Galen on Infertility in the Commentary on the Hippocratic Aphorisms, Book 5

The fifth book of the Hippocratic Aphorisms represents an important source for the history of ancient gynecology: exactly the half of this book (thirty-six of its seventy-two aphorisms) is concerned with gynecological problems. Some aphorisms (especially Aph. V 59, 62 and 63) deal with obstacles to pregnancy and sterility of women and/or men. The aim of this paper is to investigate how Galen understood and explained these aphorisms, whose interpretation covers a very long section of his Commentary on the Hippocratic Aphorisms. In these pages of Galen’s Commentary, we find very interesting observations both on the medical content and on philological problems raised from the Hippocratic text. On the one hand, Galen explains female infertility according to his own theory of mixture (κρᾶσις) and refers to the figure of the midwife, as Plato described her in the Theaetetus, for diagnosing it. On the other hand, he has to deal with the inconsistency of Aph. V 63 on male sterility, the authenticity of which is questioned on account of some incoherencies Galen detects in the alleged Hippocratic text

ANALISIS PENGARUH KUALITAS LAYANAN APLIKASI MOBILE BANKING DAN PRODUK BANK TERHADAP KEPUASAN NASABAH UNITED OVERSEAS BANK INDONESIA DI BATAM

Bank services in physical or non-physical service clould be another strategy to win the attention of customer. The satisfaction from the customers is very highly important to establish since the industry is very competitive. UOB Bank is one of the private banks in Batam city that provide mobile banking application which called TMRW and it has several bank products like housing credit, credit cards, deposit and other financial product as well. Research here is conducted to explore the effect of the mobile application of the UOB called TMRW along with the product tha effect satisfaction of the customer. The researcher took random sample in this case with the regresseion method for the hypthesis test. The result of the researh showed the profile of the responden averagely has minimum 2 bank product on their possesion and 100% using the TMRW application. The Regression showed that partially the qualitity of the mobile application TMRW has effects to the customers satisfaction, the variabel of the Quality of bank product has effects for the customers satifaction. Simultaneously quality of the mobile app TMRW and Quality of the bank product has effects for the customers satisfactio

Incontro e scontro di culture: i confinati antifascisti a Eboli e ad Aliano

The political confinement was one of the instrument of persecution of the Fascist regime. This paper aims to analyze how this form of limitation of freedom, based on expulsion and isolation, political but also cultural, economic and social, has helped to overcome the concept of border. The political confinement made new relationships between the Antifascists deported and the local population. The famous novel by Carlo Levi "Christ Stopped at Eboli" describes how the men and women sent to Aliano, the town where Carlo Levi was actually imprisoned, transformed punitive experience in an encounter between different cultures, thanks to the contact with the South of Italy. What happened to Eboli, the country of Salerno mentioned in the title? Are there differences between the case of Eboli, Aliano and the South of Italy?Through the analysis of the 250 letters sent by seventy Antifascist confinemented to Eboli and Aliano, we can identify some of the main policy results, economic, cultural and social produced by Fascist political confinement in Eboli and Aliano. The historical record, made by seventy political deported, helped the renewed Italian political class to face a problem known as the "Southern question".

PHARMACOGENETICS OF FLUOROPYRIMIDINES: FROM THE IMPLEMENTATION OF GUIDELINES TO IDENTIFICATION OF NOVEL GERMLINE VARIANTS RELATED TO TOXICITY

La medicina di precisione trova un valido alleato nella farmacogenomica che mira a identificare varianti genetiche coinvolte nella risposta terapeutica. Nei trattamenti su misura, \ue8 necessaria un'attenzione particolare per quei farmaci che mostrano un basso indice terapeutico, come le fluoropirimidine (FL) che rappresentano la spina dorsale nella gestione di molti tipi di tumori solidi. FL portano a una grave grave tossicit\ue0 (G 653) in una percentuale considerevole di pazienti, causando occasionalmente la morte dei pazienti. Le FL sono metabolizzate principalmente dalla diidropirimidina deidrogenasi (DPD; DPYD) in metaboliti inattivi. Attualmente sono note solo quattro varianti genetiche della DPYD (DPYD * 2A, DPYD * 13, DPYD c.2846A> T e DPYD-HapB3) che riducono l'attivit\ue0 della DPD e di conseguenza sono associate alla tossicit\ue0 correlata alla FL. I quattro SNP utilizzati nel test di genotipizzazione sono raccomandati prima dell\u2019inizio di un trattamento basato su FL. Nonostante l'elevata specificit\ue0, questo test ha dimostrato una bassa sensibilit\ue0, lasciando inspiegabile la maggior parte degli eventi tossici. Recentemente, \ue8 emerso il ruolo precedentemente trascurato di nuove e rare varianti genetiche nella variabilit\ue0 intra-individuale nella risposta ai farmaci. In questa tesi di dottorato, abbiamo mirato a migliorare le conoscenze sulla validit\ue0 clinica e l'utilit\ue0 clinica del test diagnostico clinico DPYD proposto dalle attuali linee guida farmacogenomiche, studiando l'impatto delle quattro varianti della DPYD sulla tossicit\ue0 correlata alle fluoropirimidine e ai costi per la gestione della tossicit\ue0 in grandi coorti di pazienti. Inoltre, abbiamo analizzato il contributo di varianti genetiche nuove e rare in una serie di farmaco-geni nello sviluppo della tossicit\ue0 correlata alle fluoropirimidine. Qui, mostriamo come il test dei quattro SNP per DPYD consente di identificare un gran numero di pazienti che svilupperanno gravi reazioni avverse al trattamento a base di FL in un gruppo di 763 pazienti oncologici. Ci\uf2 \ue8 particolarmente vero se i quattro SNP DPYD sono disposti nel noto punteggio di attivit\ue0 genica (GAS) che pesa ciascun SNP in base al suo impatto specifico sul fenotipo della proteina DPD. Abbiamo anche dimostrato, in un sottogruppo di 550 pazienti con carcinoma del colon-retto, come il genotipo DPYD per il set di quattro SNP o il GAS siano correlati al costo di gestione per gravi tossicit\ue0 correlate alla FL. Questa scoperta ha notevoli implicazioni nell'utilit\ue0 del test che ne garantisce l'applicazione nella pratica clinica di routine. Successivamente abbiamo analizzato, con un approccio di sequenziamento di nuova generazione, il ruolo potenziale di varianti nuove o rare nei geni nella via di disintossicazione in 108 pazienti che non presentano le ben note 4 varianti di rischio DPYD e sviluppato grave tossicit\ue0 correlata al FL. Abbiamo identificato 9 rare varianti di DPYD, 3 erano missense molto rare e 6 erano missense uniche. In confronto, una popolazione di 106 pazienti trattati con un regime basato su FL, senza alcuna reazione avversa, ha mostrato una riduzione di nuove varianti (valore p = 0,001, secondo il test esatto di Fisher). Inoltre, come previsto, abbiamo trovato un arricchimento statisticamente significativo di varianti esoniche rare, molto rare e nuove sulla DPYD nella coorte di pazienti con grave tossicit\ue0 rispetto a quelle senza. Nonostante la necessit\ue0 clinica di personalizzare il trattamento su ciascun paziente, ad oggi tradurre le informazioni genetiche di ciascun paziente in un'indicazione terapeutica rimane un compito impegnativo. Lo studio della farmacogenomica nel trattamento a base di FL ha gi\ue0 fornito marcatori utili e validi per la pratica clinica, lo studio di varianti genetiche rare e nuove potrebbe in futuro migliorare ulteriormente gli strumenti disponibili per una medicina di precisione nel trattamento del cancro.Precision medicine finds a valuable ally in pharmacogenomics which is aimed at identifying genetic variants involved in therapeutic response. In tailored treatments, a specific attention is required for those drugs showing a low therapeutic index, such as fluoropyrimidines (FL) which represent the backbone in the management of many types of solid tumours. FL lead to severe toxicity (G 653) in a considerable percentage of patients, occasionally resulting in patients death. FL are mainly metabolized by dihydropyrimidine dehydrogenase (DPD; DPYD) into inactive metabolite. At present only four DPYD genetic variants (DPYD *2A, DPYD *13, DPYD c.2846A>T and DPYD-HapB3) are known to decrease DPD activity and consequently to be associated to FL-related toxicity. The four SNP genotyping test is recommended before an FL-based treatment by international shared pharmacogenetic guidelines, Despite the high specificity, this test demonstrated a low sensitivity, leaving the majority of the toxic events unexplained. Recently, the previously neglected role of novel and rare genetic variants in the intra-individual variability in the response to drugs has emerged. In this PhD thesis, we aimed at improving the knowledge on the clinical validity and clinical utility of the DPYD clinical diagnostic test proposed by the current pharmacogenomic guidelines, by investigating the impact of the four DPYD variants on fluoropyrimidines-related toxicity and costs for toxicity management in large cohorts of patients. In addition, we analysed the contribution of novel and rare genetic variants in a set of pharmaco-genes in the development of fluoropyrimidines-related toxicity. Here, we show how the four-SNPs test for DPYD allow to identify a large number of patients who will develop severe adverse reactions to FL-based treatment in a group of 763 oncological patients. This is especially true if the four DPYD SNPs are arranged in the so-called gene activity score (GAS) weighing each SNP according to its specific impact on the DPD protein phenotype. We also demonstrated, in a subset of 550 colorectal cancer patients, how the DPYD genotype for the four-SNPs set or the GAS are related to the management cost for severe toxicities related to FL. This finding has notable implication in the utility of the test warranting its application in the routine clinical practice. We subsequently analyzed, by a next generation sequencing approach, the potential role of novel or rare variants in genes in the detoxification pathway in 108 patients that are wild type for the well-know 4 DPYD risk variants and developed severe FL-related toxicity. We identified 9 rare DPYD variants, 3 were very rare missense (c.G345C, p.M115I; c.A2060C p.D687A and c.A2137G, p.N713D), and 6 were singleton missense (c.A110G, p.D37G; c.G481A, p.E161K; c.C800T, p.T267I; c.G958A, p.G320R; c.A1110G, p.I370M;c.C1579T, p.P527S). in comparison, a population of 106 patients treated with a FL-based regimen, without any adverse reaction, displayed a depletion of novel variants (p value =0.001, by Fisher\u2019s Exact Test). Also, as expected, we found a statistically significant enrichment of rare, very rare and novel exonic DPYD variants in the cohort of patients with severe toxicity as compared to those without (P =0.0187, P =0.0187, P =0.0291, respectively, , by Fisher\u2019s Exact Test). Despite the clinical need of tailoring treatment on each patient, to date translating the genetic information of each patient into a therapeutic indication remains a challenging task. The study of the pharmacogenomics in FL-based treatment has already provided useful and valid markers for the clinical practice, the study of rare and novel genetic variants could in the future further improve available tools for a precision medicine in cancer treatment

INCREASING STUDENTS’ READING COMPREHENSION ACHIEVEMENT USING JIGSAW TECHNIQUE

Tujuan penelitian ini adalah untuk menemukan adakah peningkatan pencapaian pemahaman membaca siswa setelah diajari penggunaan teknik Jigsaw. Penelitian ini dilakukan karena nilai siswa masih rendah pada tes pemahaman membaca. Data diperoleh dari nilai Pretest-postest dan kuestioner. Data yang telah dikumpulkan dianalisis dengan menggunakan T-test melalui SPSS versi 17.0. Hasil analisis data menunjukkan bahwa nilai rata-rata posttest siswa di kelas eksperimen (68,47) lebih besar dari nilai rata-rata pretest siswa (57.41) dengan peningkatan nilai 11.06. Berdasarkan data analisis dapat disimpulkan bahwa ada peningkatan pencapaian dalam pemahaman membaca siswa setelah diajakan dengan menggunakan teknik Jigsaw.The aim of this research is to find out whether there is an increase of the students’ reading comprehension achievement after being taught using Jigsaw technique. This study was done based on the consideration that students still got low scores in reading comprehension test. The data were collected by employing Pretest-posttest items and questionnaire. The collected data were analyzed using Repeated Measure T-Test with Statistical Package for Social Science (SPSS) version 17.0. The result shows that the students’ mean score of posttest in experimental class (68.47) is higher than that in the pretest (57. 41) with the 11.06 gained score. It is concluded that there is an increase in students’ reading comprehension achievement after being taught using Jigsaw technique.Keywords: jigsaw technique, reading comprehension, students’ achievement

L’impatto dell’effetto imitativo sulle politiche di bilancio

This study investigates the association between peer effects and earnings smoothing amongst private Italian firms. Previous stud-ies provide compelling evidence that earnings smoothing is common practice amongst privately held European firms. A practice which is also spread amongst private Italian firms. Yet, the underlying assumption of this stream of empirical research is that firms engage in earnings smoothing practice independently of their peers’ choice, despite the extant theoretical literature has been long recognising the important role of mimicking competitors. We provide a bridge between these two streams of research by focus-ing on a sample of private Italian firms during the period 2014-2019. We adopt a two-stage-least square approach in which peer’s idiosyncratic EBITDA serves as instrumental variable for peers’ earnings smoothing. In line with our expectations built upon the rivalry theory, we document that the association between peers’ effects and earnings smoothing practices is statistically significant and economically meaningful. This result withstands a battery of alternative tests where we adopt different proxies for both earnings smoothing and the set of independent variables of our multivariate analysis. Our findings also confirm the pres-ence of a positive association between earnings smoothing and other factors that are traditionally documented in prior studies: lev-erage, sales growth, age, absence of prior year losses. Yet, peer effects appear to play a primary role amongst these factors. Overall, our study suggests that when private firms engage in earnings smoothing practices the distorting effects on the quality of financial reporting are not limited to their financial statements, but they worryingly spread over the financial statements of their competitors. Under these circumstances, mimicking peers is a severe obstacle against the representation of a true and fair view, which still represents the goal of financial reporting. This perspective has important implications for regulators and external con-trols that aim at increasing the level of enforcement of financial reporting rules. And identifying the distinctive features of the most imitated firms becomes fundamental in this respect. Future research can further explore this relation to identify the factors that can mitigate the influence of peers or assess the influence of peers on other reporting practices such as real earnings management

Depresión, ansiedad y estrés relacionado con miedo al COVID-19 en adolescentes de una institución educativa. Piura, 2022

El objetivo del presente estudio fue determinar la relación entre depresión, ansiedad, estrés y miedo al COVID 19 en adolescentes de una institución educativa Piura- 2022. El tipo de investigación fue de tipo aplicada diseño no experimental, descriptivo correlacional, constituida por una muestra total de 328 adolescentes, a los cuales se les aplicaron dos cuestionarios diseñados en función de los objetivos de investigación, para el análisis de datos constó de dos fases, en la primera se utilizó el análisis univariado la estadística descriptiva con frecuencias relativas y absolutas; según los niveles de las variables se clasificó en porcentajes de nivel alto, medio y bajo. Posteriormente se determinó la distribución normal de los datos a través de la prueba de Kolmogórov-Smirnov. Se encontró que el coeficiente de correlación de Spearman entre las variables depresión y miedo al COVID-19 fue igual .156* por lo tanto existe relación débil pero significativa (p<0.05); entre ansiedad y miedo al COVID-19 no existe correlación significativa (p>0.05); mientras que la relación entre estrés y miedo al COVID-19 la correlación fue débil pero significativa (p<0.05). De dichos resultados se concluyó que la depresión y el estrés están significativamente relacionados con el miedo a la enfermedad COVID-19 con un nivel de significancia p< 0.05, por otro lado, la ansiedad no está significativamente relacionada con el miedo al COVID-19

Análisis de la comercialización internacional del limón peruano en los periodos 2015-2019

El trabajo de investigación tuvo como propósito diagnosticar la situación del limón peruano en el mercado internacional y conocer los factores que influyen en este análisis. Teniendo como objetivo principal analizar la comercialización internacional del limón peruano en los periodos 2015-2019. El estudio correspondió a una investigación cualitativa. Esta investigación estuvo orientada a la investigación descriptiva por lo que se identificaron las características del mercado de limón peruano. El diseño de la investigación es no experimental, ya que se recopiló información con respecto al objeto de estudio, las cuales se han realizado sin la manipulación deliberada de variables. Este estudio fue de carácter global porque nuestra unidad de análisis se refirió a toda información disponible sobre comercialización internación del limón peruano en los periodos mencionados. La técnica empleada fue el análisis documental, donde se determinó la variación porcentual del limón peruano en el mercado internacional. Los resultados obtenidos determinaron que entre los periodos del 2015 al 2019 existió un crecimiento de la comercialización internacional del limón, teniendo como principal mercado de destino a Chile, se logró identificar las causas y se propuso más difusión de información sobre los programas que proporciona el Estado en beneficio de las Mypes y la diversificación productiva del limón peruano