GEM Study Research Articles

A Study of the Gems in a Ciborium from Einsiedeln Abbey

A Study of the Gems in a Ciborium from Einsiedeln Abbey

ENTREPRENEURSHIP AMONG RUSSIAN IMMIGRANTS IN NORWAY AND THEIR STAY-AT-HOME PEERS

The level of self-employment among immigrants is often higher than among natives. The purpose of this paper was to test empirically whether selective migration with respect to entrepreneurial characteristics may explain this difference. The relevant hypotheses were tested comparing representative samples of Russian immigrants in Norway and their stay-at-home counterparts. Data from the Russian population came from the 2008 GEM study, while data on Russian immigrants in Norway were collected through a specially designed postal survey. The analysis revealed some demographic dissimilarity between the two groups, as well as a presence of selective migration with respect to entrepreneurial characteristics. This study demonstrates that immigrants (as compared to non-migrants) are more likely to report intentions to start a business. Moreover, they possess relatively large amount of specific human capital, social capital and self-confidence relevant for entrepreneurship. The paper concludes with proposed practical implications and suggestions for further research.

Gas-gain study of standard CERN GEM and [formula omitted] Thick GEM in low-pressure He/CO 2 mixed gas

We have evaluated and compared the performances of a 50 ‐ μ m -thick CERN GEM and a 400 ‐ μ m -thick Thick GEM in low-pressure He/CO 2 (90%/10%) mixed gas. In particular, the empirical gas gains of the standard CERN GEM and the Thick GEM have been measured and investigated.

MC1R genotype may modify the effect of sun exposure on melanoma risk in the GEM study

We investigated whether MC1R genotype modifies the effect of sun exposure on melanoma risk in 1,018 cases with multiple melanomas (MPM) and 1,875 controls with one melanoma (SPM). There was some suggestion that MC1R genotype modified the effect of beach and water activities on MPM risk: ORs were 1.94 (95% CI 1.40-2.70) for any activities for no R variants and 1.39 (95% CI 1.05-1.84) with R variants (R151C, R160W, D294H, and D84E) (p for interaction 0.08). MC1R modification of sun exposure effects appeared most evident for MPM of the head and neck: for early life ambient UV, the OR was 4.23 (95% CI 1.76-10.20) with no R and 1.04 (95% CI 0.40-2.68) with R (p for interaction = 0.01; p for three-way interaction = 0.01). Phenotype modified the effect of sun exposure and MPM in a similar manner. We conclude that MC1R and pigmentary phenotype may modify the effects of sun exposure on melanoma risk on more continuously sun-exposed skin. Possible explanations include that risk may saturate with higher sun sensitivity for melanomas on continuously sun-exposed sites but continue to increase as sun exposure increases with lower sun sensitivity, or that sun-sensitive people adapt their behavior by increasing sun protection when exposed.

A phase II randomized double blind multicenter trial of gemcitabine (Gem) plus imexon (IMX) versus Gem plus placebo (P) in patients with chemotherapy-naïve pancreatic adenocarcinoma (PC).

4076 Background: Imexon (Amplimexon) is a novel cyanoaziridine (MW: 111) which depletes thiols inducing oxidative stress and apoptosis. Like Gem, IMX inhibits ribonucleotide reductase and has synergistic cytotoxicity with Gem. In a phase I study of Gem plus IMX in PC, the combination was well tolerated at full doses of both drugs, with toxicity and overall survival comparable to historical controls with Gem alone. This phase II study assessed the efficacy of the combination compared to single agent Gem in a double blind, placebo controlled design. Methods: Patients were required to have metastatic (stage IV) PC, be chemotherapy naïve, have measurable disease and laboratory values within customary limits for a study in PC. A total of 142 PC patients were randomized at 34 US sites, to receive Gem at 1,000 mg/m2 on days 1, 8, 15 of a 28 day cycle and either IMX or IMX P at 875 mg/m2 on days 1, 8 and 15 of the cycle. IMX or IMX P was given over 60 minutes followed by Gem over 30 minutes. The primary endpoint of the study was overall survival with secondary endpoints being progression free survival, 6-month and one-year survival, response rate and toxicity. The study was blinded with Data Monitoring Committee oversight with the first efficacy analysis after 100 deaths. Accrual occurred from May 2008 to May 2009. Patient characteristics for the entire group were: median age 65 years (range 37-88), male/female ratio 56/44, ECOG PS 0/1 (%): 30/70 and metastatic (number):142. Anticipated toxicities based on our prior studies of the combination include fatigue, anemia, nausea, vomiting, leukopenia and abdominal pain. There were 32 serious adverse events which were considered possibly, probably or definitely related to the study regimens and included (by CTCAE category) gastrointestinal, infection, pain, blood bone marrow, constitutional symptoms pulmonary/respiratory, and one each in 7 other categories. As the study remains blinded, we cannot attribute the toxicity data to either arm of the study. The results of this study are anticipated between March and July of 2010 and if appropriate will form the basis of a phase III confirmatory study. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AmpliMed Corporation AmpliMed Corporation AmpliMed Corporation

Validity of the Finnish Prescription Register for Measuring Psychotropic Drug Exposures among Elderly Finns

Pharmacoepidemiological studies assessing the associations between psychotropic drug use and adverse events in the elderly frequently employ automated pharmacy databases as the source of exposure data. However, information on the validity of these databases for estimating psychotropic drug exposures in elderly people is scarce. This study evaluated the validity of the Finnish Prescription Register for estimating current exposures to psychotropic drugs in elderly people. Furthermore, the potential change in the validity over time was determined. This was a population-based intervention study (GeMS; Geriatric Multidisciplinary Strategy for the Good Care of the Elderly) conducted between 2004 and 2007. Initially, 1000 randomly selected persons aged >or=75 years living in the City of Kuopio, Finland, in November 2003 were invited to participate in the study. Of these, 716 agreed to participate at baseline (2004) and 570 were still available for 3-year follow-up (2007). The validity of the Prescription Register was assessed by comparing it with the self-reported information collected by interviews in 2004 and in 2007 in the GeMS study. Using the self-reported data as a reference standard, sensitivity, specificity and Cohen's kappa statistic (measure of inter-rater agreement for qualitative [categorical] items) with 95% confidence intervals were computed for different categories and subcategories of psychotropic drugs, applying fixed-time windows of 4, 6 and 12 months. In 2007, the sensitivity varied between psychotropic categories and subcategories, being generally highest with the 12-month time window (0.57-0.96). The specificity was highest with the 4-month time window (0.94-0.99), showing a slight tendency to decrease with an extended time window. The sensitivity and specificity were highest for antidepressants and antipsychotics, followed by benzodiazepines. The agreement was almost perfect (kappa = 0.81-1.00) or substantial (kappa = 0.61-0.80) for all categories and subcategories of psychotropic drugs. Few differences in validity were observed between the two years. Using self-reported data as a reference standard, the Prescription Register provides valid information on current exposures to antidepressants and antipsychotics in elderly people if the time window is selected with adequate consideration. However, the validity is lower for benzodiazepines, suggesting that other sources of information should be considered when performing pharmacoepidemiological studies.

MC1R genotype may modify the effect of sun exposure on melanoma risk in the GEM study

MC1R genotype may modify the effect of sun exposure on melanoma risk in the GEM study

GOFURTGO trial (GFG): An AGITG multicenter phase II study of fixed dose rate gemcitabine-oxaliplatin (Gem-Ox) integrated with concomitant 5FU and 3-D conformal radiotherapy (5FU-3DRT) for the treatment of locally advanced pancreatic cancer (LAPC)

4616 Background: Our previous study of Gem with sandwich 5FU-3DRT for LAPC was encouraging (Br J Cancer 2007: 97, 464–471). Gem-Ox has higher response rate than Gem, improved progression free survival (PFS) but not overall survival (OS). Its use in LAPC may improve local control (LC) and delay systemic spread. GFG is a study of induction (ind) Gem-Ox, then 5FU-3DRT, then consolidation (con) Gem-Ox. Primary outcome is feasibility using proportion of patients (pts) receiving > 80% planned dose for each component. Secondary outcomes are safety, activity and QOL. Methods: Pts with previously untreated inoperable LAPC, M0, measurable disease, ECOG 0–2 were given Gem (1000mg/m2 d1 + d15 q28), Ox (100mg/m2 d2 + d16 q28) in both ind (1 cycle) & con (3 cycles), & 5FU 200mg/m2/d over 6 weeks during RT of 54Gy in 30 fractions of 1.8Gy. Results: 48 pts were enrolled, median age 61y (44–81y), PS 0/1=96%, regional lymph nodes=44%, T4=46%. Worst grade (G) for anaemia (10%); fatigue, nausea (8%); diarrhoea, vomiting, neutropenia, infection (4%); stomatitis, anorexia (2%) was G3. Thrombocytopenia was G3=2% G4=2%; liver function was G3=23% G4=6%; late radiation toxicity was G3=2% G4=2% (both gastric bleeding). Half of all pts completed all planned cycles (24 pts); 29% of pts received >80% of all treatment (14 pts); 70% of pts received >80% of all chemoradiation (33 pts). Pts ceased treatment for toxicity (16%), PD (21%) or doctor/pt preference (4/2%). Global QOL did not significantly change from baseline. Median duration of LC, PFS, OS were 15.8, 9.9, 15.4m at median follow up of 29.7m. Exploratory analysis of age, disease stage, PS, CA19–9 or WCC found no univariate predictors of PFS or treatment completion. 8/48 pts survived >24m. Conclusions: Compared to our previous study using the same radiation schedule, addition of oxaliplatin was associated with improved LC, PFS & OS (prev. 11.9, 7.1 & 11.7m) without significant offset by toxicity. The extended duration of LC and a subset who had a very prolonged benefit may be due to patient selection but equally may suggest an incremental benefit from more intensive systemic therapy requiring further study in controlled trials. [Table: see text]

Gemcitabine (gem) can enhance immunotherapy (IT) of pancreatic cancer – importance of schedule

With a 5‐year survival rate of only 4%, non‐resectable pancreatic cancer is in urgent need of novel approaches to supplement current therapies. This study assessed parameters for combining gem and IT with the anti‐MUC1 antibody, AR20.5. Upon injection, AR20.5 forms immune complexes with circulating MUC1, leading to enhanced T cell immunity. To examine the effects of gem on immune cells and antigen processing, three parallel approaches were conducted: a) an in vitro co‐culture system of immature DC, tumor and T cells; b) a time course study of gem (60 mg/kg) in Panc02 tumor bearing mice; and c) a combination chemo‐IT study in MUC1‐transgenic mice with established Panc02.MUC1 tumors. In vitro, gem did not affect T cell or DC survival at concentrations ≤5 μg/mL. Interestingly, gem enhanced maturation of DC and T cell proliferation to non‐specific stimuli (anti‐CD3/CD28) as well as to the co‐cultured tumor cells. The in vivo time course study confirmed minor effects of gem on T and B cell survival with rapid recovery. Gem increased DC maturation in the spleen and tumor as well as DC migration to the tumor by Day 5. Further, gem significantly reduced T regs in the draining LN (Day 7) and tumor (Day 10). Reduction in myeloid derived suppressor cells was transient (Day 5–7) in spleen and tumor. Tumor control studies showed synergistic effects for combination gem‐IT over single agents when IT was given 1 week delayed relative to gem.

Genetic and phenotypic architecture of metabolic syndrome-associated components in dyslipidemic and normolipidemic subjects: The GEMS Study

Atherogenic dyslipidemia, manifest by low HDL-cholesterol and high TG levels, is an important component of ATP-III defined metabolic syndrome. Here, we dissected the phenotypic and genetic architecture of these traits by assessing their relationships with other metabolically relevant measures, including plasma adipo-cytokines, highly sensitive C-reactive protein (hsCRP) and LDL particle size, in a large family data set (n=2800) and in an independent set of dyslipidemic cases (n=716) and normolipidemic controls (n=1073). We explored the relationships among these phenotypes using variable clustering and then estimated their genetic heritabilities and cross-trait correlations. In families, four clusters explained 61% of the total variance, with one adiposity-related cluster (including hsCRP), one BP-related cluster, and two lipid-related clusters (HDL-C, TG, adiponectin and LDL particle size; apoB and non-HDL-C). A similar structure was observed in dyslipidemic cases and normolipidemic controls. The genetic correlations in the families largely paralleled the phenotype clustering results, suggesting that common genes having pleiotropic effects contributed to the correlations observed. In summary, our analyses support a model of metabolic syndrome with two major components, body fat and lipids, each with two subcomponents, and quantifies their degree of overlap with each other and with metabolic-syndrome related measures (adipokines, LDL particle size and hsCRP).

Los entalles de Segobriga y su territorio

Study of engraved gems found in the archaeological excavations in the Roman city of Segobriga (Conventus Carthagunensis , Saelices, Cuenca). This group is made up of twelve gems, best representing sacred images. All of them are engraved either in quartz or in glass paste.

Two-drug gemcitabine-based first-line treatment of elderly patients (pts) with small cell lung cancer (SCLC): The G-STEP program

7089 Background: Trials testing chemotherapy for elderly pts with SCLC are scanty. Gemcitabine (Gem) is active and well tolerated. The G-STEP program looked for optimal 2-drug combination of G with either vinorelbine (Vin), etoposide (Eto), cisplatin (Cis), or carboplatin (Car). Methods: Extended stage SCLC pts, aged >70 years, PS 0–2, were eligible. Dose of G was 1,000 mg/m2, dd 1&8, every 3 weeks in all the four combinations. As safety data in the elderly were already available for Gem+Vin (Vin dose 25 mg/m2, dd 1&8), a two-stage minimax flexible design was applied with response as end-point: ≥13 responses/30 pts required at 1st stage, with p0=0.40, p1=0.60, α and β=0.10. For Gem+Car, Gem+Cis, Gem+Eto a phase 1–2 Bayesian design to select optimal dose was applied (Thall & Russell, Biometrics, 1998), with 3 possible outcomes for each patient: “active” (response and no unacceptable toxicity [UT]), “inactive” (no response, no UT), or “toxic” (UT independently of response). A response rate [RR] ≥60% and a rate of UT ≤25% were acceptable. Dose levels to explore were: Car: AUC 3.5 / 4 / 4.5, d1; Cis: 50 / 60 / 70 mg/m2, d1; Eto: 60 / 70 / 80 mg/m2, dd 1,2,3. Results: From May 2000 to September 2005, 78 eligible pts were enrolled; median age was 74 years (42% of pts older than 75yrs). In the whole group, median progression-free survival and overall survival were 20.3 weeks (95% CI 17.6 - 24.1) and 33.7 weeks (95% CI 23.7 - 41.6), respectively. Study of Gem+Vin was closed for inactivity after 1st stage with 11 responses / 30 pts (RR 36.7%, 95% exact CI: 19.9–56.1). Gem+Eto arm was closed after 10 pts (5 inactive and 5 toxic) because too high probability (0.994) of inactivity. Gem+Cis arm was closed after 12 pts (2 active, 5 inactive, 5 toxic) because too high probability (0.988) of inactivity. With Gem+Car (December 2005: 2 pts ongoing, 24 analysed: 12 active, 6, inactive and 6 toxic), RR in the 20 pts receiving Car at AUC 3.5 was 60% (95% exact CI: 36.1–80.9). Conclusions: The combination of gemcitabine and carboplatin seems promising for future trials in elderly patients with extended SCLC. The G-STEP program was supported by GIOGER. No significant financial relationships to disclose.

A design for cancer case–control studies using only incident cases: experience with the GEM study of melanoma

The population-based case-control study is not suited to the evaluation of rare genetic (or environmental) factors. The use of a novel case-control design in which cases have second primaries and controls are cancer survivors has been proposed for this purpose. We report results from an international study of melanoma that involved population-based ascertainment of incident cases of second or subsequent primary melanoma as the 'case' group and incident cases of first primary melanoma as the 'control' group. We evaluate the validity of the study design by comparing the results obtained for phenotypic factors that have been shown consistently to be associated with melanoma in previous conventional studies with the results from a conventional case-control study conducted in Connecticut and from literature reviews. All but one of the known risk factors for melanoma were shown to be significantly associated with melanoma in our study, though the individual odds ratios appear to be somewhat attenuated relative to the magnitudes typically observed in the literature. Patients with a second or subsequent primary cancer of a single type represent a potentially valuable and under-utilized resource for the study of cancer aetiology.

Phase I study of imatinib mesylate and gemcitabine in patients with refractory solid tumor malignancy

3100 Background: Based on the preclinical activity of Gemcitabine (Gem) and imatinib mesylate (IM) (Gleevec) in combination (R. Hwang et al, 2003), a phase I study of Gem+IM was developed to determine MTDs for both Gem and IM when administered in combination. The study also assesses Gem PK in the presence and absence of IM. Methods: Patients (pts) with refractory malignancy; intact intestinal absorption, measurable/evaluable disease, adequate hepatic, renal and hematologic function; PS 0–2 and survival time > 3 months who signed informed consent were eligible. Pts were treated at 10 dose levels. Gem, administered by fixed dose rate infusion, 10 mg/m2/min, had an initial schedule of 600 mg/m2 d1,8,15 q28d. Dose was decreased due to toxicity to 450 mg/m2/ d 3,10 q 21d and, subsequently, re- escalated to 1000 mg/m2 d 3,10 q21 days. IM dose started at 300 mg qd, was deescalated to 300 mg, d1–5 and 8–12 and escalated to 400 mg/d 1–5 and 8–12 q21d. Results: 24 men and 10 women, median age 62 (range 28–83) recei...

An aging study of triple GEMs in Ar–CO 2

An aging study was performed using triple GEMs and a print circuit board (PCB) with an intense X-ray radiation source. The GEM chamber consists of three identical GEMs and a large gas gain (6000) was shared by them. The chamber and its gas circulation line was carefully cleaned and constructed with stainless steel materials. The detector was irradiated continuously about 750 h without interruption until a large amount of charge was accumulated. A single-wire counter served as a monitoring device to check the beam and ambient conditions. The quality of the Ar–CO 2 gas was checked by gas chromatography and no measurable amount of hydrocarbons were found. 27 mC/mm 2 was accumulated with no noticeable degradation and no deposit or discoloration was found in an optical check.

The prevalence and characteristics of migraine in a population-based cohort: the GEM study.

To describe the distribution of migraine and its subtypes in the general population. Previous population-based studies are limited by small samples or a narrow age range, do not provide prevalence estimates of migraine with and without aura, or underestimate prevalence by not accounting for patients missed as a result of using imperfect screening instruments. The participants in the Genetic Epidemiology of Migraine Study were comprised of 6,491 adults, age 20 to 65 years, selected randomly from two county population registries in the Netherlands to participate in a general health survey (52.7% response). Migraineurs were identified as follows: All participants were screened on headache history. Those meeting screen-positive criteria were given a detailed questionnaire on headache. A total of 1,292 randomly selected screen-positives (83% of screen-positives) and 197 randomly selected screen-negatives (5% of screen-negatives) were administered a semistructured clinical interview by telephone. Final diagnosis met 1988 International Headache Society criteria. Prevalence of migraine was estimated for sex and 5-year age strata. The lifetime prevalence of migraine in women was 33% and the 1-year prevalence of migraine in women was 25%. In men, the lifetime prevalence was 13.3% and the 1-year prevalence was 7.5%. Among patients with migraine in the past year, 63.9% had migraine without aura, 17.9% had migraine with aura, and 13.1% had migraine both with and without aura. The prevalence of migraine was significantly higher in women and not associated with socioeconomic status. Migraineurs suffered a median of 12 migraine attacks per year; 25% had at least two attacks per month. The prevalence of migraine is higher then previously reported. The coexistence of migraine with and without aura occurs frequently and has implications for future studies on the genetics of migraine.

Temporal process from receptors to higher brain in taste detection studied by gustatory-evoked magnetic fields and reaction times.

Using magnetoencephalography (MEG) and a taste stimulator with rapid-rise time, we previously located the primary gustatory area in the human cerebral cortex and also investigated the relation between the onset latency of the gustatory-evoked magnetic fields (GEM) and reaction times (RT) in different taste qualities. In the present study, we investigated the temporal process from receptors to the higher brain in taste detection based on the results of the GEM and RT of different tastes. We used 100 mM, 300 mM and 1 M NaCl and 3 mM saccharine. The duration of each stimulus was 400 ms. The interstimulus interval was approximately 30 s. The temperature of both taste solution and deionized water was maintained the same as that of the tongue. Four subjects participated in this experiment. The 64-channel whole-head SQUID system (CTF Systems Inc., Canada) was used to measure GEM. The sampling rate was 250 Hz, and the low-pass filter was 40 Hz. In each subject, GEM and RT to a given taste were measured separately by applying 40 trials of stimulation. After each trial of both measurements, subjects showed a perceived intensity by using their fingers. In the GEM study, the trials contaminated with eye movements were rejected and the remaining trials were averaged. Averaged GEM were super-imposed on the same sheet with all 64 channels to measure the onset latency of GEM from the stimulus onset. RT and onset latencies of GEM were longer for saccharine than NaCl, and the value of RT minus the onset latency of GEM from RT, presumably indicating the time for higher brain process plus motor process, did not differ between 3 mM saccharine and 1 M NaCl. With increased concentrations of NaCl, RT became shorter, but onset latencies of GEM remained constant. Sweet taste took a longer time than salty taste at receptor process including the time for diffusion to receptors.

Use of spectroscopic techniques for the study of natural and synthetic gems: application to rubies

Spectroscopic techniques were applied to the study of natural and synthetic gems, especially rubies. It is shown that among the spectroscopic techniques available, micro-Raman spectroscopy is the easiest to use and the most efficient. Moreover, this technique can be applied to mounted gems without removing them from the setting. However, complementary methods such as micro-Fourier transform infrared, micro-fluorescence, electron probe and NMR spectroscopy, were used in order to characterize the gems more thoroughly in order to differentiate between natural and synthetic specimens. © 1997 John Wiley & Sons, Ltd.

Use of spectroscopic techniques for the study of natural and synthetic gems: application to rubies

Spectroscopic techniques were applied to the study of natural and synthetic gems, especially rubies, It is shown that among the spectroscopic techniques available, micro-Raman spectroscopy is the easiest to use and the most efficient Moreover, this technique can be applied to mounted gems without removing them from the setting. However, complementary methods such as micro-Fourier transform infrared, micro-fluorescence, electron probe and MMR spectroscopy, were used in order to characterize the gems more thoroughly in order to differentiate between natural and synthetic specimens. (C) 1997 John Wiley & Sons, Ltd.

Time-resolved spectroscopy of IR Gem at quiescence

We present some preliminary results of a spectroscopic study of the cataclysmic system IR Gem at quiescence during two orbital periods.