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Background: Squamous Cell Carcinoma of the Head and Neck (SCCHN) are neoplasms arising from the epithelium of the first aero-digestive tract. They are very heterogeneous both clinically and biologically. Classic and well acknowledged risk factors are alcohol and tobacco consumption and other forms of smokeless tobacco assumption, although lately the incidence of Human Papilloma Virus (HPV)-related SCCHN is rapidly increasing. HPV-related tumors are very different from their alcohol and tobacco-associated counterpart, as they show strong chemo and radio sensitivity and thus can often be treated with conservative treatment strategies. Moreover, peculiar biologic features characterize HPV-related tumors, such as wild type TP53, low expression of Epidermal Growth Factor Receptor (EGFR), wild type CCND1 and high expression of P16. In contrast, alcohol and tobacco related SCCHN show opposite features, together with higher number of chromosomal and genetic abnormalities, conferring them chemo and radio resistance. Methods: We have performed a narrative review of the PubMed database with the aim to study the mutational landscape of SCCHN. Results: Several lines of evidence support the existence of at least two genetically different types of SCCHN, one virus-related and the other alcohol and/or tobacco-related, characterized by both clinical and biological opposite features. Virus related SCCHN are very chemo and radiosensitive, so suitable for organ preserving strategy, which in the near future may be induction chemotherapy followed by association of chemotherapy and underpowered radiotherapy. Alcohol and tobacco related SCCHN are themselves strongly heterogeneous and can be divided in different entities on the basis of the “Driver” genetic aberration, responsible for carcinogenesis. The most frequently mutated genes in alcohol and tobacco-related SCCHN are TP53, NOTCH1, CCND1, CDKN2A, EGFR and PI3KCA. Conclusions: Virus-related SCCHN can be managed with chemo-radiotherapy. Alcohol and tobacco-related tumors should be further characterized on the basis of their “Driver Mutations” in order to select effective targeted therapies.

Typologic study and chemistry of zircon populations from Middle Triassic-Lower Liassic arenitic continental redbeds of the Internal Domains successions of the Mediterranean chains, from the Gibraltar Arc to the Calabria-Peloritani Arc, allow assessment of whether this type of study may be used to obtain more comprehensive inferences on the sedimentary evolution of ancient clastic rocks. Calabria-Peloritani Arc zircons are primarily euhedral, with subordinate rounded and subrounded grains. Rifian Maghrebides samples contain abundant euhedral zircons, with minor rounded and ovoid zircons. Betic Cordillera zircons are rounded or subrounded, with minor euhedral elongate grains; rounded zircons of these samples cannot be typologically classified. Electron-microprobe analyses (Si, Zr, Hf, P, and HREE) indicate homogeneous compositions, suggestive of common source areas characterized by granitoid rocks, whereas typology suggests the existence of two distinct groups. The first group includes arenites from the Calabria-Peloritani Arc and the Rifian Maghrebides. The second group includes arenites from the Betic Cordillera. Differences between the two zircon groups may be related to recycling effects, in agreement with a geochemical study of Triassic to lowermost Jurassic mudrock redbeds. Recycling likely was more significant for the Betic Cordillera samples. These results suggest that zircon typology and mudrock geochemistry can be useful tools for provenance, especially in complex sedimentary contexts where arenite-mudrock couplets occur.

Antibiotic resistances and level of acid inhibition may affect the outcome of eradicating regimens for H. pylori. To evaluate the impact of different degrees of acid inhibition on the efficacy of triple treatment, we treated 323 patients with H. pylori infection with clarithromycin and tinidazole plus omeprazole, either 20 mg bid or 40 mg bid. Gastric biopsies and antimicrobial susceptibility testing were performed. Eradication was evaluated by means of breath test. Eradication rates were (intention to treat and per protocol) 83.3 and 84.3% in patients receiving 40 mg omeprazole and 81.9 and 84.1% in those receiving 80 mg omeprazole. Culture was successful in 218 patients (68.7%). Resistance to clarithromycin and metronidazole were found in 13.7 and 20.6%, respectively. Eighteen further patients (8.2%) presented double resistance. Resistance was comparable across the two groups. In resistant patients the eradication rate was significantly lower (66.6% [95% CI, 56–76%], vs 86% [95% CI, 78–91%]; P = 0.001). Antibiotic resistance (OR, 2.73; 95% CI, 1.4–5.3) and smoking (OR, 2.68; 95% CI, 1.4–5.2) were independent predictors of eradication failure. Omeprazole, 20 mg bid, achieves the optimal acid inhibition in H. pylori eradication. Increasing antisecretory activity does not significantly enhance cure rates.

Background & Aims: It still is debated whether post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis can be prevented by administering either somatostatin or gabexate mesylate. The aim of the study is to assess the efficacy of a 6.5-hour infusion of somatostatin or gabexate mesylate in preventing ERCP-related complications. Methods: In a double-blind multicenter trial, 1127 patients undergoing ERCP were randomly assigned to intravenous administration of somatostatin (750 @mg; n = 351), gabexate mesylate (500 mg; n = 381), or placebo (saline; n = 395). The drug infusion started 30 minutes before and continued for 6 hours after endoscopy. Patients were evaluated clinically, and serum amylase levels were determined at 4, 24, and 48 hours after endoscopy. Results: No significant differences in incidences of pancreatitis, hyperamylasemia, or abdominal pain were observed among the placebo (4.8%, 32.6%, and 5.3%, respectively), somatostatin (6.3%, 26.8%, and 5.1%, respectively), and gabexate mesylate groups (5.8%, 31.5%, and 6.3%, respectively). Univariate analysis of patient characteristics and endoscopic maneuvers showed that a Freeman score >1 (P < 0.0001), >=3 pancreatic injections (P < 0.00001), and precut sphincterotomy (P = 0.01) were significantly associated with post-ERCP pancreatitis. At multiple logistic regression analysis, >=3 pancreatic injections (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.45-2.63) and a Freeman score >1 (OR, 1.47; 95% CI, 1.11-1.94) retained their predictive power. Conclusions: Long-term (6.5-hr) administration of either somatostatin or gabexate mesylate is ineffective for the prevention of post-ERCP pancreatitis. Pancreatic injury seems to be related to difficulty in common bile duct access.

BACKGROUND & AIMS: Intrasphincteric injection of botulinum toxin has been suggested as an alternative treatment modality in esophageal achalasia. A controlled trial comparing botulinum toxin, placebo, and pneumatic dilation is reported. METHODS: Sixteen patients received random intrasphincteric injections of either botulinum toxin or saline. The efficacy of treatment was assessed by symptom score, esophageal manometry, and scintigraphy. In case of failure, pneumatic dilation was performed. RESULTS: One month after injection, symptoms had improved in all patients treated with botulinum toxin (symptom score, 0.9 +/- 0.6 vs. 5.5 +/- 1.4; P < 0.02). In the placebo group, symptoms were unchanged in all patients, who were all dilated. Lower esophageal sphincter pressure decreased by 49% after treatment with botulinum toxin (P < 0.03) and by 72% after dilation (P < 0.01). Similarly, esophageal retention decreased by 47% after treatment with botulinum toxin (P < 0.02) and by 59% after dilation (P < 0.02). No significant difference in symptom score and esophageal function test results was found between patients treated with botulinum toxin injections and those undergoing dilation. However, 7 of the 8 patients in the botulinum toxin group required a second injection because of recurrent dysphagia. CONCLUSIONS: Treatment of achalasia with botulinum toxin was as effective as pneumatic dilation in relieving symptoms and improving esophageal function. The effect of the first injection was temporary, but the effect of the second injection lasted longer. (Gastroenterology 1996 Dec;111(6):1418-24)

Early endoscopic diagnosis improves the prognosis of patients with gastric cancer, as shown by the finding that 5-year survival rates exceeding 90% are observed in Japanese patients with early gastric cancer. It has been hypothesized between minute, small, and large early gastric cancers has been proposed. The aim of this study was to determine the prevalence of minute and small early gastric cancers in Western countries and to compare their clinicopathologic features with those of large early gastric cancers. Of 465 Italian patients with gastric cancer who were studied, 20.5% had an early gastric cancer, and 34.7% of these were minute or small. Tumor size is correlated with intramural spreading and metastasis to perigastric lymph nodes. Nodal involvement occurs more frequently in the diffuse than in the intestinal type of early gastric cancer. Long-term survival rate is not coreelated with tumor size, intramural spreading, or nodal metastasis. The minute and small early gastric cancers of Italian patients are indistinguishable from those occurring in Japanese patients. These lesions are more common than previously thought and should be carefully searched for endoscopists. The correlationo of tumor size with intramural invasion and perigastric lymph node metastasis suggests that minute and small early gastric cancers are precursors of large early gastric cancers. Although the distinction between minute, small, and large early gastric cancers is of low prognostic value, the distinction might be useful for selecting different therapeutic approaches.

It is thought that Helicobacter pylori infection may influence growth rate in children. The aim of this study was to evaluate the prevalence of H pylori infection in healthy Italian children, and to look for differences in height between infected and non-infected subjects. Two hundred and sixteen children, aged 3 to 14 years, were tested for H pylori infection by ¹³C-urea breath test. Centile values for height were calculated. Composite indices for socioeconomic class and household crowding were also determined. Forty nine of 216 children (22.7%) were H pylori positive. The prevalence of infection increased with age. Eight of 49 H pylori positive children (16.3%) were below the 25th centile for height, compared with 13 of 167 H pylori negative children (7.8%). This difference became significant in children aged 8.5 to 14 years; in this group (n = 127), eight of 31 infected children (25.8%) were below the 25th centile for height, compared with eight of 96 non-infected children (8.3%). A significant correlation was found between socioeconomic conditions, household crowding, and H pylori status. By using stepwise logistic regression, only the centile value for height was significantly related to H pylori status in older children. Thus H pylori infection was associated with growth delay in older children, poor socioeconomic conditions, and household overcrowding. This finding is consistent with the hypothesis that H pylori infection is one of the environmental factors capable of affecting growth.

GASTROENTEROLOGY 1998;114:857-858

The relationship between arterial hypertension cardiovascular and cerebrovascular events are well-known as well as to target-organ damage. It is not yet definitively clear whether white-coat hypertension (WC-HT) constitutes a risk factor. We have studied the relationship between WC-HT and target-organ damage in 60 subjects (32 M, 28 F; mean age 64±5.2). WC-HT was defined when clinical blood pressure>140/90 mmHg and average daytime ambulatory blood pressure (30 pts) or home blood pressure (30 pts) =120/80 mmHg. Target-organ damage was assessed using the left ventricular mass index (LVMI) measured by echocardiography; the thickness of the intima-media complex (IMT) measured at the common carotid 1 centimetre from the flow-divider; diameter of abdominal aorta determined by echography; ventricular arrhythmias (couplets, ventricular tachycardia and R-on-T phenomena) by dynamic ECG; presence of hypertensive retinopathy. Patients smokers and/or with diabetes mellitus, hyperlipidemia, history of coronary disease, cerebrovascular disease, peripheral arterial disease, were excluded from the study. All patients were examined at the beginning of the study and after 24 months. Results: data refers to 55 subjects. 5 subjects, all by home blood pressure, developed arterial hypertension. The left ventricular mass was tested in 40 patients who had a good quality echocardiogram. The diameter of the abdominal aorta was measured in 58 subjects. In the two-year follow-up there were no non cardiovascular and/or cerebrovascular events. Conclusions: 1) white-coat hypertension does not constitute a risk factor in the development of target-organ disease and/or cerebrovascular and cardiovascular events. 2) However, it is necessary to keep checking white-coat hypertension subjects because they could develop arterial hypertension. 3) ABPM is the more reliable method compared to home blood pressure.(See Table) BasalAfter 24 monthsClinical Blood Pressure160/97 mmHg156/93 mmHgAverage Daytime/Home Blood Pressure118/79 mmHg120/80 mmHgLVMI90±15 gr/mq95 ± 18 gr/mqAbdominal Aorta21 ± 2 mm22 ± 3 mmIMT0.78 ± 0.04 mm0.80 ± 0.05 mmSubjects with Complex Arrythmias21Subjects with Retinopathy00

The softmax function is widely used in deep neural networks (DNNs), its hardware performance plays an important role in the training and inference of DNN accelerators. However, due to the complexity of the traditional softmax, the existing hardware architectures are resource-consuming or have low precision. In order to address the challenges, we study a base-2 softmax function in terms of its suitability for neural network training and efficient hardware implementation. Compared to the classical base- $e$ softmax function, the base-2 softmax function is a new softmax function that uses 2 as the exponential base instead of $e$. From the aspects of mathematical derivation and software simulation, we first demonstrate the feasibility and good accuracy of the base-2 softmax function in the application of neural network training. Then, we use the symmetric-mapping lookup table (SM-LUT) method to design a low-complexity architecture but with high precision to implement it. Under TSMC 28nm CMOS technology, an example design of our architecture has the area of $5676 ~\mu m^{2}$ and the power consumption of 13.12 mW for circuit synthesis at the frequency of 3 GHz. Compared with the latest works, our architecture achieves the best performance and efficiency. [ABSTRACT FROM AUTHOR]

GPUs became the reference platform for both training and inference phases of Convolutional Neural Networks (CNN) due to their tailored architecture to the CNN operators. However, GPUs are power-hungry architectures. A path to enable the deployment of CNNs in energy-constrained devices is adopting hardware accelerators for the inference phase. The design space exploration of CNNs using standard approaches, such as RTL, is limited due to their complexity. Thus, designers need frameworks enabling design space exploration that delivers accurate hardware estimation metrics to deploy CNNs. This work proposes a framework to explore CNNs design space, providing power, performance, and area (PPA) estimations. The heart of the framework is a system simulator. The system simulator front-end is TensorFlow, and the back-end is performance estimations obtained from the physical synthesis of hardware accelerators, not only from components like multipliers and adders. The first set of results evaluate the CNN accuracy using integer quantization, the accelerators PPA after physical synthesis, and the benefits of using a system simulator. These results allow a rich design space exploration, enabling selecting the best set of CNN parameters to meet the design constraints. [ABSTRACT FROM AUTHOR]

A marine-continental transition Tertiary-age succession from the Sorbas Member in the Sorbas Basin (SE Spain) is described. Deposition commenced with nearshore shelf/tidal channel sediments, which were subsequently overlain by lagoonal sediments and capped by a dune field. Within the lagoonal sediments a range of mammal and bird ichnofossils were noted. The bird tracks represent a typical shoreline assemblage, including waders (Antarctichnus fuenzalidae). The mammal ichnofossils include a gazelle (Pecoripeda (Gazellipeda) gazella), but more importantly, a jackal-like predator (Canipeda longigriffa). Jackals have, to date, not been described from this area. Indeed, the oldest representative of the Canidae occurs in the late Miocene, with direct evidence of jackals only in the Plio-Pleistocene. This ichnofossil, therefore, would appear to extend the range of jackal-like predators back to the late Messinian. In addition, it is possible that early jackals crossed to Spain from North Africa. [ABSTRACT FROM AUTHOR]

The article presents case report of a patient who developed hypertransaminasaemia while receiving docetaxel and cisplatin.

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COVID-19 became a global health emergency because it threatened the collapse of health systems as demand for health goods and services and their relative prices surged. Governments responded with lockdowns and transfers. Empirical evidence shows that lockdowns and healthcare saturation contribute to explain the cross-country variation in GDP drops even after controlling for COVID-19 cases and mortality. We explain this output-pandemia trade-off as resulting from a shock to subsistence health demand that increases with capital utilization and economic activity in a model with entrepreneurs and workers. The health system saturates as the gap between supply and subsistence narrows, which worsens consumption and income inequality. An externality distorts utilization, because firms do not internalize that lower utilization reduces healthcare saturation. Lockdowns and transfers to workers are the optimal policy response. Quantitatively, strict lockdowns and large transfers yield sizable welfare gains because they neutralize the utilization externality and prevent a sharp rise in inequality. Welfare and output costs vary in response to small parameter changes or deviations from optimal policies. Weak lockdowns coupled with weak transfers programs are the worst alternative and yet are in line with what several emerging and least developed countries implemented. JEL Classification E60 * H0 * I18, 1 Introduction A distinguishing feature of the COVID-19 pandemia is that, unlike other viral illnesses that are either more lethal (e.g., Ebola, MERS) or just as contagious but less severe [...]

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