Homological description of crystal structures on quiver varieties

Using methods of homological algebra, we obtain an explicit crystal isomorphism between two realizations of crystal bases of the lower part of the quantized enveloping algebra and the irreducible highest weight representations of (almost all) simply-laced Lie algebras, respectively. The first realization we consider is a geometric construction in terms of irreducible components of certain quiver varieties established by Kashiwara and Saito. The second is a realization in terms of isomorphism classes of quiver representations obtained by Reineke using Ringel's Hall algebra approach to quantum groups. We connect the two constructions by studying certain sufficiently generic representations of the preprojective algebra. We further show that, in the type $A$ situation, the crystal isomorphism can be described on the combinatorial level via semistandard Young tableaux

The impact of continuous glucose monitoring (CGM) on low interstitial glucose values and low blood glucose values assessed by Point-of-Care glucose meters (POC-GM).

The impact of CGM on the duration of periods with low glucose measured in interstitial fl uid is well known. But studies showing an impact of CGM on low blood glucose values, measured by POC-GM are rare. This crossover study examines the impact of CGM on duration of periods spent in low interstitial glucose range (70 mg/dl) as well as on the proportion of low blood glucose (BG) values measured by POC-GM (Glukometer 3000, Bio Sensor Technology, Germany)and time until detection of low BG by use of POC-GM. 41 type 1 diabetic patients (age 42.0 ±11.3 yrs, diabetes duration 15.3 ±10.1; A1c 8.2 ±1.4%) used the DEXCOM 7 Plus CGM system twice; once participants were blinded against the results and in the other study phase (Open GCM) patients received real-time glucose values and current glucose trends, used the CGM data to determine their insulin dose, and were alerted if hypoglycaemic or hyperglycaemic glucose ranges were approached. In addition, BG was routinely measured 6 times a day by POC-GM. The order of study phases was randomized. The time spent in a hypoglycaemic glucose range (< 70 mg/dl) was reduced by open CGM from 180.6 ±125 to 125 ± 89.2 minutes per day (p=.005). Also time spent in the euglycemic glucose range was increased from 946 ±176 to 1023 ±168 minutes per day (p=.003). Open CGM reduced the proportion of low BG measurements by POC-GM from 10.3 ±7.6% to 7.4 ±5.8% (p=.039), whereas the euglycemic POC readings was increased from 68.3 ±12.1% to 73.7 ±12.1% (p=.007). The time until a hypoglycaemic BG value was detected by POC-GM was signifi cantly (p.028) shortened by 33.1 (95% CI 3.8 -62.3) minutes. These results demonstrate that CGM used for insulin dosing and hypoglycaemia alerts not only diminishes low interstitial glucose values but also reduces the proportion of low BG measured by POC-GM. In addition the time for the detection of a hypoglycaemic episode by POC-GM was signifi cantly shortene

The impact of continuous glucose monitoring (CGM) on low interstitial glucose values and low blood glucose values assessed by Point-of-Care glucose meters (POC-GM).

The impact of CGM on the duration of periods with low glucose measured in interstitial fluid is well known. But studies showing an impact of CGM on low blood glucose values, measured by POC-GM are rare. This crossover study examines the impact of CGM on duration of periods spent in low interstitial glucose range (70 mg/dl) as well as on the proportion of low blood glucose (BG) values measured by POC-GM (Glukometer 3000, Bio Sensor Technology, Germany)and time until detection of low BG by use of POC-GM. 41 type 1 diabetic patients (age 42.0 ±11.3 yrs, diabetes duration 15.3 ±10.1; A1c 8.2 ±1.4%) used the DEXCOM 7 Plus CGM system twice; once participants were blinded against the results and in the other study phase (Open GCM) patients received real-time glucose values and current glucose trends, used the CGM data to determine their insulin dose, and were alerted if hypoglycaemic or hyperglycaemic glucose ranges were approached. In addition, BG was routinely measured 6 times a day by POC-GM. The order of study phases was randomized. The time spent in a hypoglycaemic glucose range (< 70 mg/dl) was reduced by open CGM from 180.6 ±125 to 125 ± 89.2 minutes per day (p=.005). Also time spent in the euglycemic glucose range was increased from 946 ±176 to 1023 ±168 minutes per day (p=.003). Open CGM reduced the proportion of low BG measurements by POC-GM from 10.3 ±7.6% to 7.4 ±5.8% (p=.039), whereas the euglycemic POC readings was increased from 68.3 ±12.1% to 73.7 ±12.1% (p=.007). The time until a hypoglycaemic BG value was detected by POC-GM was signifi cantly (p.028) shortened by 33.1 (95% CI 3.8 -62.3) minutes. These results demonstrate that CGM used for insulin dosing and hypoglycaemia alerts not only diminishes low interstitial glucose values but also reduces the proportion of low BG measured by POC-GM. In addition the time for the detection of a hypoglycaemic episode by POC-GM was significantly shortene

The Impact of Continuous Glucose Monitoring on Low Interstitial Glucose Values and Low Blood Glucose Values Assessed by Point-of-care Blood Glucose Meters : Results of a Crossover Trial

Objective: In a randomized crossover trial the impact of continuous glucose monitoring (CGM) was tested on the occurrence of low blood glucose values measured by point of care (POC) measurement and on low glucose values measured by CGM in the interstitial fluid. Methods: A total of 41 type 1 diabetic patients (age 42.0 ± 11.4 years, diabetes duration 15.3 ± 10.1 years, A1c 8.2 ± 1.4%) used a CGM system (Dexcom SEVEN PLUS system) twice. In first study phase (CGM blind), patients were blind regarding the CGM current glucose levels and were not alerted when critical glucose values were reached. In the second phase (CGM real time), patients had access to current glucose levels and were alerted if critical glucose values were reached. Results: During CGM real time the proportion of hypoglycemic POC blood glucose values were significantly reduced (7.5 ± 5.6% vs 10.1 ± 7.5%; P = .04), whereas the proportion of euglycemic blood glucose values were significantly enhanced (73.7 ± 18.3% vs 68.3 ± 12.1%; P = .01). The duration of low glucose periods in the interstitial fluid was significantly lower in the CGM real time phase (125 ± 89 vs 181 ± 125 minutes per day; P = .005). The time until a low blood glucose was detected by POC measurement was shortened by 33.2 ± 76.1 minutes (P = .03). Conclusion: The study demonstrated that CGM is able to not only reduce duration of hypoglycemia measured by CGM in interstitial fluid, but also reduce the proportion of low POC blood glucose measurements. In addition, hypoglycemia can be detected earlier

Combinatorics of canonical bases revisited

We give a formula for the crystal structure on the integer points of the string polytopes and the *-crystal structure on the integer points of the string cones of type A for arbitrary reduced words. As a byproduct, we obtain defining inequalities for Nakashima–Zelevinsky string polytopes. Furthermore, we give an explicit description of the Kashiwara *-involution on string data for a special choice of reduced word

Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial.

BACKGROUND: Necitumumab is a second-generation, recombinant, human immunoglobulin G1 EGFR antibody. In this study, we aimed to compare treatment with necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone in patients with previously untreated stage IV squamous non-small-cell lung cancer. METHODS: We did this open-label, randomised phase 3 study at 184 investigative sites in 26 countries. Patients aged 18 years or older with histologically or cytologically confirmed stage IV squamous non-small-cell lung cancer, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and adequate organ function and who had not received previous chemotherapy for their disease were eligible for inclusion. Enrolled patients were randomly assigned centrally 1:1 to a maximum of six 3-week cycles of gemcitabine and cisplastin chemotherapy with or without necitumumab according to a block randomisation scheme (block size of four) by a telephone-based interactive voice response system or interactive web response system. Chemotherapy was gemcitabine 1250 mg/m(2) administered intravenously over 30 min on days 1 and 8 of a 3-week cycle and cisplatin 75 mg/m(2) administered intravenously over 120 min on day 1 of a 3-week cycle. Necitumumab 800 mg, administered intravenously over a minimum of 50 min on days 1 and 8, was continued after the end of chemotherapy until disease progression or intolerable toxic side-effects occurred. Randomisation was stratified by ECOG performance status and geographical region. Neither physicians nor patients were masked to group assignment because of the expected occurrence of acne-like rash--a class effect of EGFR antibodies--that would have unmasked most patients and investigators to treatment. The primary endpoint was overall survival, analysed by intention to treat. We report the final clinical analysis. This study is registered with ClinicalTrials.gov, number NCT00981058. FINDINGS: Between Jan 7, 2010, and Feb 22, 2012, we enrolled 1093 patients and randomly assigned them to receive necitumumab plus gemcitabine and cisplatin (n=545) or gemcitabine and cisplatin (n=548). Overall survival was significantly longer in the necitumumab plus gemcitabine and cisplatin group than in the gemcitabine and cisplatin alone group (median 11.5 months [95% CI 10.4-12.6]) vs 9.9 months [8.9-11.1]; stratified hazard ratio 0.84 [95% CI 0.74-0.96; p=0.01]). In the necitumumab plus gemcitabine and cisplatin group, the number of patients with at least one grade 3 or worse adverse event was higher (388 [72%] of 538 patients) than in the gemcitabine and cisplatin group (333 [62%] of 541), as was the incidence of serious adverse events (257 [48%] of 538 patients vs 203 [38%] of 541). More patients in the necitumumab plus gemcitabine and cisplatin group had grade 3-4 hypomagnesaemia (47 [9%] of 538 patients in the necitumumab plus gemcitabine and cisplatin group vs six [1%] of 541 in the gemcitabine and cisplatin group) and grade 3 rash (20 [4%] vs one [<1%]). Including events related to disease progression, adverse events with an outcome of death were reported for 66 (12%) of 538 patients in the necitumumab plus gemcitabine and cisplatin group and 57 (11%) of 541 patients in the gemcitabine and cisplatin group; these were deemed to be related to study drugs in 15 (3%) and ten (2%) patients, respectively. Overall, we found that the safety profile of necitumumab plus gemcitabine and cisplatin was acceptable and in line with expectations. INTERPRETATION: Our findings show that the addition of necitumumab to gemcitabine and cisplatin chemotherapy improves overall survival in patients with advanced squamous non-small-cell lung cancer and represents a new first-line treatment option for this disease. FUNDING: Eli Lilly and Company

Necitumumab plus pemetrexed and cisplatin as first-line therapy in patients with stage IV non-squamous non-small-cell lung cancer (INSPIRE): an open-label, randomised, controlled phase 3 study.

BACKGROUND: Necitumumab is a second-generation recombinant human immunoglobulin G1 EGFR monoclonal antibody that competitively inhibits ligand binding. We aimed to compare necitumumab plus pemetrexed and cisplatin with pemetrexed and cisplatin alone in patients with previously untreated, stage IV, non-squamous non-small-cell lung cancer (NSCLC). METHODS: We did this randomised, open-label, controlled phase 3 study at 103 sites in 20 countries. Patients aged 18 years or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and adequate organ function, were randomly assigned 1:1 to treatment with a block randomisation scheme (block size of four) via a telephone-based interactive voice-response system or interactive web-response system. Patients received either cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 of a 3-week cycle for a maximum of six cycles alone, or with necitumumab 800 mg on days 1 and 8. Necitumumab was continued after the end of chemotherapy until disease progression or unacceptable toxic effects. Randomisation was stratified by smoking history, ECOG performance status, disease histology, and geographical region. Patients and study investigators were not masked to group assignment. The primary endpoint was overall survival. Efficacy analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00982111. FINDINGS: Between Nov 11, 2009, and Feb 2, 2011, we randomly assigned 633 patients to receive either necitumumab plus pemetrexed and cisplatin (n=315) or pemetrexed and cisplatin alone (n=318). Enrolment was stopped on Feb 2, 2011, after a recommendation from the independent data monitoring committee. There was no significant difference in overall survival between treatment groups, with a median overall survival of 11.3 months (95% CI 9.5-13.4) in the necitumumab plus pemetrexed and cisplatin group versus 11.5 months (10.1-13.1) in the pemetrexed and cisplatin group (hazard ratio 1.01 [95% CI 0.84-1.21]; p=0.96). The incidence of grade 3 or worse adverse events, including deaths, was higher in the necitumumab plus pemetrexed and cisplatin group than in the pemetrexed and cisplatin group; in particular, deaths regarded as related to study drug were reported in 15 (5%) of 304 patients in the necitumumab group versus nine (3%) of 312 patients in the pemetrexed and cisplatin group. Serious adverse events were likewise more frequent in the necitumumab plus pemetrexed and cisplatin group than in the pemetrexed and cisplatin group (155 [51%] of 304 vs 127 [41%] of 312 patients). Patients in the necitumumab plus pemetrexed and cisplatin group had more grade 3-4 rash (45 [15%] of 304 vs one [<1%] of 312 patients in the pemetrexed and cisplatin alone group), hypomagnesaemia (23 [8%] vs seven [2%] patients), and grade 3 or higher venous thromboembolic events (23 [8%] vs 11 [4%] patients) than did those in the pemetrexed and cisplatin alone group. INTERPRETATION: Our findings show no evidence to suggest that the addition of necitumumab to pemetrexed and cisplatin increases survival of previously untreated patients with stage IV non-squamous NSCLC. Unless future studies identify potentially useful predictive biomarkers, necitumumab is unlikely to provide benefit in this patient population when combined with pemetrexed and cisplatin. FUNDING: Eli Lilly and Company