How do climate change experiments alter plot-scale climate?

To understand and forecast biological responses to climate change, scientists frequently use field experiments that alter temperature and precipitation. Climate manipulations can manifest in complex ways, however, challenging interpretations of biological responses. We reviewed publications to compile a database of daily plot-scale climate data from 15 active-warming experiments. We find that the common practices of analysing treatments as mean or categorical changes (e.g. warmed vs. unwarmed) masks important variation in treatment effects over space and time. Our synthesis showed that measured mean warming, in plots with the same target warming within a study, differed by up to 1.6  ∘ C (63% of target), on average, across six studies with blocked designs. Variation was high across sites and designs: for example, plots differed by 1.1  ∘ C (47% of target) on average, for infrared studies with feedback control (n = 3) vs. by 2.2  ∘ C (80% of target) on average for infrared with constant wattage designs (n = 2). Warming treatments produce non-temperature effects as well, such as soil drying. The combination of these direct and indirect effects is complex and can have important biological consequences. With a case study of plant phenology across five experiments in our database, we show how accounting for drier soils with warming tripled the estimated sensitivity of budburst to temperature. We provide recommendations for future analyses, experimental design, and data sharing to improve our mechanistic understanding from climate change experiments, and thus their utility to accurately forecast species' responses.

The role of cetuximab in pre-treated refractory patients with metastatic colorectal cancer: outcome study in clinical practice.

We carried out a multicentric retrospective study on cetuximab + chemotherapy in pre-treated refractory patients outside clinical protocols, by registering the main clinical and pathological parameters. We evaluated 144 pre-treated patients. Cetuximab was administered usually in combination with irinotecan (93.8%). A 45% disease control rate (complete plus partial responses plus stable disease) was obtained in 55 patients and was related to absence of weight loss (p<0.0001) and high grade (> or =2) skin toxicity (p<0.0001). Median time to progression (TTP) was 4 months (95%CI 2.7-5.3) and median overall survival (OS) was 11.8 months (95%CI 8.5-15.1). Performance status << or =1, no weight loss and high grade (>or =22) skin toxicity were related both to a longer TTP (p=0.035, p=0.035, p=0.0017) and OS (p<0.0001, p<0.0001, p=0.006). According to multivariate analysis, the absence of weight loss was related to longer TTP (HR 0.331, p=0.004) and OS (HR 0.176, p<0.0001), and EGFR over-expression (3+) to longer TTP (HR 0.402, p=0.020).

Eight isolated cases of KBG syndrome: a new hypothesis of study.

We report on eight cases of patients affected by KBG syndrome (KBG stands for the initials of the affected patients in the original report), a rare genetic disease, that we find only in 40 cases mentioned in the scientific literature. In this work we present the minimum diagnostic criteria of diagnosis due to identify the syndrome and a hypothesis of study for the research of the involved factors.

Role of radiography and ultrasonography in the diagnosis of the pediatric gastro-esophageal reflux disease.

Twenty-four hour esophageal pH-monitoring is gold standard for evaluate pathological GERD. Role of radiography and ultrasonography in the diagnosis of gastro-esophageal reflux disease (GERD) has been studied. Our results have been shown that radiography and ultrasonography have a limited role in the diagnosis of pathological GERD. However, such investigations an useful the follow-up of patients affected by pathological GERD.

Neoadjuvant chemotherapy in cervical carcinoma: regulators of cell cycle, apoptosis, and proliferation as determinants of response to therapy and disease outcome.

To evaluate whether cellular markers predict the responsiveness to neoadjuvant chemotherapy (NAC) in cervical cancer, 21 patients with stages I and II cervical carcinomas treated by NAC before surgery were followed up for a mean of 52.3 months. Pre-NAC biopsy and operative specimens were subjected to counting of apoptotic (AI/V) and mitotic (MI/V) indices, detection of human papillomavirus (HPV) DNA, and immunohistochemical analysis of cell cycle and proliferation markers (p21, p53, pRb, proliferating cell nuclear antigen [PCNA], Ki-67) and multidrug resistance gene (MDR1), as related to NAC response (RAC), recurrence-free (RFS), and overall (OS) survival. Adenosquamous histology and lymph node involvement were significant determinants of nonsurvival. All carcinomas contained HPV DNA. In univariate analysis, p21, pRb, and MDRI in the biopsy specimen and PCNA, Ki-67, and pRb in the surgical sample significantly predicted RAC, while age, AI/V number of lymph nodes removed, and MI/V predicted RFS. Highly significant predictors of OS were AI/V number of lymph nodes removed, post-NAC MDR1 expression, MI/V and recurrence. Multivariate analysis confirmed the strong post-NAC effects of histologic type, AI/V, and MDR1 expression for RFS, and recurrence, age, and Ki-67 expression for OS. NAC responders with slightly decreased AI/V and increased MI/V had a poor prognosis.

Pilot study on induction chemotherapy with cisplatin, epirubicin, etoposide and bleomycin in cervical cancer stage Ib, IIa and IIb.

METHODS: Induction chemotherapy, consisting of 3 courses of cisplatin (30 mg/m2/i.v. 1st and 2nd day), epirubicin (30 mg/m2/i.v. 1st and 2nd day), etoposide (75 mg/m2/i.v. 1st and 2nd day) and bleomycin (15 mg/i.v. 1st and 2nd day), prior to radical hysterectomy and lymph nodes resection, was used in the primary treatment of 34 consecutive patients (pts) with cervical carcinoma: 8 stage Ib < 4 cm, 11 stage Ib > 4 cm, 13 stage IIa, 2 stage IIb. Median age was 55 years (range 32-75) and median Karnofsky performance status was 90% (range 70-100%). RESULTS: Among the 34 evaluable patients (pts), the overall clinical response rate was 53%, which included a complete response in 9 pts (26.5%) and a partial response in 9 subjects (26.5%). Fifteen stable diseases and one progression were also observed. All the pts were operated on and no invasive residual tumor was found in the surgical specimens obtained from 6/9 clinical complete responders. Lymph-node metastases were found after chemotherapy in 16% (5/32) of the pts with stable disease. Eight pts presented disease recurrence, four had isolated pelvic recurrences, two had pelvic and distant failure, and two had isolated distant metastases. Until now, 9 pts have died. The most frequent toxic effects were: alopecia 100%, nausea-vomiting 73% (25/34), leukopenia 65% (22/34). CONCLUSION: The results suggest that the administration of induction chemotherapy prior to surgery is effective in reducing the tumor volume and results in tolerable toxicity. However, the impact on survival is questionable and randomized trials for conventional treatment are needed.

Hospital-at-Home for advanced cancer patients within the framework of the Bologna Eubiosia project: an evaluation.

AIMS AND BACKGROUND: An evaluation of the Bologna Hospital-at-Home (BHH) was undertaken to examine the following aspects: 1) median daily costs of the BHH; 2) delivery of medical services; 3) patient satisfaction with the care received and frequency of requests for transfer to the alternative setting. Delivery of services and patient's satisfaction in the BHH were compared with data collected for a traditional hospital (Ospedale Sant'Orsola Malpighi, Bologna--OSM). METHODS: Our analysis was performed as a cost analysis considering two periods of time in 1992 and 1993/94. Included were direct and indirect costs; no intangible costs were found. The patient's perspective was selected for the analysis. The observational study examining delivery of service and quality of life of patients admitted to the two care settings, BHH and OSM, considered patient's clinical history and an interview conducted by the evaluation team 6 weeks after admission to either facility. Data included patient's characteristics, quantity of diagnostic and therapeutic measures, circumstances of life, satisfaction with the care received, and intention for transfer to the alternative setting of nursing. The statistical significance of our assumption of comparable care intensity and better patient quality of life in the BHH was tested by the Pearson Chi-square test. RESULTS: A survey was carried out of 236 patients treated in the BHH or the OSM. The setting of assistance did not influence the provision of services. The time of "talking to the doctor" was notably higher for BHH than for OSM patients. The analysis of satisfaction showed that 98% of the surveyed BHH patients believed it matched the actual needs. The quality of life was considered to be reduced/bad in 67% of the OSM patients but in only 51% of BHH patients. An opinion was also requested with regard to transfer to the alternative setting of nursing: 47% of OSM patients judged BHH care would be better than traditional hospital. The median daily costs in BHH reached 118,789 Lire (range, 108,569-129,027 Lire, depending on performance status). CONCLUSIONS: Although the economic advantage of hospital-at-home care certainly is important, we would like to stress that better quality and dignity of life should be the main point supporting the idea of hospital-at-home care.

[Home hospital for advanced stage cancer patients: costs and benefits]. / Homehospital für Krebskranke im fortgeschrittenen Stadium: Kosten und Nutzen.

15,290 patients have been treated in the Bologna home hospital (BHH) until June 30, 1996. The average daily costs in BHH were estimated as 118789 Liras (ranging from 108 569-129027 Lire depending on the nursing category). Care intensity and patient's quality of life in the BHH are high. 98% of patients were content with the setting in which they were nursed. A questionnaire on the degree of satisfaction with the care was completed by 134 BHH patients and 102 patients of Division Oncologia Medica. Azienda Ospedaliera Sant, Orsola Malpighi, Bologna. Satisfaction with respect to sleeping, meals and family communications was expressed more often by BHH patients. Less patients of the BHH evaluated "quality of life" reduced or bad (51% vs. 67%) or requested a transfer to the alternative setting (03% vs. 47%). Advocating step by step introduction of home care, quality of life aspects have priority. Certainly, home care deserves greatest attention providing care during the life with cancer. However the final decision about the settings of nursing has to be made by the patients themselves in accordance with his understanding of quality of life.

Combined chemo-immuno-hormonotherapy of advanced renal cell carcinoma.

Thirty-five patients (pts.) with advanced renal cell carcinoma were treated with a combination of vinblastine (5 mg/m2/IV) plus epirubicin (50 mg/m2/IV) every 3-4 weeks, alpha-2-A-interferon (9 x 10(6) U/IM 3 times in the 1st week, then 18 x 10(6) U/IM 3 times weekly), and medroxyprogesterone acetate (2,000 mg/os/day plus 500 mg IM/week). Thirty-one patients were males and 4 were females with a median age of 63 years (range 35-75) and median performance status of 70% (range 50-90%). We observed nine partial remissions (26%) with median duration of 40 weeks (range 20-232+). Fifteen pts. had no change (43%) while 11 pts. progressed (31%). The main side-effects were: leukopenia (29/35, 83%) with median nadir of 3,100 WBC/mm3 (range 510-3,990) and fever (32/35, 91%). Thrombocytopenia occurred in 4 pts. (11%), anemia in 5 (14%), asthenia in 12 (34%), nausea/vomiting in 12 (34%), alopecia in 8 (23%) and stomatitis in 3 (8.5%). Two patients stopped the therapy with medroxyprogesterone acetate because of muscular cramps. Median survival was 65 weeks (range 6-327+). We conclude that the combination of recombinant alpha 2A-interferon-vinblastine-epirubicin and medroxyprogesterone acetate has modest but definitive activity in patients with advanced renal cell carcinoma.

A phase II study of carboplatin and cyclophosphamide in advanced ovarian carcinoma.

Forty-two patients affected by either stage III and IV ovarian cancer with residual tumor after surgery or recurrent ovarian cancer entered a phase II study of the combination carboplatin 300 mg/m2 and cyclophosphamide 600 mg/m2 every 28 days. Thirty-eight patients were evaluable for response and of these 27 obtained complete or partial remission with a 71% overall remission (clinical complete remission 45%; partial remission 26%). Treatment tolerability was on the whole good. The most frequent side effects were leukopenia (76%), anemia (67%) and nausea/vomiting (60%). Thrombocytopenia was present in 31% of the patients, but nearly always to a mild degree except for one grade 4 case. No other grade 4 side effect was observed. We did not observe any cases of nephrotoxicity and only two patients complained of paresthesia. This carboplatin-cyclophosphamide combination in advanced ovarian carcinoma produces comparable results, in terms of objective responses, to those obtained with standard cisplatin-based regimens, with suggestion of a better toxicological profile.

Platelet synthesis of cyclooxygenase and lipoxygenase products in type I and type II diabetes.

In 24 type I and 22 type II diabetic patients without vascular complications and in 25 controls platelet thromboxane A2 (TxA2) and prostaglandin E2 (PGE2) production (by radioimmunoassay-RIA) and 1-14C arachidonic acid (AA) metabolism (by high pressure liquid chromatography-HPLC) after thrombin stimulation were studied. Platelets both from type I and type II diabetics generated larger amounts of TxB2 (p less than 0.001) and PGE2 (p less than 0.005) than controls, independently of the presence of retinopathy. No significant differences in platelet AA uptake or metabolism via the cyclooxygenase (CO) route, after thrombin stimulation (5 NIH U/ml), were observed in diabetic patients: lipoxygenase metabolites were found to be slightly, but significantly decreased. A positive linear relationship (r = 0.64, p less than 0.001) was found between HbA-1c and TxB2 production, but not with fasting plasma glucose. These results indicate that metabolic alterations can affect platelet function independently of vascular complications. The absence of alterations in intraplatelet 1-14C AA metabolism via CO, in the presence of increased TxB2 and PGE2 production from endogenous AA, suggests that the activation of CO is not the only possible mechanism of platelet activation and that probably an increased availability of platelet AA plays an important role in the enhanced platelet aggregation commonly found in diabetics.

Altered intraplatelet arachidonic acid metabolism during the acute state of unstable angina.

Thromboxane A2 (TxA2) generation and 1-14C arachidonic acid (AA) metabolism by platelets (stimulated with thrombin) were studied in vitro in 16 patients with unstable angina both during the acute and chronic inactive phase of the angina. Eight patients with stable effort angina and 21 controls were also investigated. In acute unstable angina 1-14C AA metabolism was significantly increased through cyclooxygenase pathway resulting in a higher selective TxA2 generation than in stable effort angina and in controls (p less than 0.01). No differences were found between patients with stable effort angina and controls. The alterations in AA metabolism were no longer found when patients reverted to the inactive phase of angina. TxA2 generation by platelets was independent of the number of the daily ischemic attacks (r = 0.17, ns) in patients with unstable angina. Present results indicate that an altered intraplatelet AA metabolism leading to the increased TxA2 synthesis occurs simultaneously with the conversion of angina from the chronic to the acute phase.

Altered 1-14C arachidonic acid metabolism in arterial wall from patients with renal cell carcinoma.

The metabolism of 1-14C arachidonic acid (AA) by arterial wall in patients with renal cell carcinoma and in control patients undergoing nephrectomy was investigated by a high pressure liquid chromatography (HPLC) system. No differences in 1-14C AA uptake and in the total amount of metabolites were found between the two groups, whereas the amounts of cyclooxygenase and lipoxygenase pathway (COP and LOP) metabolites produced by patients with renal cell carcinoma were significantly lower and, respectively, higher than those produced by the control group. The COP/LOP ratio was 7.2 +/- 5.5 in the control group in comparison to 1.9 +/- 0.5 in renal cell carcinoma patients. The decrease in COP metabolites was due to a markedly reduced synthesis of prostacyclin (PGI2), with no changes in thromboxane B2 (TxB2), prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E2 (PGE2) production. The changes in PGI2 and 12-hydroxy-eicosatetraenoic acid (12-HETE) (metabolite of LOP) vascular production were not related to tumor dimension. The decrease in PGI2 synthesis may represent a factor favoring metastasis and thrombosis in neoplastic patients.

TxA2 production by human arteries and veins.

Human arterial and venous segments from patients under-going operations when incubated in Tris buffer both alone and with arachidonic acid were able to produce thromboxane B2 (assessed by radioimmunoassay). Thromboxane B2 (TxB2) production was progressive in time (till 40 min.) and was enhanced by the addition of 1mM norepinephrine. Contamination of tissues by platelet was checked and platelets did not contribute to thromboxane formation. The investigation of the conversion of 1-14C arachidonic acid by vascular tissue indicated that human vascular tissues produce the metabolites of the cyclooxygenase dependent pathway and that prostacyclin is the main metabolite with a PGI2/TxA2 ratio of 4:1. The arterial wall was found to possess an active lipoxygenase dependent pathway. Thromboxane production by intimal cells was negligible and the main source of thromboxane was the media. The production of thromboxane did not change in relation to age, but arterial segments from men produced significantly larger amounts of thromboxane than those from women.