Towards an automated data cleaning with deep learning in CRESST.

The CRESST experiment employs cryogenic calorimeters for the sensitive measurement of nuclear recoils induced by dark matter particles. The recorded signals need to undergo a careful cleaning process to avoid wrongly reconstructed recoil energies caused by pile-up and read-out artefacts. We frame this process as a time series classification task and propose to automate it with neural networks. With a data set of over one million labeled records from 68 detectors, recorded between 2013 and 2019 by CRESST, we test the capability of four commonly used neural network architectures to learn the data cleaning task. Our best performing model achieves a balanced accuracy of 0.932 on our test set. We show on an exemplary detector that about half of the wrongly predicted events are in fact wrongly labeled events, and a large share of the remaining ones have a context-dependent ground truth. We furthermore evaluate the recall and selectivity of our classifiers with simulated data. The results confirm that the trained classifiers are well suited for the data cleaning task.

Secular equilibrium assessment in a CaWO4 target crystal from the dark matter experiment CRESST using Bayesian likelihood normalisation.

CRESST is a leading direct detection sub-GeVc-2 dark matter experiment. During its second phase, cryogenic bolometers were used to detect nuclear recoils off the CaWO4 target crystal nuclei. The previously established electromagnetic background model relies on Secular Equilibrium (SE) assumptions. In this work, a validation of SE is attempted by comparing two likelihood-based normalisation results using a recently developed spectral template normalisation method based on Bayesian likelihood. Albeit we find deviations from SE in some cases we conclude that these deviations are artefacts of the fit and that the assumptions of SE is physically meaningful.

Histological and morphometric study of the epididymus of Chinchilla lanigera Grey under controlled conditions in captivity.

Chinchilla lanigera, native to the Andean Mountains of Perú, Chile, Bolivia and Argentina, is a specimen of great economic importance because of its fur. In mammals, spermatozoa originate in testes and are transported to the epididymis, where they undergo morphological and biochemical modifications known as sperm maturation, a basic step in the acquisition of their fertilizing ability. The aim of this work is the macroscopic and microscopic analysis of the epididymis of Chinchilla lanigera Grey and its sectorization based on a histomorphological study. The epididymis presents a clear segmentation into four regions: initial segment, caput, corpus and cauda. The epithelium lining the seminiferous tubules is pseudostratified, with principal cells with stereocilia and basal, clear, apical, narrow and halo cells. The histological analysis showed that principal and basal cells are the prevailing populations in all regions, also revealing narrow cells and the absence of clear cells in the initial segment. Each segment presents its different histological and morphometric characteristics, which supports the idea of the specific behaviour of each region, giving a segment-specific character to the process of sperm maturation in this species. No significant differences were found in the morphometric measurements or in the histological evaluation of the epididymis of samples collected in April and October. The fact that no differences were found between the samples collected during the two periods when the reproductive ability in nature is different suggests the importance of external factors in the control of the reproductive cycle of Chinchilla lanigera.

Models of coronal heating, turbulence and fast reconnection.

Coronal heating is at the origin of the EUV and X-ray emission and mass loss from the sun and many other stars. While different scenarios have been proposed to explain the heating of magnetically confined and open regions of the corona, they must all rely on the transfer, storage and dissipation of the abundant energy present in photospheric motions, which, coupled to magnetic fields, give rise to the complex phenomenology seen at the chromosphere and transition region (i.e. spicules, jets, 'tornadoes'). Here we discuss models and numerical simulations which rely on magnetic fields and electric currents both for energy transfer and for storage in the corona. We will revisit the sources and frequency spectrum of kinetic and electromagnetic energies, the role of boundary conditions, and the routes to small scales required for effective dissipation. Because reconnection in current sheets has been, and still is, one of the most important processes for coronal heating, we will also discuss recent aspects concerning the triggering of reconnection instabilities and the transition to fast reconnection.

Survival of benthic foraminifera under hypoxic conditions: results of an experimental study using the CellTracker Green method.

We present results of an experimental study, in which benthic foraminiferal faunas have been kept under strongly hypoxic conditions. Sixteen short sediment cores from a 35m deep site in the Adriatic Sea were incubated for a maximum of 69days. Some of the cores were air-bubbled and remained well oxygenated throughout the experiment. The other cores were bubbled with nitrogen; the overlying waters of these cores became strongly hypoxic, whereas the sediment remained virtually without oxygen. Live foraminifera have been inventoried with the CellTracker Green method. Our results show that all dominant taxa survive strongly hypoxic conditions. Nouria polymorphinoides and Nonionella turgida show a clear tendency to move to the sediment surface in the nitrogen-bubbled cores, whereas Bulimina spp. and Eggerella scabra do not show such a migrational response. We suggest that this is a response to the concentration of nutritional resources at the sediment-water interface.

A combination of gefitinib and FOLFOX-4 as first-line treatment in advanced colorectal cancer patients. A GISCAD multicentre phase II study including a biological analysis of EGFR overexpression, amplification and NF-kB activation.

Interesting activity has been reported by combining chemotherapy with cetuximab. An alternative approach for blocking EGFR function has been the development of small-molecule inhibitors of tyrosine kinase domain such as gefitinib. We designed a multicentre phase II study in advanced colorectal cancer combining gefitinib+FOLFOX in order to determine the activity and to relate EGFR expression and gene amplification and NF-kB activation to therapeutic results. Patients received FOLFOX-4 regimen plus gefitinib as first-line treatment. Tumour samples were analysed for EGFR protein expression by immunohistochemical analysis and for EGFR gene amplification by fluorescence in situ hybridisation (FISH), chromogenic in situ hybridisation (CISH) and NF-kB activation. Forty-three patients were enrolled into this study; 15 patients experienced a partial response (response rate=34.9%), whereas other 12 (27.9%) had a stable disease. Median progression-free survival (PFS) was 7.8 months and median overall survival (OS) was 13.9 months. We did not find any relationship with EGFR overexpression, gene amplification, while NF-kB activation was associated with a resistance to therapy. Gefitinib does not seem to increase the activity of FOLFOX in advanced colorectal cancer even in patients overexpressing EGFR or with EGFR amplification. Furthermore, while NF-kB activation seems to predict resistance to chemotherapy as demonstrated 'in vitro' models, gefitinib does not overcome this mechanism of resistance, as reported for cetuximab.

Biological predictive factors in rectal cancer treated with preoperative radiotherapy or radiochemotherapy.

We analysed the expression of microsatellite instability, p53, p21, vascular endothelial growth factor and thymidylate synthase (TS) in pretreatment biopsy specimens from 57 locally advanced rectal cancers. The aim of the study was to correlate the expression of these markers with pathological response. Nineteen patients were treated with preoperative concomitant radiotherapy (RT) and fluorouracil/oxaliplatin-based chemotherapy (RCT), while 38 had RT alone. Pathological complete remission (pCR) and microfoci residual tumour (micR) occurred more frequently in patients treated with RCT (P=0.002) and in N0 tumours (P=0.004). Among patients treated with RCT, high TS levels were associated with a higher response rate (pCR+micR; P=0.015). No such correlation was found in the RT group. The other molecular factors were of no predictive value. Multivariate analysis confirmed a significant interaction between nodal status and the probability of achieving a pathological response (P=0.023) and between TS expression and treatment, indicating that a high TS level is predictive of a higher pathological response in the RCT subset (P=0.007). This study shows that lymph node status is the most important predictive factor of tumour response to preoperative treatment. Thymidylate synthase expression assessed immunohistochemically from pretreatment tumour biopsies may be a useful predictive marker of rectal tumour response to preoperative RCT.

Cisplatin, epirubicin, leucovorin and 5-fluorouracil (PELF) is more active than 5-fluorouracil, doxorubicin and methotrexate (FAMTX) in advanced gastric carcinoma.

BACKGROUND: 5-Fluorouracil (5-FU), doxorubicin and methotrexate (FAMTX) and cisplatin, epirubicin, leucovorin and 5-FU (PELF) have both been reported to be superior to the combination 5-FU, doxorubicin and mitomycin C (FAM) in advanced gastric carcinoma. On the basis of the presence and dose intensity of the included agents, we hypothesised that PELF would be superior to FAMTX. PATIENTS AND METHODS: Two hundred patients with untreated advanced gastric carcinoma were randomised to receive PELF or FAMTX for a maximum of six cycles or until disease progression. RESULTS: The complete response (CR) rates to PELF and FAMTX were, respectively, 13% [95% confidence intervals (CI) 6% to 20%] and 2% (95% CI 0% to 5%; P = 0.003), and the objective response rates [CR plus partial response (PR) rates] 39% (95% CI 29% to 49%) and 22% (95% CI 13% to 30%; P = 0.009), thus significantly favouring the PELF combination. The survival rates after 12 months (30.8% versus 22.4%) and 24 months (15.7% versus 9.5%) were also higher among patients receiving PELF, but these differences were not statistically significant. The toxicities were qualitatively different but quantitatively similar. Both regimens seem to be feasible provided that careful patient monitoring is assured. CONCLUSIONS: PELF is significantly more active than FAMTX and deserves further research in the adjuvant setting.

Factors influencing hospital infection control policies in Italian hospitals.

A study was undertaken to determine the resources available in Italian hospitals for the control of nosocomial infections and the factors favouring a successful approach. During January-May 2000 a questionnaire about infection control was sent to the hospital health director of all Italian National Health System hospitals treating acute patients and with more than 3500 admissions in 1999. An active programme was defined as a hospital infection control committee (HICC) meeting at least four times in 1999, the presence of a doctor with infection control responsibilities, a nurse employed in infection control and at least one surveillance activity and one infection control guideline issued or updated in the past two years. There was a response rate of 87.5% (463/529). Almost fifteen percent (69/463) of hospitals had an active programme for Infection Control and 76.2% (353/463) had a HICC. Seventy-one percent (330/463) of the hospitals had a hospital infection control physician and 53% (250/463) had infection control nurses. Fifty-two percent (242/463) reported at least one surveillance activity and 70.8% (328/463) had issued or updated at least one guidance document in the last two years. The presence of regional policies [odds ratio (OR) 8.7], operative groups (OR 4.2), at least one full-time nurse (OR 4.6) and a hospital annual plan which specified infection control (OR 2.1) were statistically associated with an active programme in the multivariate analysis.

Modulation of fluorouracil by methotrexate, leucovorin, and cisplatin (M-FLP) in the treatment of advanced pancreatic cancer: a phase II study of the Italian Oncology Group for Clinical Research (GOIRC).

The objective of this trial was to evaluate the activity and tolerability of biomodulation of 5-fluorouracil by leucovorin, methotrexate, and platinum in patients with advanced measurable disease. Thirty-five patients with histologically or cytologically proven adenocarcinoma of the pancreas were treated with methotrexate (100 mg/m2 in 500 ml 5% dextrose in a 2-hour infusion, day 1), 5-fluorouracil (800 mg/m2/day, i.v. in continuous infusion from days 2 to 5) plus 1-leucovorin (7.5 mg/m2 given per os every 6 hours, from days 2 to 5) and platinum (60 mg/m2 i.v., day 2), every 28 days. Four partial responses (12%; exact 95% confidence interval: 1-23%) were obtained in 34 evaluable patients with a median survival time of 49 weeks (range, 20-77 weeks). Ten (29%) of 34 patients had stable disease. Median time to treatment failure from the beginning of therapy was 11 weeks (range, 4-59 weeks) and median survival time was 20 weeks (range, 4-77 weeks). The most common grade III-IV toxicities were diarrhea (15%), stomatitis (41%), and vomiting (17%). Hematologic toxicity was mild. There were no therapy-related deaths. In conclusion, this trial did not report an increase or improvement in response rate and survival rates, and this regimen cannot be recommended as effective therapy for advanced pancreatic cancer.

Usefulness of latero-orbital electrodes in detecting interictal epileptiform activity--a study of 60 patients with complex partial seizures.

OBJECTIVES: The use of latero-orbital (Lo) electrodes is a routine practice in any EEG laboratory to evaluate eye motion, but there are no data about their usefulness in revealing interictal epileptiform abnormalities. METHODS: In 60 consecutive patients (27 men, 33 women, mean age 36.8 years, range 17-72) with complex partial seizures, we prospectively evaluated the utility of Lo electrodes in comparison with anterior temporal (AT) electrodes, for the detection of interictal epileptiform discharges (SW). RESULTS: No epileptiform abnormality was seen in 4/60 patients. Both AT and Lo electrodes were significantly superior to 10-20 electrodes for detection of both patients and foci. Indeed, the standard 10-20 system alone allowed the detection of only 39 independent epileptiform foci in 35/56 (63%) patients, while AT and Lo electrodes were necessary for detection of 23 epileptiform foci in the remaining 21/56 (37%) patients. Importantly, there was no statistically significant difference in detection between AT and Lo electrodes. CONCLUSIONS: Recordings from Lo electrodes are comparable to those from AT electrodes and are useful for localizing interictal temporal spiking activity. Lo electrodes may be substituted for basal electrodes in the day-to-day evaluation of patients with complex partial seizures.

Cisplatin-gemcitabine combination in advanced non-small-cell lung cancer: a phase II study.

PURPOSE: The nucleoside analog, gemcitabine, has shown activity as a single agent in the treatment of metastatic non-small-cell lung cancer (NSCLC). Its combination with cisplatin in preclinical models suggested synergy between the two drugs. The aim of the study was to evaluate the clinical efficacy and toxicity of the cisplatin-gemcitabine combination in advanced NSCLC. PATIENTS AND METHODS: Forty-eight consecutive previously untreated NSCLC patients entered the trial from January to June 1994. The median age was 60 years (range, 37 to 70) and performance status (PS) was 0 or 1; 22 patients had unresectable stage III disease (21 stage IIIB and one stage IIIA) and 26 had stage IV disease. Gemcitabine 1 g/m2 was administered weekly (days 1, 8, and 15) followed by a 1-week rest and cisplatin 100 mg/m2 on day 2 of each 28-day cycle. Survival and response were determined in accordance with the intention-to-treat principle in all enrolled patients. RESULTS: Of 48 assessable patients, one (stage IV) had a complete response (CR) and 25 achieved a partial response (PR). The overall response rate was 54% (95% confidence interval [CI], 40% to 68%). Thrombocytopenia was the main side effect, with 52% of patients experiencing grade III to IV toxicity, which was usually short-lived and responsible for the omission of gemcitabine administration on day 15 in 50% of chemotherapy courses. The median survival time was 61.5 weeks (95% CI, 40 to 71). CONCLUSION: The combination of gemcitabine and cisplatin induced a high response rate in both stage IIIB and IV NSCLC, with modest side effects. The regimen deserves further careful evaluation in a phase III prospective randomized trial.

Photic-induced epileptic negative myoclonus: a case report.

We present the first documented case of photic-induced epileptic negative myoclonus. A 17-year-old girl had experienced two generalized tonic-clonic seizures (GTCS) while watching television. The only EEG abnormality was a photoparoxysmal response (PPR), which was sometimes accompanied by loss of postural tone in both arms. Valproate was effective in abolishing photosensitivity. Negative myoclonus should be included among the ictal phenomena accompanying PPR.

Glomerular hyperfiltration in essential hypertension: hormonal aspects.

Glomerular hyperfiltration is thought to play a pivotal role in causing renal damage in essential hypertension. An increase in glomerular filtration rate can be experimentally induced by an acute oral protein load through still unclarified mechanisms, although hormonal factors have been postulated; in already hyperfiltering nephrons, the capacity to further increase glomerular filtration rate upon stimulation with an acute protein load (i.e. renal functional reserve) would conceivably be reduced, even in the presence of apparently normal renal function. The present study aimed at assessing whether renal functional reserve is preserved and/or is affected by different antihypertensive drugs in essential hypertensive patients without signs of renal function impairment; moreover, we tried to highlight changes in the plasma levels of natriuretic and antinatriuretic hormones potentially involved in the modulation of renal hemodynamics under the chosen experimental conditions. Renal hemodynamic parameters, plasma renin activity, aldosterone and atrial natriuretic factor were measured in fourteen essential hypertensives submitted to an acute oral protein load, alone or with a concomitant administration of either nifedipine or enalapril, as compared with a control carbohydrate meal. Glomerula filtration rate and renal plasma flow rose slightly but not significantly following an acute oral protein load as compared with a carbohydrate meal; no changes were noted in plasma atrial natriuretic factor levels, whereas plasma renin activity decreased. When nifedipine was administered together with the protein meal, both glomerular filtration rate and renal plasma flow increased significantly; there were also, parallel increases in plasma renin activity and atrial natriuretic factor. Administration of enalapril was associated with a decrease in both glomerular filtration rate and renal plasma flow; plasma renin activity showed an expected marked rise, whereas the plasma levels of atrial natriuretic factor were only slightly but not significantly reduced and plasma aldosterone fell. In conclusion, our data suggest that in our patients renal functional reserve was blunted. Clear-cut hyperfiltration was brought about by administration of nifedipine together with a protein meal, whereas enalapril completely abolished even the small increase in glomerular filtration rate seen after protein meal alone. The concomitant alterations in plasma renin activity, aldosterone and atrial natriuretic factor seemed to play no major role in the determinism of the observed renal hemodynamic changes.

Physiological stimuli to atrial natriuretic peptide secretion in normal humans.

We tested the response of plasma atrial natriuretic peptide (ANP) levels to the following physiological stimuli: postural changes; head-out water immersion; and physical exercise. Plasma ANP (p-ANP) levels were assessed by a specific, sensitive radio-immunoassay. Plasma ANP rose significantly when posture shifted from upright to recumbent for 1 h, but fell again to basal values after 10 min standing. Circadian variations did not affect the posture study. Head-out water immersion produced a prompt and remarkable (sevenfold) increase in p-ANP, with a plateau reached after 1 h and held until the end of the experiment (2 h). Plasma ANP levels were measured in 10 normal subjects performing supine treadmill exercise at 50% of maximum aerobic capacity for 30 min. Plasma ANP rose from baseline supine values after 15 min exercise, and remained elevated during the following 15 min exercise. During the recovery phase ANP showed a trend towards baseline values, with a 38% decrease attained after 30 min. We propose that the above tests could be used as ANP-stimulating manoeuvres in physiological and clinical conditions in man.

[Diagnostic accuracy of double contrast examination in the detection of gastric polyps (author's transl)]. / Misura della accuratezza diagnostica dell'esame radiologico a doppio contrasto nel riscontro dei polipi gastrici.

Gastric polyps have been found in 2.9% of 4322 consecutive routine double contrast examination of upper gastro-intestinal tract. In 559 patients, endoscopically verified, sensitivity of radiological test was 96% and specificity 96.3%. An agreement index (K-index) was evaluated in a sample of 84 cases. The index value was 0.9 among 2 different radiologists with a similar, high experience and 0.8 among 2 radiologists with different degree of experience in double contrast examination. Our results demonstrate the validity of the double contrast study of the stomach as preliminary to endoscopy.