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The incidence of second stage cesarean delivery has been rising globally because of the failure or the anticipated difficulty of performing instrumental delivery. Yet, the best way to interpret the figure and its optimal rate remain to be determined. This is because it is strongly influenced by the practice of other 2 modes of birth, namely cesarean delivery performed before reaching the second stage and assisted vaginal birth during the second stage. In this regard, a bubble chart that can display 3-dimensional data through its x-axis, y-axis, and the size of each plot (presented as a bubble) may be a suitable method to evaluate the relationship between the rates of these 3 modes of births. This study aimed to conduct an epidemiologic study on the incidence of second stage cesarean deliveries rates among >300,000 singleton term births in 10 years from 8 obstetrical units and to compare their second stage cesarean delivery rates in relation to their pre-second stage cesarean delivery rates and assisted vaginal birth rates using a bubble chart. The territory-wide birth data collected between 2009 and 2018 from all 8 public obstetrical units (labelled as A to H) were reviewed. The inclusion criteria were all singleton pregnancies with cephalic presentation that were delivered at term (≥37 weeks' gestation). Pre-second stage cesarean delivery rate was defined as all elective cesarean deliveries and those emergency cesarean deliveries that occurred before full cervical dilatation was achieved as a proportion of the total number of births. The second stage cesarean delivery rate and assisted vaginal birth rate were calculated according to the respective mode of delivery as a proportion of the number of cases that reached full cervical dilatation. The rates of these 3 modes of births were compared among the parity groups and among the 8 units. Using a bubble chart, each unit's second stage cesarean delivery rate (y-axis) was plotted against its pre-second stage cesarean delivery rate (x-axis) as a bubble. Each unit's second stage cesarean delivery to assisted vaginal birth ratio was represented by the size of the bubble. During the study period, a total of 353,434 singleton cephalic presenting term pregnancies were delivered in the 8 units, and 180,496 (51.1%) were from nulliparous mothers. When compared with the multiparous group, the nulliparous group had a significantly lower pre-second stage cesarean delivery rate (18.58% vs 21.26%; P <.001) but a higher second stage cesarean delivery rate (0.79% vs 0.22%; P <.001) and a higher assisted vaginal birth rate (17.61% vs 3.58%; P <.001). Using the bubble of their averages as a reference point in the bubble chart, the 8 units' bubbles were clustered into 5 regions indicating their differences in practice: unit B and unit H were close to the average in the center. Unit A and unit F were at the upper right corner with a higher pre-second stage cesarean delivery rate and second stage cesarean delivery rate. Unit D and unit E were at the opposite end. Unit C was at the upper left corner with a low pre-second stage cesarean delivery rate but a high second stage cesarean delivery rate, whereas unit G was at the opposite end. Unit C and unit G were also in the extremes in terms of pre-second stage cesarean delivery to assisted vaginal birth ratio (0.09 and 0.01, respectively). Although some units seemed to have very similar second stage cesarean delivery rates, their obstetrical practices were differentiated by the bubble chart. The second stage cesarean delivery rate must be evaluated in the context of the rates of pre-second stage cesarean delivery and assisted vaginal birth. A bubble chart is a useful method for analyzing the relationship among these 3 variables to differentiate the obstetrical practice between different units. [Display omitted] [ABSTRACT FROM AUTHOR]

• Prevalence rate of proteinuria was 17.7%. • Prevalence rate of chronic metabolic acidosis was 6.2%. • High protein intake is a risk factor of proteinuria among kidney transplant recipients. • Dietary acid load did and dietary salt not correlate with both proteinuria and metabolic acidosis. Proteinuria and metabolic acidosis adversely affect long term renal allograft outcome and are highly prevalent in reported studies. The role of dietary intake in influencing proteinuria and metabolic acidosis remained uncertain. This study aims to determine the prevalence rate of proteinuria and metabolic acidosis among kidney transplant recipients (KTRs) and to study their relationship with dietary intake. We performed a cross-sectional study on KTRs with functioning renal allograft and at least 3 months post transplant. Dietary protein, salt, and dietary acid load were estimated using 24-hour urine collection. Demographic characteristics, concomitant medications, medical history, and laboratory results were obtained from electronic medical records. A total of 204 KTRs were recruited with median age of 48 years (interquartile range [IQR], 18 years); male to female ratio was 61:39. A total of 79.9% (n = 163) were living related kidney transplants. The median duration after transplant was 71 months (IQR, 131 months), and median eGFR was 65 mL/min/1.73 m2 (IQR, 25 mL/min/1.73 m2). The prevalence rates of proteinuria (defined as ≥ 0.5 g/d) and metabolic acidosis (defined as at least 2 readings of serum bicarbonate ≤ 22 mmol/L in the past 6 months) were 17.7 % and 6.2%, respectively. High dietary protein of > 1.2 g/kg ideal body weight (adjusted odds ratio, 3.13; 95% CI, 1.35-7.28; P =.008) was significantly associated with proteinuria. Dietary protein, salt, and acid load did not correlate with chronic metabolic acidosis. The prevalence rate of proteinuria is consistent with published literature, but metabolic acidosis rate is extremely low in our cohort. High protein intake (> 1.2 g/kg ideal body weight) is a risk factor of proteinuria and may have negative impact on KTR outcome. [ABSTRACT FROM AUTHOR]

• Novel MALDI-MSI performed to visualise spatial distribution of oat lipids. • Detection of oat triacylglycerols enhanced via sodium doping. • TIMS activation improved signal intensities and lipid identification. • Isobaric lipids with distinct localisation patterns were identified in oats. • Findings may support further explorations into physiological roles of lipids in oats. Oat (Avena sativa L.) is an important cereal grain with a unique nutritional profile including a high proportion of lipids. Understanding lipid composition and distribution in oats is valuable for plant, food and nutritional research, and can be achieved using MALDI mass spectrometry imaging (MALDI-MSI). However, this approach presents several challenges for sample preparation (hardness of grains) and analysis (isobaric and isomeric properties of lipids). Here, oat sections were successfully mounted onto gelatin-coated indium tin oxide slides with minimal tearing. Poor detection of triacylglycerols was resolved by applying sodium chloride during mounting, increasing signal intensity. In combination with trapped ion mobility spectrometry (TIMS), lipid identification significantly improved, and we report the separation of several isobaric and isomeric lipids with visualisation of their "true" spatial distributions. This study describes a novel MALDI-TIMS-MSI analytical technique for oat lipids, which may be used to improve the discovery of biomarkers for grain quality. [ABSTRACT FROM AUTHOR]

The USEPA and the WHO now advocate the use of enterococci as indicators for marine water quality. This study investigated the outcomes for Hong Kong beach water quality assessment by comparing enterococcus measures with data from the HKEPD's monitoring programme. Six beaches were tested once every 2–3 months from November 2013 to June 2014 in order to identify the most contaminated sites, followed by intensive water sampling in sites found to have the highest enterococci densities (Clear Water Bay Second and Golden) every five to six days for six sampling events over a 30-day period in 2014. The geometric means of enterococci were found to be 124 and 41 cfu/100 mL at Clear Water Bay Second and Golden respectively, indicating that there may be higher risks of illness associated with swimming at both beaches than previously known. Moreover, beach sediments contained higher concentrations of enterococci than water, and warrant further study. [ABSTRACT FROM AUTHOR]

Summary Background & aims Patients undergoing gastrointestinal operations are at risk of malnutrition which may increase the chance of adverse surgical outcomes. This prospective study aimed at correlating nutritional status of patients having gastrointestinal operations with their short-term surgical outcomes captured by a territory-wide Surgical Outcomes Monitoring and Improvement Program. Methods The preoperative malnutrition risk of Chinese adult patients undergoing elective/emergency ultra-major/major gastrointestinal operations in two surgical departments over a 12-month period were assessed by Chinese version of Malnutrition Universal Screening Tool. Their perioperative risk factors and clinical outcomes, including length of hospital stay, mortality and morbidity, were retrieved from the above mentioned program. Correlation of malnutrition risk with clinical outcomes was assessed by logistic regression analysis after controlling for known confounders. Results 943 patients (58% male; mean age 65.9 ± 14.8 years) underwent gastrointestinal operations (40.3% emergency operation; 52.7% ultra-major procedures; 66.9% bowel resections) had analyzable data. 15.8% and 17.1% of patients were at medium and high risk of malnutrition, respectively. Malnutrition risk score according to the screening tool was an independent predictor of length of hospital stay, 30-day mortality, 60-day mortality and minor medical complications. Similar correlations were found for various sub-scores of malnutrition risk. Weight loss sub-score was predictive of 30-day mortality, 60-day mortality and minor medical complications. Body mass index was predictive of mortality (30- and 60- day) whereas the acute disease sub-score was predictive of length of hospital stay. Conclusions Preoperative malnutrition was an important predictor of poor clinical outcomes in patients undergoing gastrointestinal operations in Hong Kong. [ABSTRACT FROM AUTHOR]

Abstract: This study evaluated the psychometric properties of a widely used self-report anxiety scale—the Spence Children''s Anxiety Scale (SCAS) and the associated parent-report version (PSCAS)—in a Hong Kong Chinese community sample. While good psychometric properties of SCAS and PSCAS had been documented in Western cultural contexts (e.g., Australia), no systematic psychometric evaluation of the Chinese-translated SCAS and PSCAS has been published. In this study, psychometric properties of SCAS and PSCAS were examined with respect to four criteria: (a) factor structure, (b) descriptive statistics, (c) convergent validity with an anxiety cognition measure, and (d) internal consistency. Psychometric properties of SCAS and PSCAS for a Chinese community sample were found to be highly comparable with those published on Australian samples, thus providing a solid conceptual foundation for use of the Chinese version of SCAS and PSCAS. [Copyright &y& Elsevier]

Abstract: This study evaluated the effectiveness of cognitive-behavioral treatment for childhood anxiety in a community clinic setting in Hong Kong, China. Forty-five clinically-referred children (age 6–11 years) were randomly assigned to either a cognitive-behavioral treatment program or a waitlist-control condition. Children in the treatment condition showed significant reduction in anxiety symptoms—both statistically and clinically—whereas children in the waitlist condition did not. After the waitlist period was over, the control group also received the treatment program and showed a similar reduction in symptoms. For the full sample of 45 children, the effectiveness of the intervention was significant immediately after treatment and in 3- and 6-month follow-ups. In addition, children’s anxiety cognition and their ability to cope with anxiety-provoking situations fully mediated the treatment gains. These results offer empirical support for cognitive-behavioral treatment programs in a non-Western cultural context and plausible mediators for how cognitive-behavioral therapy works. [ABSTRACT FROM AUTHOR]

Abstract: Ginsenoside Rg1, an active ingredient commonly found in ginseng root, was previously demonstrated to be a phytoestrogen that exerted estrogen-like activity without direct interaction with estrogen receptors (ERs) in human breast cancer (MCF-7) cells. The present study was designed to determine the molecular mechanism by which Rg1 exerted estrogenic effects. Co-incubation of MCF-7 cells with 1μM of ER antagonist ICI182780 abolished the inductive effects of Rg1 on pS2 expression as well as ERE-luciferase activity, suggesting that the estrogenic effects of Rg1 were mediated through the endogenous ERs. To evaluate the relative involvement of ERα and ERβ in mediating the actions of Rg1, ER-negative human embryonic kidney (HEK293) cells were co-transfected with the ERE-luciferase reporter construct and either ERα or ERβ construct. The results showed that Rg1 could activate ERE-luciferase activity via the ERα-mediated pathway in a dose-dependent manner (10−14 to 10−6 M); whereas, the activation of ERβ-mediated ERE-luciferase activity by Rg1 only occur at high concentration (10−6 M). Furthermore, the results showed that 1pM Rg1 could rapidly induce phosphorylation of the AF-1 domain of ERα at serine 118 residue within the first 5 min of incubation, suggesting that Rg1 activates ERα in a ligand-independent manner. Taken together, our results indicate that Rg1 preferentially activates ERα via phosphorylation of AF-1 domain in the absence of receptor binding. This study is the first to provide evidence that ginsenoside Rg1 exerts estrogen-like actions via ligand-independent activation of ERα pathway. [Copyright &y& Elsevier]

Abstract: A very thin dielectric flash layer (DFL) was used in addition to Ta for Cu/ultra-low-K (porous SiLK™) back-end technology. Atomic force microscopy showed that SiC DFL is superior to Si3N4 or SiO2 DFL in terms of smaller surface roughness. It appears to the authors that the key point to get a very smooth DFL is to avoid the use of nitrogen-containing gases like NH3, N2 or N2O during the DFL deposition process. An alternative explanation is that trimethylsilane is the better Si source compared to silane. Electrical testing showed that SiC DFL is superior to Si3N4 or SiO2 DFL in terms of higher breakdown voltage. [Copyright &y& Elsevier]

Creatinine clearance (CrCl) is more accurate than other methods when assessing renal allograft function, but it is inconvenient for patients. In clinical practice, renal allograft function is often estimated using estimated glomerular filtration rate (GFR) equations. This cross-sectional study compared agreement between CrCl and serum creatinine–based equations among renal transplant recipients (RTRs) attending a transplant clinic in a tertiary center. Six equations (Cockcroft-Gault, Walser's, Nankivell, abbreviated Modification of Diet in Renal Disease [MDRD], Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI], and European Kidney Function Consortium[EKFC]) were included in the analysis. The bias, precision, and accuracy of each equation were determined. Correlation analysis was performed by determining the correlation coefficient and plotting Bland-Altmann plots. A total of 165 subjects were included in this study. Mean serum creatinine was 112.03 ± 38.67 µmol/L, and mean CrCl was 58.44 ± 21.24 mL/min/1.73 m2. Walser's equation showed strongest correlation, lowest bias, and highest accuracy of the proportion of estimated GFR falling within ±30% of CrCl, followed by the 4-variable MDRD equation. All 6 equations systematically underestimated GFR among RTRs. Walser's equation showed the best estimation of GFR, suggesting that it may be the formula of choice to estimate GFR among RTRs. [ABSTRACT FROM AUTHOR]

Acquired hemophilia A (AHA) is a rare bleeding disorder with destruction of factor VIII by autoantibodies. Comprehensive data for Chinese patients are lacking. Predictors of hospital stay have not been investigated. A territory-wide review of patients diagnosed with AHA from January 1, 2012, to December 31, 2021 was performed by retrieving patients' information from an electronic database system in Hong Kong. Overall, 165 patients were included in this 10-year study, and the estimated incidence was 2.4 per million/year, which was higher than those reported from Caucasian cohorts. The median age of diagnosis was 80 years old. Patients had a long hospital stay (median: 25 days) and high mortality (55.2 %). The majority of deaths were caused by immunosuppression-related sepsis (49.5 %). Age was an independent predictor of overall survival (Hazard ratio: 1.065, 95 % CI: 1.037–1.093, p < 0.001), complete remission (CR) status (odd ratios (OR): 0.948, 95 % CI: 0.921–0.976, p < 0.001) and time to achieve CR (OR: 1.043, 95 % CI: 1.019–1.067, p < 0.001). Higher hemoglobin level on presentation was associated with shorter time to achieve CR (OR: 0.888, 95 % CI: 0.795–0.993, p = 0.037). Factor VIII level < 1 % normal, high inhibitor titer and intensive immunosuppressive regimen predicted long hospital stay. We presented comprehensive data of Chinese patients with AHA which comprised predominantly frail elderly who required long hospital stay and had high sepsis-related mortality. This posed challenges in managing AHA in such patients. Individualized immunosuppressive therapy is needed to balance the benefits and risk of septic complications. • A comprehensive review of AHA patients in Hong Kong which represented the disease characteristics of Chinese patients. • High mortality rate (55.2%) was recorded in our cohort and majority of death were sepsis relating to immunosuppression. • Age was an independent predictor of overall survival, CR status and time to achieve CR. • Factor VIII level <1% normal, high inhibitor titre and intensive immunosuppression were predictors of long hospital stay. [ABSTRACT FROM AUTHOR]

Abstract: The synthesis and γ-secretase inhibition data for a series of carbamate-appended N-alkylsulfonamides are described. Carbamate 54 was found to significantly reduce brain Aβ in transgenic mice. 54 was also found to possess markedly improved brain levels in transgenic mice compared to previously disclosed 1 and 2. [Copyright &y& Elsevier]

Abstract: A series of N-protected amino acid-estradiol derivative conjugates have been synthesized by coupling of 17β-aminoestra-1,3,5 (10)-trien-3-ol ( 1 ) or 17β-hydrazonoestra-1,3,5 (10)-trien-3-ol ( 2 ) with different amino acids via the catalysis of subtilisin Carlsberg in organic solvent. Various factors, including the structure of amino acid residue, different N-protecting groups of amino acids, different esters of carboxyl group and water content of the reaction media that influence the efficiency of enzymatic reactions were systematically studied. In vitro biological activity studies revealed that the binding interactions between estradiol derivative conjugates and estrogen receptor can be affected by the properties of the conjugated amino acid, but the effects of the change in binding properties did not result in changes in biological activities in both MCF-7 and HeLa cell lines. [Copyright &y& Elsevier]

Purpose: To determine the clinical outcome, prognostic factors, and effect of adding combination chemotherapy to radiation therapy on disease control and survival in early stage nasal natural killer (NK)/T-cell lymphoma.Methods and Materials: A retrospective “intent to treat” analysis was carried out on 79 patients treated consecutively with curative intent between 1977 and June 2001. They all had early stage (Ann Arbor Stage IE: 63, IIE:16) nasal NK/T-cell lymphoma. Sixty-one were planned for combined modality treatment (CMT); radiotherapy alone (RT) was intended for 18. Three to 6 cycles of anthracycline-containing regimens were aimed at for patients intended for CMT. Patients selected for RT were generally older or treated during the earlier part of the study period.Results: The overall complete response (CR) rate was 68.4% (54/79), of whom 44.4% (24/54) relapsed after 54.9 months median follow-up of the survivors. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 35.5% and 37.9%, respectively. On multivariate analysis, good performance status (Eastern Cooperative Oncology Group [ECOG] <2) was shown to be a significant favorable factor for DFS (p = 0.011), whereas good performance status (ECOG <2) and Ann Arbor Stage IE disease were shown to be significant favorable factors for OS (p = 0.001 and p = 0.013, respectively). The type of intended treatment was not a significant factor for DFS (5-year DFS CMT vs. RT = 35.8% vs. 30.5%, p = 0.795) or OS (5-year OS CMT vs. RT = 40.3% vs. 29.8%, p = 0.693) though only 2 of the 16 Stage IIE patients were intended for RT alone. Resistance to treatment, especially to chemotherapy, was common. Of 61 patients intended to be given CMT, 31 showed disease progression while receiving chemotherapy, of whom 17 progressed locoregionally. Nine of the latter group were rendered CR by salvage radiotherapy.Conclusions: The overall outcome in early stage nasal NK/T-cell lymphoma is poor. Performance status and Ann Arbor stage are significant factors influencing DFS and OS. The addition of anthracycline-containing chemotherapy to radiotherapy does not appear to confer any survival benefit in Stage IE patients. Therefore, radiation therapy remains the mainstay of treatment for this lymphoma type. [Copyright &y& Elsevier]

This paper reports the results of a comprehensive study conducted on the effect of surface morphology of titanium nitride (TiN) electrodes deposited by magnetron sputtering and the possibility of improving metal/insulator/metal (MIM) capacitor characteristics with Al 2 O 3 dielectric obtained by atomic layer deposition (ALD). From the atomic force microscopy (AFM) study, we found that the bottom TiN layer is rougher for thicker films. Post metallization annealing can slightly reduce the roughness. In the case of the Al 2 O 3 dielectric layer deposition, low-temperature ALD is preferred in order to obtain smaller surface roughness. Deposition of a dielectric layer at higher temperatures results in rougher surface because of poor chemisorption of precursors on the rough surface and the forming of crystalline phases. Electrical measurements show that the barrier at the top electrode is much larger than that at the bottom electrode due to the smaller roughness of the Al 2 O 3 surface. Trade-off is required for depositions of both the bottom electrode and the dielectric layer. [ABSTRACT FROM AUTHOR]

Shrinkages of cementitious materials may lead to cracking under restrained conditions. This study was motivated to develop non-shrinkage quaternary blended cements through blending slag and fly ash with Portland cement containing reactive MgO. The hydration process, autogenous shrinkage at early age, long-term volume deformation, mechanical properties, and microstructure of cement specimens were investigated. Results showed that the autogenous shrinkage of the cement pastes was effectively mitigated due to the compensation of the MgO present and the reduction of cement content owing to the partial replacements with slag and fly ash. The mechanical strengths of the blended cement mortars were lower than that of the corresponding plain Portland cement mortars at early age of 3 d, but increased significantly to be similar or higher at late ages of 28 d and 90 d. This is attributed to the microstructure densification and the interface microstructure enhancement due to the reaction of SCMs with clinker phases. [ABSTRACT FROM AUTHOR]

Background End-stage renal failure patients often fail to attend scheduled renal palliative care clinic (RPCC) follow-up because of acute hospital admissions, causing negative impact on patients' well-being and health care burden. Measures The rates of RPCC attendance, emergency department (ED) attendance, and acute hospital admission per patient from January 2013 to June 2013 were analyzed. Intervention Patients who had more than one ED visit within three months were invited to intensify their RPCC follow-up schedule for symptom assessment, medical advice, psychosocial-spiritual care, and social worker support in the subsequent three months. Outcomes Nineteen patients were included. The rate of ED attendance (2.63 vs. 0.63, P < 0.007) and acute hospital admission (1.59 vs. 0.58, P < 0.009) was reduced significantly after intensified follow-up. Clinic attendance rates improved from 56% to 85%. Conclusions/Lessons Learned Our pilot results suggested that intensifying RPCC follow-up minimized the utilization of acute medical services and improved outpatient attendance at RPCC. [ABSTRACT FROM AUTHOR]

Objective: Detailed description and follow-up of a patient with atypical polypoid adenomyoma and infertility, from investigation until delivery of a healthy baby. Design: Case report. Setting: Tertiary infertility center. Patient(s): A patient suffering from persistent APA and infertility. Intervention(s): Danggui (Angelica sinensis) and low-dose aspirin. Main Outcome Measure(s): Pregnancy and live birth. Result(s): Conception after Danggui but intrauterine death at 25 weeks. Successful live birth after Danggui plus low-dose aspirin. Conclusion(s): Danggui corrected atypical polypoid adenomyoma and led to pregnancy twice in the same patient. Low-dose aspirin may improve the circulation in the placental bed and lead to live birth. [Copyright &y& Elsevier]

Abstract: Background and purpose: To evaluate the therapeutic benefits by adding chemotherapy (+C) and/or accelerated-fractionation (AF) for patients with T3-4N0-1M0 nasopharyngeal carcinoma. Materials and methods: From 1999 to 2004, 189 eligible patients were randomized to one of four treatment groups (CF/CF+C/AF/AF+C). The number of fractions/week was 5 for the CF groups and 6 for the AF groups. Patients in the +C groups were given concurrent cisplatin plus adjuvant cisplatin and fluorouracil. Results: The AF+C group achieved significantly higher failure-free rate (88% at 5-year) than the CF group (63%; p =0.013), the AF group (56%; p =0.001) and the CF+C group (65%; p =0.027). As compared with CF alone, the increase in late toxicity was statistically insignificant (36% vs. 20%; p =0.25). Deaths due to cancer progression decreased (7% vs. 33%; p =0.011) but deaths due to incidental causes increased (9% vs. 2%; p =0.62). Improvement in overall survival reached borderline significance (85% vs. 66%; p =0.058). Conclusions: Concurrent-adjuvant chemotherapy combined with AF significantly reduced failure and cancer-specific deaths. Although the increase in major late toxicity and incidental deaths were statistically insignificant, a subtle increase in non-cancer deaths narrowed the overall survival gain. [ABSTRACT FROM AUTHOR]

Abstract: A series of N-alkylbenzenesulfonamides were developed from a high throughput screening hit. Classic and parallel synthesis strategies were employed to produce compounds with good in vitro and in vivo γ-secretase activity. [Copyright &y& Elsevier]

Purpose: To compare the benefit achieved by concurrent chemoradiotherapy (CRT) and/or accelerated fractionation (AF) vs. radiotherapy (RT) alone with conventional fractionation (CF) for patients with T3-4N0-1M0 nasopharyngeal carcinoma (NPC). Methods and Materials: All patients were irradiated with the same RT technique to ≥66 Gy at 2 Gy per fraction, conventional five fractions/week in the CF and CF+C (chemotherapy) arms, and accelerated six fractions/week in the AF and AF+C arms. The CF+C and AF+C patients were given the Intergroup 0099 regimen (concurrent cisplatin plus adjuvant cisplatin and 5-fluorouracil). Results: Between 1999 and April 2004, 189 patients were randomly assigned; the trial was terminated early because of slow accrual. The median follow-up was 2.9 years. When compared with the CF arm, significant improvement in failure-free survival (FFS) was achieved by the AF+C arm (94% vs. 70% at 3 years, p = 0.008), but both the AF arm and the CF+C arm were insignificant (p ≥ 0.38). Multivariate analyses showed that CRT was a significant factor: hazard ratio (HR) = 0.52 (0.28–0.97), AF per se was insignificant: HR = 0.68 (0.37–1.25); the interaction of CRT by AF was strongly significant (p = 0.006). Both CRT arms had significant increase in acute toxicities (p < 0.005), and the AF+C arm also incurred borderline increase in late toxicities (34% vs. 14% at 3 years, p = 0.05). Conclusions: Preliminary results suggest that concurrent chemoradiotherapy with accelerated fractionation could significantly improve tumor control when compared with conventional RT alone; further confirmation of therapeutic ratio is warranted. [Copyright &y& Elsevier]

Abstract: Background and purpose: To define the dose–response relationship of nasopharyngeal carcinoma (NPC) above the conventional tumoricidal dose level of 66Gy when the basic radiotherapy (RT) course was given by the 2D Ho''s technique. Patients and methods: Data from all five regional cancer centers in Hong Kong were pooled for this retrospective study. All patients (n=2426) were treated with curative-intent RT with or without chemotherapy between 1996 and 2000 with the basic RT course using the Ho''s technique. The primary endpoint was local control. The prognostic significance of dose-escalation (‘boost’) after 66Gy, T-stage, N-stage, use of chemotherapy, sex and age (≤40 years vs >40 years) was studied. Both univariate and multivariate analyses were performed. Results: On multivariate analysis, T-stage (P< 0.01; hazard ratio [HR], 1.58) and optimal boost (P=0.01; HR, 0.34) were the only significant factors affecting local failure for the whole study population, and for the population of patients treated by radiotherapy alone, but not for patients who also received chemotherapy. The following were independent determinants of local failure for patient groups with different T-stages treated by radiotherapy alone: use of a boost in T1/T2a disease (P=0.01; HR, 0.33); use of a boost (P<0.01; HR, 0.60) and age (P=0.01; HR, 1.02) in T3/T4 tumors. Among patients with T2b tumors treated by radiotherapy alone and given a boost, the use of a 20Gy-boost gave a lower local failure rate than a 10Gy-boost. There was no apparent excess mortality attributed to RT complications. Conclusions: Within the context of a multi-center retrospective study, dose-escalation above 66Gy significantly improved local control for T1/T2a and T3/4 tumors when the primary RT course was based on the 2D Ho''s technique without additional chemotherapy. ‘Boosting’ in NPC warrants further investigation. Caution should be taken when boosting is considered because of possible increase in radiation toxicity. [Copyright &y& Elsevier]

Using a cell-based assay, we have identified optimal residues and key recognition elements necessary for inhibition of γ-secretase. An (S)-hydroxy group or 3,5-difluorophenylacetyl group at the amino terminus and N-methyltertiary amide moiety at the carboxy terminus provided potent γ-secretase inhibitors with an IC50 <10 nM. [Copyright &y& Elsevier]

Purpose: To assess the role of intracavitary mold brachytherapy in salvaging local failure of nasopharyngeal carcinoma (NPC).Methods and Materials: The outcomes of 118 consecutive NPC patients with local failure treated with mold brachytherapy between 1989 and 1996 were retrospectively reviewed. Eleven patients received additional external radiotherapy.Results: All molds were tailor-made, and the whole procedure was performed under local anesthesia. Pharyngeal recess dissection was routinely performed to allow direct contact of the radioactive source with the pharyngeal recess, a common site of local failure. Initially, the molds were preloaded with 192Ir wires, but since 1992, the sources have been manually afterloaded; the mold has also been redesigned for better conformity, ease of insertion, and radiation safety. Using brachytherapy alone, 50–55 Gy was given for recurrence in 4–7 days; for persistence, 40 Gy was administered. The overall complete remission rate was 97%. The rates of 5-year local control, relapse-free survival, disease-specific survival, overall survival, and major complication were 85%, 68.3%, 74.8%, 61.3%, and 46.9%, respectively. Major complications included nasopharyngeal necrosis with headache, necrosis of cervical vertebrae with atlantoaxial instability, temporal lobe necrosis, and palsy of the cranial nerves. The afterloaded mold was as effective as the preloaded version, but with fewer complications.Conclusions: Intracavitary mold brachytherapy was effective in salvaging NPC with early-stage local persistence or first recurrence. [Copyright &y& Elsevier]

Purpose: To evaluate the role of radioiodine and external radiotherapy treatment in papillary thyroid carcinoma (PTC).Methods and Materials: This is a retrospective study of 842 patients with the diagnosis of PTC registered from 1960 to 1997 at the Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong. The mean follow-up was 9.2 years. The stage distribution according to UICC/AJCC TNM staging was as follows: 58.6%, Stage I; 9.6%, Stage II; 26.1%, Stage III; 2.3%, Stage IV; and 3.4%, not stated.Results: The 10-year cause-specific survival (CSS) rates were as follows: Stage I, 99.8%; Stage II, 91.8%; Stage III, 77.4%; and Stage IV, 37.1%. Multivariate analysis showed that the statistically significant poor prognostic factors for CSS were as follows: age older than 45, postoperative gross locoregional (LR) residual disease, distant metastasis (DM) at presentation, and lack of radioactive iodine (RAI) treatment. In patients with no DM and no postoperative LR disease, adjuvant RAI ablation reduced both LR failure (RR [relative risk] = 0.29) and DM (RR = 0.2), although the CSS was not affected. In the subgroup of T1N0 M0 disease, no patient with RAI treatment had a relapse. External radiotherapy reduced the risk of LR failure to 0.35. Subgroup analysis revealed that external radiotherapy was particularly effective in increasing the probability of LR control of disease in patients with gross postoperative LR disease (RR = 0.36).Conclusions: Both RAI and external radiotherapy were effective treatment in PTC. Total or near-total thyroidectomy followed by RAI treatment appears to result in the best outcome. External radiotherapy to improve LR control is indicated in patients with gross postoperative residual disease. Treatment should be individualized for patients with T1N0 M0 disease. [Copyright &y& Elsevier]