations (BACs), associated with time to recovery, indicated higher values for the P than NP rat on day 1 following injection of the two lower doses. Compared to day 1, NP rats demonstrated significantly shorter times to recovery beginning on day 2 following injections of the 1.0 and 1.25 g/kg doses. However, NP rats did not show significantly different recovery times on days 2-5 compared to day 1 following injection of the 1.5 g/kg dose. The shorter recovery times at the 1.0 and 1.25 g/kg doses were associated with BACs at recovery on day 3 being equal to or greater than values obtained on day 1. In contrast, compared to day 1, P rats did not show shorter recovery times until days 3 and 5 following the 1.0 and 1.25 g/kg doses, respectively. However, P rats did demonstrate shorter recovery times on day 2 and higher BACs on day 3 compared to day 1 following the 1.5 g/kg dose.With regard to motor impairment, lower responsivity to moderate doses of ethanol may be a factor associated with high alcohol-seeking behavior. The present results confirm past research supporting an association between ethanol preference and low ethanol responsivity but at doses that are more reflective of those self-administered by P rats.