Genetics of phenological development and implications for seed yield in lentil.

Understanding phenology, its genetics and agronomic consequences, is critical for crop adaptation. Here we aim at (1) characterising lentil response to photoperiod with a focus on five loci: the lentil ELF3 ortholog Sn, two loci linked to clusters of lentil FT orthologs and two loci without candidates in chromosomes 2 and 5 (exp. 1: 36 lines, short and long day in phytotron); (2) establishing phenology-yield relationship (exp. 2: 25 lines, 11 field environments). A vintage perspective, where we quantify time trends in phenotype over three decades of breeding, links both experiments. Yield increased linearly from older to newer varieties at 29 kg ha-1 yr-1 or 1.5% yr-1, correlated negatively with flowering time in both winter- and summer-rainfall regimes, and decoupled from biomass in favourable environments. Time to flowering shortened from older to newer varieties at -0.56 % yr-1 in the field, and -0.42 % yr-1 (short day) and -0.99 % yr-1 (long day) in the phytotron. Early-flowering lines of diverse origin carried multiple early alleles for the five loci, indicating that at least some of these loci affect phenology additively. Current germplasm primarily features the early flowering haplotype for an FTb cluster region, hence the potential to increase phenological diversity with yield implications.

Comparison of gemcitabine and carboplatin versus cisplatin and etoposide for patients with poor-prognosis small cell lung cancer.

BACKGROUND: The combination of cisplatin and etoposide (PE) has been a standard treatment for patients with poor-prognosis small cell lung cancer (SCLC). This non-inferiority design trial aimed to determine whether the combination of gemcitabine and carboplatin (GC) results in similar survival but is less toxic with better quality of life. METHODS: Previously untreated patients with SCLC with extensive disease or limited stage with poor prognostic factors were randomly assigned to six 3-weekly cycles of GC or PE. RESULTS: 241 patients (121 GC, 120 PE) were recruited, of which 216 (90%) had died. There was no difference in overall survival (HR 1.01, 95% CI 0.77 to 1.32). Median survival with GC and PE was 8.0 and 8.1 months, respectively. Median progression-free survival was 5.9 months with GC and 6.3 months with PE. Grade 3 or 4 myelosuppressions were more frequent with GC (anaemia: 14% GC vs 2% PE; leucopenia: 32% GC vs 13% PE; thrombocytopenia: 22% GC vs 4% PE), but these were not associated with increased hospital admissions, infections or fatalities. Grade 2-3 alopecia (68% PE vs 17% GC) and nausea (43% PE vs 26% GC) were more frequent with PE. Patients given GC received more chemotherapy as outpatients (89% GC vs 66% PE of treatment cycles). In QoL questionnaires, more patients receiving PE reported being upset by hair loss (p = 0.004) and impaired cognitive functioning (p = 0.04). CONCLUSIONS: GC is as effective as PE in terms of overall survival and progression-free survival and has a toxicity profile more acceptable to patients. TRIAL REGISTRATION NUMBER: ISRCTN 39679215.

Gemcitabine plus carboplatin versus mitomycin, ifosfamide, and cisplatin in patients with stage IIIB or IV non-small-cell lung cancer: a phase III randomized study of the London Lung Cancer Group.

PURPOSE: This phase III randomized trial compared two chemotherapy regimens, gemcitabine plus carboplatin and mitomycin, ifosfamide, and cisplatin, in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC). The regimens were compared with regard to effects on survival, response rates, toxicity, and quality of life. PATIENTS AND METHODS: Eligible patients had previously untreated stage IIIB or IV NSCLC suitable for cisplatin-based chemotherapy. Randomly assigned patients were to receive four cycles, each at 3-week intervals, of carboplatin area under the curve of 5 on day 1 plus gemcitabine 1,200 mg/m(2) on days 1 and 8 (GCa) or mitomycin 6 mg/m(2), ifosfamide 3g/m(2), and cisplatin 50 mg/m(2) on day 1 (MIC). RESULTS: Between February 1999 and August 2001, 422 patients (GCa, n = 212; MIC, n = 210) were randomly assigned in the United Kingdom. The majority of patients received the intended four cycles (GCa, 64%; MIC, 61%). There was a significant survival advantage for GCa compared with MIC (hazard ratio, 0.76; 95% CI, 0.61 to 0. 93; P = .008). Median survival was 10 months with GCa and 7.6 months with MIC (difference, 2.4 months; 95% CI, 1.0 to 4.0), and 1-year survival was 40% with GCa and 30% with MIC (difference, 10%; 95% CI, 3% to 18%). Overall response rates were similar (42% for GCa v 41% for MIC; P = .84). More thrombocytopenia occurred with GCa (P = .03), but this was not associated with increased hospital admission or fatality. GCa caused less nausea, vomiting, constipation, and alopecia and was associated with fewer admissions for administration and better quality of life. CONCLUSION: In patients with advanced NSCLC, GCa chemotherapy was shown to be a better-tolerated treatment that conferred a survival advantage over MIC.

Five-day oral etoposide treatment for advanced small-cell lung cancer: randomized comparison with intravenous chemotherapy.

BACKGROUND: Oral etoposide is an active single agent in small-cell lung cancer (SCLC) and is widely prescribed as first-line treatment as an alternative to intravenous combination chemotherapy in patients with extensive disease. PURPOSE: The intention of this study was to determine if the effects of oral etoposide therapy on survival and quality of life are equivalent to those of intravenous chemotherapy. METHODS: In a randomized trial of palliative treatment in advanced SCLC, oral etoposide (100 mg given twice daily for 5 days) was compared with intravenous chemotherapy consisting of alternating cycles of cisplatin and etoposide (PE) and cyclophosphamide, doxorubicin, and vincristine (CAV). Six cycles of chemotherapy were administered every 21 days in both regimens. Symptom control and quality of life were measured with the Rotterdam Symptom Checklist and a daily diary card. In January 1996, after 155 patients had been randomly assigned from a projected intake of 365 patients, an independent Data Monitoring Committee examined the interim results. Survival was determined by the Kaplan-Meier method, and the logrank test was used to compare treatments. For quality-of-life comparisons, average scores were calculated for each time point. The Mann-Whitney U test was used to determine any significant overall differences between treatments. For the Rotterdam Symptom Checklist, separate analyses were done for each subset (psychological well-being, physical symptoms, lung cancer symptoms, treatment symptoms, activity, and quality of life). Response rates and toxicity scores were compared by using chi2. All statistical tests were two-sided. RESULTS: Survival was inferior at 1 year in the oral etoposide group compared with intravenous therapy (9.8% for oral versus 19.3% for intravenous; difference = 9.5%; 95% confidence interval of difference = 0.3%-18.7%; P<.05), and there was a trend toward inferior overall survival. Median survival was 4.8 months for oral treatment and 5.9 months for intravenous therapy. Progression-free survival was worse in the oral etoposide arm (median = 3.6 months versus 5.6 months; P<.001), as well as overall response rate (32.9% versus 46.3%; P<.01). With the exception of acute nausea and vomiting associated with intravenous chemotherapy, all aspects of symptom control and quality of life were either the same or worse in the oral etoposide group. Study closure was recommended. CONCLUSIONS: These interim results show that this schedule of oral etoposide is inferior to intravenous chemotherapy in the treatment of advanced SCLC and should not be used as first-line treatment of this disease.

Production and perception of "verbosity" in younger and older adults.

Older adults produced more off-topic speech (OTS) than younger adults during autobiographical interviews in previous studies, a finding attributed to age-related deficits in inhibiting irrelevant information. In this study, older adults produced more OTS than younger adults for autobiographical topics, but not for picture descriptions. A 2nd sample of younger and older participants rated older adults' story quality more positively than that of younger adults, a problematic finding for the inhibitory deficit explanation. Rater age affected ratings of how focused the speech was on the topic, suggesting age differences in criteria for OTS. These findings are consistent with the Pragmatic Change hypothesis, which maintains that older adults adopt communicative goals that emphasize the significance of life experiences rather than conciseness in their personal narratives.

Phonological priming effects on word retrieval and tip-of-the-tongue experiences in young and older adults.

In a repetition priming paradigm, young and older participants read aloud prime words that sometimes shared phonological components with a target word that answered a general knowledge question. In Experiment 1, prior processing of phonologically related words decreased tip-of-the-tongue states (TOTs) and increased correct responses to subsequent questions. In Experiment 2, the priming task occurred only when the participant could not answer the question. Processing phonologically related words increased correct recall, but only when the participant was in a TOT state. Phonological priming effects were age invariant, although older adults produced relatively more TOTs. Results support the transmission deficit model that the weak connections among phonological representations that cause TOTs are strengthened by production of phonologically related words. There was no evidence that phonologically related words block TOT targets.

Open treatment of anterior impingement of the ankle.

We assessed the long-term outcome ofopen debridement for the treatment of anterior impingement of the ankle in 27 patients. By using preoperative radiographs to group patients according to both the McDermott and the van Dijk scoring system, we assessed the accuracy of these classifications in predicting outcome. The Ogilvie-Harris scoring system, a visual analogue scale of patient satisfaction, the time to return to full activities, and the ability to return to sports determined the clinical outcome. Follow-up radiographs were used to assess the recurrence of osteophytes. We also assessed the incidence of talar osteochondral lesions at surgery. At a mean follow-up of 73 years, 23 of 25 patients (92%) without joint-space narrowing had a good or excellent result. Improvement in the Ogilvie-Harris score was seen in all patients. In athletes, 19 of 24 (79%) were able to return to sports at the same level. Two patients with preoperative joint-space narrowing had a poor result. Osteophytes usually recurred and most patients did not feel that the range of dorsiflexion returned to normal, but symptomatic relief allowed most to return to high-level sport. Our results for non-arthritic joints suggest that this is a safe and successful procedure.

Outcome and socioeconomic aspects of suspected child abuse scald burns.

Fifty-two children suffering from abuse-related scald burns were admitted between January 1, 1986, and June 30, 1991. Their clinical and socioeconomic aspects were compared with those of 50 nonabused scalded children. Patients were matched for age, total body surface area burn, and percentage of full-thickness burn. Patient characteristics and initial nutritional parameters were similar except for race; a higher percentage of black children were in the abused group. A significantly longer length of hospital stay was found in the abused children after using analyses of covariance to control for percentages of total and full-thickness body surface area burn. The number of operations and frequency of complications were increased in the abused group, but not significantly so. Several significant differences were found in the socioeconomic characteristics of the two groups. Children suspected of being scalded intentionally were more likely to be part of a broken home, belong to a single parent, and have a younger mother than were children in the control group. The majority of the parents of abused children were unemployed, and all but two earned less than $20,000/year. All but one of the abused children were discharged with a person other than their parents, and compliance with rehabilitation follow-up was significantly worse than with the control group. The person suspected of performing the abuse was always a family member, except in cases where the baby-sitter was the suspected abuser. Child abuse hurts not only the child but also society by increasing the need for resources to pay for extended hospital admissions.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhalation injury severity scoring system: a quantitative method.

Inhalation injury, a major contributor to burn-related mortality, has been difficult to quantify. A scoring system paralleling current adult respiratory distress syndrome systems has the potential to distinguish survivors from nonsurvivors. The utility of the PaO2/FiO2 (P/F) ratio in predicting injury severity was first examined. In a review of 120 patients with inhalation injury, those with P/F ratios greater than or equal to 300 after resuscitation were more likely to survive than those with ratios less than 300. The P/F ratio had no value when obtained before resuscitation. Next, a scoring system was developed to assist in comparing the severity of injury in ventilator-dependent patients with burns. Measurements were recorded prospectively in four categories: chest x-ray evaluation, P/F ratio, peak inspiratory pressure, and bronchoscopy. When comparing survivors (20) versus nonsurvivors (6), significant differences were found early (day 0, day 1, and week 1) for P/F ratio and overall severity score. Differences were seen later (week 1 and week 2) for chest x-ray evaluation and peak inspiratory pressure values. Because of low numbers the value of bronchoscopy could not be evaluated. The role of an inhalation injury severity scoring system for predicting survival should be examined in larger prospective trials.

Left ventricular growth response to exercise and cigarette smoking: data from LARGE Heart.

BACKGROUND: Increasing left ventricular mass is a risk factor for cardiovascular morbidity and mortality. OBJECTIVE: To examine the possible association of smoking with the left ventricular growth response in men. METHODS: Left ventricular mass was measured in 309 army recruits before and after an identical 12-week physical training programme. Left ventricular mass was determined using cardiovascular magnetic resonance. RESULTS: Left ventricular mass increased with training (mean (standard deviation (SD)) 3.83 (10.81) g, p<0.001). By univariate analysis, exercise-induced change in left ventricular mass was positively associated with cigarette smoking (mean (SD) 1.69 (11.10) g v 4.76 (10.23) g for non-smokers v ex- and current smokers, respectively; p = 0.026), whereas age, height, diastolic and systolic blood pressure (SBP), alcohol consumption or indices of physical activity were not significantly associated with change in left ventricular mass. Multivariate analysis showed body weight, smoking status and SBP to be independent predictors of left ventricular mass (incremental R(2) = 3.4%, p = 0.004; R(2) = 4.9%, p = 0.024; and R(2) = 1.7%, p = 0.041, respectively). CONCLUSIONS: Cigarette smoking and SBP are associated with exercise-induced left ventricular growth in young men. The positive association of smoking with changes in left ventricular mass is surprising, given the limited exposure of these subjects to smoking, and although these data do not prove causation, they are of great interest to those trying to uncover the drivers of left ventricular hypertrophy, as well as to those examining the possible ill-effects of smoking in the young.

The significance and clinical factors associated with a subcentimeter resection of colorectal liver metastases.

BACKGROUND: Prognosis after resection of colorectal liver metastases is influenced by various factors. A positive margin of resection (MOR) has been shown to adversely influence prognosis. Although a 1-cm MOR has been accepted as adequate, the data to support this guideline are sparse. METHODS: Our hepatobiliary database was queried for patients who underwent liver resection for colorectal metastases between January 1992 and July 2003. All patients were divided into three groups: MOR <.5 cm (group A), .5 to 1 cm (group B), and >1 cm (group C). Operative reports from each hepatic resection were analyzed to determine local factors that may have contributed to a subcentimeter MOR. RESULTS: A total of 112 patients (67 men and 45 women) underwent liver resection for colorectal metastases with negative margins. Fifty-three patients were in group A, 26 patients were in group B, and 33 patients were in group C. Group C demonstrated decreased local recurrence (LR; P = .003), distant recurrence (DR; P = .008), and disease-free recurrence (P = .002). A significant difference in the overall time to LR (P = .003), time to DR (P = .003), and disease-free survival (P = .002) was also demonstrated. Factors associated with a subcentimeter MOR included nonanatomical resection (P = .043), proximity to a major vessel (P = .003), and central location (P = .002). CONCLUSIONS: A <1-cm resection for colorectal liver metastases is associated with increased LR and DR, as well as decreased disease-free survival. When a nonanatomical resection is performed, a MOR >1 cm should be attempted, because an adequate margin is often underestimated. Considerations should be made for extended resections when tumors are centrally located or near major vessels.

H.M., word knowledge, and aging: support for a new theory of long-term retrograde amnesia.

This study develops a new theory of long-term retrograde amnesia that encompasses episodic and semantic memory, including word knowledge. Under the theory, retrograde amnesia in both normal individuals and hippocampal amnesics reflects transmission deficits caused by aging, nonrecent use of connections, and infrequent use of connections over the life span. However, transmission deficits cause severe and irreversible retrograde amnesia only in amnesics who (unlike normal persons) cannot readily form new connections to replace nonfunctioning ones. The results of this study are consistent with this theory: For low-frequency but not high-frequency words, a famous "hippocampal amnesic" (H.M.) at age 71 performed worse than memory-normal control participants in a lexical decision experiment and a meaning-definition task (e.g., What does squander mean?). Also as predicted, H.M.'s lexical decision performance declined dramatically between ages 57 and 71 for low-frequency words, but was age-invariant for high-frequency words.

Inheritance and RAPD tagging of multiple genes for resistance to net blotch in barley.

A doubled haploid barley (Hordeum vulgare L.) population that was created from a cross between cultivars 'Léger' and 'CI 9831' was characterized by RAPD (random amplified polymorphic DNA) markers for resistance to isolate WRS857 of Pyrenophora teres Drechs. f. sp. maculata Smedeg., the causal agent of the spot form of net blotch. Resistance, which initially appeared to be conferred by a single gene from the approximate 1:1 (resistant : susceptible) segregation ratio of the doubled-haploid (DH) progeny, was found to be associated with three different genomic regions by RAPD analysis. Of 500 RAPD random primers that were screened against the parents, 195 revealed polymorphic bands, seven showed an association to the resistance in bulks, and these seven markers were mapped to three unlinked genomic regions. Two of these regions, one of which was mapped to chromosome 2, have major resistance genes. The third region has some homology to the chromosome 2 region. This study demonstrates the simultaneous location of markers for more than one gene governing a trait by using RAPD and bulked segregant analysis (BSA).

Videotaped materials in a school-based smoking prevention program.

The theory used to frame school-based tobacco use prevention programs is general, and such programs are difficult to replicate. This article seeks to offer a model for prevention videotape production, which other researchers can replicate and improve, and to present an analysis of potential merits and drawbacks of such production. To accomplish these goals, this article presents a detailed description of a school-based prevention program and the videotaped materials used in its curriculum. The theoretical and empirical bases for the project are delineated, and the study design is summarized. A detailed outline of the multi-grade curriculum program is presented, including the rationale behind critical program features, a description of specific curriculum strands, and the way in which videotaped materials fit into each strand. The rationale for using videotaped materials within the theoretical framework is discussed. Each videotape is briefly described. An account of video production, a process extending over 4 years, is set forth, including the student feedback data that helped to shape the production process, formatting, script decisions, casting, location, and the actual filming procedure.

Intracellular glutamine concentration does not decrease in all muscles during sepsis.

The concentrations of glutamine and other amino acids were measured in plasma and intracellular fluid of soleus and extensor digitorum longus (EDL) muscles of rats 4, 8, and 16 hr after induction of sepsis by cecal ligation and puncture or after sham operation. Previous studies have shown that muscle protein breakdown is greatly increased in EDL, but not in soleus muscle, in this sepsis model. Corresponding to previous observations of protein breakdown in sepsis, muscle glutamine was markedly depleted (< 50%) in EDL by sepsis, while no significant fall in glutamine concentration in soleus was observed. Changes in muscle glutamine concentration in sepsis could not be attributed to changes in the precursor of glutamine, glutamic acid. Data were examined for changes consistent with hypothesized alterations in glutamine transport. Correlations among glutamine and other amino acids in muscle, histidine in particular, were consistent with a sepsis-induced alteration in activity of the sarcolemmal glutamine transporter, system Nm. These results thus strengthen the proposed connection between muscle glutamine content and muscle protein metabolism under catabolic conditions.

Comparative evaluation of the oxoid signal and Roche Septi-Chek blood culture systems.

The Oxoid Signal blood culture system (Oxoid USA, Inc., Columbia, Md.) was compared with the Roche Septi-Chek system (Roche Diagnostics, Div. Hoffmann-La Roche Inc., Nutley, N.J.), with the latter consisting of a tryptic soy broth (R-TSB) bottle with an attached agar slide unit and a Columbia broth bottle. A total of 5,034 cultures with equal volumes of blood in each bottle were processed. Overall, more organisms were recovered in the R-TSB bottle than in the Signal bottle, with significantly more aerobic organisms (Pseudomonas spp., Acinetobacter spp., and yeasts) recovered in the R-TSB bottles and anaerobes and viridans group streptococci recovered in Signal bottles. Approximately equivalent numbers of organisms were recovered in the Signal and Columbia broth bottles. The times of detection were essentially identical with the three blood culture broth systems. During the study, 30.6% of the Signal bottles had a positive indicator of growth, of which 1,103 (71.7%) were false-positive cultures. Additionally, nonviable organisms resembling streptococci were observed in 13.7% of the Signal bottles that were Gram stained and in unioculated blood culture bottles. With appropriate modifications of the preparation of the media, the latter problem can be eliminated.

Assessment of 'quality of life' using a daily diary card in a randomised trial of chemotherapy in small-cell lung cancer.

BACKGROUND: Quality of life (QOL) was assessed using a daily diary-card within a multicentre randomised trial of treatment of small-cell lung cancer. The trial compared a weekly dose-intensive regimen with a 3-weekly conventional treatment in good prognosis patients, that is patients with limited disease or extensive disease with a good performance status (ECOG 0or 1) and alkaline phosphatase of less than one and a half times the upper limit of normal. The trial which has been previously reported detected no difference in response or survival. PATIENTS AND METHODS: Daily diary cards (DDCs) were collected for up to eight months from the first day of chemotherapy in a cohort of 75 patients at one centre. Percentages of scores over a specified level were calculated for each of the eight diary card questions and comparisons were made between treatment arms. RESULTS: During the period of chemotherapy compliance in completing DDCs was 72.5% in the weekly arm and 77.2% in the 3 weekly. Significantly worse scores were reported with weekly chemotherapy during this period for six of the eight parameters, namely: ;nausea, vomiting, happiness, appetite, general well-being and sleep. Recognised problems of QOL data collection, in particular, compliance, attrition and generalisability are highlighted by this study and are discussed in the paper. CONCLUSIONS: The QOL measurements indicate that 3 weekly chemotherapy is the preferred treatment. This study demonstrates that QOL measurements may be helpful in choosing between treatment alternatives where no difference in outcome is observed.

A tobacco cryptic constitutive promoter, tCUP, revealed by T-DNA tagging.

We have isolated a constitutive promoter sequence, tCUP, from tobacco by T-DNA tagging using a promoterless GUS-nos3' reporter gene construct. The T-DNA integration event produced a translational fusion with the GUS gene that is expressed widely in organs, at both the mRNA and enzyme activity levels. In tobacco transformed with a tCUP-GUS-nos3' gene, GUS specific activity in leaves was within a range of values similar to those of plants transformed with the widely used constitutive promoter gene fusion, CaMV 35S promoter-GUS-nos3'. Characteristics of the tCUP promoter sequence differ from those of other plant constitutive promoters; for instance, the tCUP sequence lacks a TATA box. Transcription initiates at a single site within the tCUP sequence which is similar to a transcriptional start site consensus sequence determined for plant genes. The tCUP promoter is cryptic as RNA accumulation at the transcriptional start site is not detected in untransformed tobacco. Thus, tCUP is the first example of a cryptic, constitutive promoter isolated from plants. The tCUP-GUS-nos3' gene fusion produced GUS activity in tissues of all species tested suggesting that tCUP may utilize fundamental transcription mechanisms found in plants.

A randomised trial of low-dose/high-frequency chemotherapy as palliative treatment of poor-prognosis small-cell lung cancer: a Cancer research Campaign trial.

We report the results of a randomised trial in extensive small-cell lung cancer (SCLC) of a novel approach to palliative chemotherapy. A widely used 3 weekly regimen was compared with the same drugs given at half the dose but twice the frequency with the same intended overall dose intensity (DI). A total of 167 patients defined as having extensive SCLC with adverse prognostic features were randomised to receive either a 3 weekly regimen of cisplatin 60 mg m-2 i.v. on day 1 and etoposide 120 mg m-2 i.v. on day 1 and 100 mg b.d. orally on days 2 and 3 alternating with cyclophosphamide 600 mg m-2 i.v., doxorubicin 50 mg m-2 i.v. and vincristine 2 mg i.v. all on day 1 for a maximum of six courses (3 weekly); or treatment with the same drugs but with each course consisting of half the 3 weekly dose given every 10 or 11 days for a maximum of 12 courses. In the 10/11 day regimen overall response rate was 58.9% (95% CI, 47.9-69.2%) with 12.8% complete responses (CR). For the 3 weekly treatment the overall response rate was 44.9% (95% CI, 35.0-55.5%) with 10.1% CR. Median survival was similar in the two arms at 6.4 months (95% CI, 4.9-7.3 months) and 5.8 months (95% CI, 4.0-6.6 months) respectively. Survival at 1 year was 9.9% (95% CI, 5.0-18.5%) and 8.9% (95% CI, 4.6-16.6%). The 95% CI for the difference in survival at 1 year is -7.09% to +9.09%. Haematological toxicity and treatment delays owing to infection were more frequent with the 10/11 day regimen but other toxicities were equal in both arms. Other aspects of quality of life were measured in a small representative cohort of patients using a daily diary card (DDC). There was a trend of improved quality of life on the 10/11 day arm, but there was little difference between the two treatments. The trial shows that a low-dose/high-frequency regimen with the same DI as conventionally scheduled chemotherapy gives similar response rates and survival. This and other modifications of the schedule may offer new approaches to palliative treatment of advanced cancer. However, in this trial there was no significant benefit in toxicity or other aspects of quality of life.