Ideological change in Israel : a study of legislations, civil servants and university students

Thesis (Ph.D.)--Michigan State University. Department of Political Science, 1965Includes bibliographical references (pages 251-253

Current aspects in the development of in-vitro spermatogenesis from pluripotent stem cells

Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu”, Chişinău, Republica MoldovaIntroducere. Infertilitatea masculină este o gravă problemă socială, incidența căreia continuă să crească, ce a determinat cercetătorii să caute modalități de a genera spermatozoizi funcționali prin metoda in vitro. Acest proces urmărește replicarea etapelor naturale ale spermatogenezei în condiții de laborator. Scopul lucrării. Evaluarea actualităților în dezvoltarea spermatogenezei in-vitro (SiV) din celule stem pluripotente, prin analiza metodelor noi de inginerie tisulară. Material și metode. Studiul a fost realizat prin analiza literaturii de profil din perioada 2021-2024. Au fost studiate bazele de date PubMed, Cochrane Library, Elsevier, Research Gate, NCBI, din care au fost selectate articolele ce elucidează tehnicile noi ale ingineriei tisulare și medicinei regenerative, precum culturile tisulare ex-vivo, bioreactoarele, sistemele microfluidice și schelele. Rezultate. Până acum, cultura tisulară ex-vivo a realizat SiV completă la ovine, prin utilizarea țesutului congelat din testicul de capră cu metoda de cultură a picăturii suspendate, însă metoda dată nu asigură SiV continuă, așadar au fost implementate metode noi pentru îmbunătățirea diferențierii. Utilizarea bioreactoarelor, oferă un mediu controlat ce susține creșterea și diferențierea celulară. Sistemele microfluidice permit replicarea condițiilor in-vivo prin echilibrarea hormonilor, factorilor de creștere, temperaturii și pH-ului. Schelele oferă un cadru structural care sprijină atașarea și creșterea celulară, imitând matricea extracelulară naturală. Așadar, la momentul actual toate etapele spermatogenezei pot fi replicate in-vitro. Concluzii. SiV reprezintă o tehnică de ultimă oră în medicina reproductivă, având potențialul de a depăși provocările legate de infertilitate și de a remodela noțiunile tradiționale de familie. Progresul în SiV deschide noi posibilități pentru tratamentul infertilității masculine.Background. Male infertility is a serious social problem, with its incidence continuously increasing, prompting researchers to seek methods to generate functional sperm through in vitro techniques. This process aims to replicate the natural stages of spermatogenesis in laboratory conditions. Objective of the study. To evaluate the current advancements in the development of in-vitro spermatogenesis (SiV) from pluripotent stem cells by analyzing new tissue engineering methods. Material and methods. The study was conducted by analyzing relevant literature from 2021- 2024. Databases such as PubMed, Cochrane Library, Elsevier, Research Gate, and NCBI were reviewed, and articles elucidating new techniques in tissue engineering and regenerative medicine were selected, including ex-vivo tissue cultures, bioreactors, microfluidic systems, and scaffolds. Results. So far, ex-vivo tissue culture has achieved complete SiV in ovines by using frozen goat testicular tissue with the hanging drop culture method. However, this method does not ensure continuous SiV, leading to the implementation of new methods to improve differentiation. The use of bioreactors provides a controlled environment that supports cell growth and differentiation. Microfluidic systems allow the replication of in vivo conditions by balancing hormones, growth factors, temperature, and pH. Scaffolds provide a structural framework that supports cell attachment and growth, mimicking the natural extracellular matrix. Therefore, currently, all stages of spermatogenesis can be replicated in vitro. Conclusion. SiV represents a cutting-edge technique in reproductive medicine, with the potential to overcome infertility challenges and reshape traditional notions of family. Advances in SiV open new possibilities for the treatment of male infertility

Comparative analysis of recommendations for the diagnosis and treatment of defects of descending of the testicles

Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu”, Chişinău, Republica MoldovaIntroducere. Criptorhidia sau testiculul necoborât, este cea mai frecventă anomalie genito-urinară la nou-născuții de sex masculin. În cele mai multe cazuri, testiculele vor coborî spontan până la vârsta de 3 luni, însă, dacă nu coboară până la 6 luni, probabilitatea coborârii spontane ulterior este scăzută. Aproximativ 1%-2% dintre băieții mai mari de 6 luni vor prezenta criptorhidie. Scopul lucrării. Efectuarea analizei comparative a recomandărilor de diagnostic și trat ament regăsite în ghidurile internaționale pentru defectele de coborâre a testiculelor. Material și metode. Au fost preluate si analizate ghidurile următoarelor structuri științifice internaționale: Asociația Americană de Urologie; Asociația Britanică a Chirurgilor Pediatri/Asociația Britanică a Chiru rgilor Urologici; Asociația Canadiană de Urologie; Asociația Europeană de Urologie. Rezultate. Ghidurile internaționale nu recomandă ultrasonografia ca metodă unică în stabilirea diagnosticului și indicațiilor de tratament chirurgical. Tratamentul hormonal cu HCG a criptorhidiei are un grad inferior de recomandare având în vedere rezultatele studiilor de referință. Orhiopexia se recomandă a fi efectuată între 6 și 18 luni, pentru a proteja potențialul fertil și a minimaliza riscul de modificări maligne. Pacienții cu criptorhidie unilaterală au o rată a infertilității de până la 10%. Această rată este mai mare la pacienții cu criptorhidie bilaterală, cu test icule necoborâte intraabdominale sau care au suferit orhio pexie întârziată. Pacienții cu un testicul necoborât au un risc de 3 ori mai mare de cancer testicular, comparativ cu populația generală. Concluzii. Referirea pacientului în termeni restrânși la un specialist în urologie pediatrică cu corecția chirurgicală în timp util, pot îmbunătăți potențialul fertil și pot scădea ratele de malignizare a testiculelor criptorhidice sau ex-criptorhidice.Introduction. The most frequent genitourinary defect in male neonates is cryptorchidism, which refers to an undescended testicle. By the age of three months, the testicles will usually descend on their own. If the testicles do not descend by 6 months of age, the chances of spontaneous descent thereafter are limited. Cryptorchidism affects approximately 1-2% of boys over the age of 6 months. Objec tive of the study. Carrying out the comparative analysis of the diagnostic and treatment recommendations found in the international guidelines for undescended testis. Material and methods. The guidelines of the following international scientific societies were taken over and analyzed: American Urology Association; British Association of Pedi atric Surgeons/British Association of Urological Surgeons; Canadian Urological Association; European Association of Urology. Results. International guidelines do not recom mend ultrasonography as the only method of diagnosis before surgical treatment. Hormonal treatment with HCG in cryptorchidism has a lower degree of recommendation. Or chiopexy is recommended to be performed between 6 and 18 months, to protect the fertile potential and minimize the risk of malignancy. Patients with unilateral cryptorchidism have an infertility rate of up to 10%. This rate is even higher in patients with bilateral cryptorchidism, intra-abdominal undescended testes, or who have undergone delayed orchiopexy. Patients with an undescended testicle have a 3-fold increased risk of testicular cancer compared to the general population. Conclusions. Narrowly referring the patient to a pediatric urologist with timely surgical correction can increase the fertile potential and decrease the rates of malignancy of cryptorchid or ex-cryptorchid testes

The role of hyperprolactinemia in testosterone deficiency in men

Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu”, Chişinău, Republica MoldovaIntroducere. Prevalența hiperprolactinemiei la bărbați cu niveluri scăzute de testosteron (T) nu a fost bine stabilită. Mai multe condiții și factori au fost asociate cu hiperprolactinemia, inclusiv tumori, condiții comorbide și medicamente. Deși tumorile hipofizare sunt relativ rare la bărbații cu T scăzut, printre cei care sunt găsiți cu hiperprolactinemie, ele reprezintă principala cauză etiologică fiind identificată la 41% din cazuri. Scopul lucrării. Evaluarea rolului hiperprolactinemiei în deficitul de testosteron la bărbații cu accent pe valorile serice de importanță practică a prolactinei. Material și metode. Studiul a fost realizat prin analiza literaturii de profil din perioada 2010-2024. Au fost studiate bazele de date PubMed, Cochrane Library, Elsevier, Research Gate, NCBI, din care au fost selectate cele mai relevante articole conform scopului stabilit. Rezultate. Mecanismul specific prin care hiperprolactinemia cauzează scăderea T nu a fost elucidat definitiv, deși include mecanisme directe și indirecte. Prezența unui adenom hipofizar (secretor sau non-secretor) poate duce la suprimarea GnRH/LH sau la distrugerea celulelor producătoare de GnRH/LH cu scăderi ulterioare în producția de T. De asemenea, PRL poate acționa direct asupra hipofizei, în inhibarea secreții de LH și T. De menționat, din punct de vedere diagnostic, hiperprolactinemie apare în absența macroprolactinemiei, care altfel ar putea duce la niveluri ridicate de prolactină fără simptome asociate. Diferențierea între aceste două condiții și testarea diagnostică sunt recomandate ca măsuri de rutină în abordarea bărbaților cu hiperprolactinemie. Concluzii. Din punct de vedere practic, nivelurile de PRL <50 ng/mL sunt rareori asociate cu patologie semnificativă, în timp ce nivelurile mai mari (>250 ng/ml) sunt corelate pozitiv cu probabilitatea crescândă de patologie intracraniană, iar nivelurile >500 ng/ml sunt diagnostice pentru macroprolactinom.Background. The prevalence of hyperprolactinemia in men with low testosterone (T) levels has not been well established. Various conditions and factors have been associated with hyperprolactinemia, including tumors, comorbid conditions, and medications. Although pituitary tumors are relatively rare in men with low T, among those found to have hyperprolactinemia, they represent the main etiological cause, being identified in 41% of cases. Objective of the study. To evaluate the role of hyperprolactinemia in testosterone deficiency in men, with a focus on the practical significance of serum prolactin levels. Material and methods. The study was conducted through an analysis of relevant literature from the period 2010-2024. Databases such as PubMed, Cochrane Library, Elsevier, Research Gate, and NCBI were reviewed, and the most pertinent articles were selected according to the established objective. Results. The specific mechanism by which hyperprolactinemia causes a decrease in T has not been definitively elucidated, although it involves both direct and indirect mechanisms. The presence of a pituitary adenoma (secretory or non-secretory) can lead to the suppression of GnRH/LH or the destruction of GnRH/LH-producing cells, resulting in subsequent decreases in T production. Additionally, PRL can act directly on the pituitary gland, inhibiting the secretion of LH and T. Notably, from a diagnostic perspective, hyperprolactinemia occurs in the absence of macroprolactinemia, which could otherwise lead to elevated prolactin levels without associated symptoms. Differentiating between these two conditions and diagnostic testing are recommended as routine measures in the approach to men with hyperprolactinemia. Conclusion. From a practical standpoint, PRL levels <50 ng/mL are rarely associated with significant pathology, while higher levels (>250 ng/mL) are positively correlated with an increased likelihood of intracranial pathology, and levels >500 ng/mL are diagnostic for macroprolactinoma

Актуальные проблемы диагностики и лечения дефицита тестостерона у мужчин репродуктивного возраста

Rezumat Actualmente, un număr tot mai mare de bărbați tineri și de vârstă mijlocie sunt în căutarea tratamentului pentru simptomele legate de nivelul scăzut de testosteron, care includ depresia, oboseala cronică, libidoul scăzut, disfuncția erectilă și/sau infertilitatea. În situațiile în care conceperea unui copil nu este un obiectiv pe termen scurt sau mediu, prezervarea funcției reproductive necesită a fi considerată în contextul tratamentului oferit. Având în vedere caracterul adeseori idiopatic al deficitului de testosteron, în special pentru bărbații de vârstă reproductivă, alegerea metodei de tratament devine și mai dificilă, în contextul în care evidența științifică și gradul de recomandare a diverselor tratamente sunt slabe. A fost efectuată analiza literaturii contemporane, cu utilizarea principalelor baze de date, inclusiv PubMed, Hinari, SpringerLink și Scopus (Elsevier). S-a constatat că o treime dintre bărbații infertili cu vârsta sub 50 de ani sunt hipogonadali. Corelarea rezultatului spermogramei cu nivelul de testosteron a identificat un deficit la 16,7% dintre bărbații cu azoospermie obstructivă, 45% dintre bărbații cu azoospermie non-obstructivă, 42,9% dintre bărbații cu oligozoospermie și/sau astenozoospermie și 35,3% dintre bărbații cu parametri normali ai spermei. Terapia de substituție cu testosteron, deși eficientă în abordarea majorității simptomelor hipogonadismului, are efecte negative asupra funcției testiculare. Consilierea ar trebui să includă o discuție amănunțită a riscurilor și beneficiilor, cu accent pe supresia spermatogenezei pentru bărbații de vârstă reproductivă care doresc să-și mențină potențialul de reproducere.Summary Currently, an increasing number of young and middle-aged men are seeking treatment for symptoms related to low testosterone levels, which include depression, chronic fatigue, low libido, erectile dysfunction and/or infertility. In situations where conceiving a child is not a short- or medium-term goal, the preservation of reproductive function needs to be considered in the context of the treatment offered. Testosterone deficiency is often of unknown origin especially in men of reproductive age, and the choice of treatment method becomes even more difficult, in the context where the scientific evidence and degree of recommendation of various treatments is weak. Literature review was performed using major databases including PubMed, Hinari, SpringerLink and Scopus (Elsevier). One third of infertile men under the age of 50 were found to be hypogonadal. Correlation of spermogram result with testosterone level identified deficiency in 16.7% of men with obstructive azoospermia, 45% of men with non-obstructive azoospermia, 42.9% of men with oligozoospermia and/or asthenozoospermia and 35.3% of men with normal sperm parameters. Testosterone replacement therapy, although effective in addressing most symptoms of hypogonadism, has negative effects on testicular function. Counseling should include a thorough discussion of risks and benefits with an emphasis on spermatogenesis suppression for men of reproductive age who wish to maintain their reproductive potential.Резюме В настоящее время все большее число мужчин молодого и среднего возраста обращаются за лечением по поводу симптомов, связанных с низким уровнем тестостерона, которые включают депрессию, хроническую усталость, низкое либидо, эректильную дисфункцию и/или бесплодие. В ситуациях, когда зачатие ребенка не является краткосрочной или среднесрочной целью, сохранение репродуктивной функции необходимо рассматривать в контексте предлагаемого лечения. Дефицит тестостерона часто имеет неизвестное происхождение, особенно у мужчин репродуктивного возраста, и выбор метода лечения становится еще более трудным в контексте, когда научные данные и степень рекомендаций различных методов лечения слабы. Обзор литературы проводился с использованием основных баз данных, включая PubMed, Hinari, SpringerLink и Scopus (Elsevier). У трети бесплодных мужчин в возрасте до 50 лет выявлен гипогонадизм. Корреляция результата спермограммы с уровнем тестостерона выявила его дефицит у 16,7% мужчин с обструктивной азооспермией, у 45% мужчин с необструктивной азооспермией, у 42,9% мужчин с олигозооспермией и/или астенозооспермией и у 35,3% мужчин с нормальными показателями спермы. Заместительная терапия тестостероном, хотя и эффективна в устранении большинства симптомов гипогонадизма, оказывает негативное влияние на функцию яичек. Консультирование должно включать тщательное обсуждение рисков и преимуществ с акцентом на подавление сперматогенеза для мужчин репродуктивного возраста, желающих сохранить свой репродуктивный потенциал

Male infertility microsurgical techniques treatments

Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu”, Chişinău, Republica MoldovaIntroducere. Infertilitatea a fost prezentată ca un obstacol complex pentru sănătatea reproductivă, afectând aproximativ 15% dintre cuplurile din Statele Unite și peste 180 de milioane de cupluri la nivel mondial. Bărbații au fost considerați responsabili exclusiv în 20% din cazuri, contribuind suplimentar cu 30-40%. Avansările recente și abundența tehnicilor de microchirurgie au oferit speranță pentru o reducere semnificativă a acestor statistici. Scopul lucrării. A fost efectuată o revizuire cuprinzătoare a tehnicilor microchirurgicale în infertilitatea masculină și a impactului acestora asupra sănătății reproductive. Material și metode. Informațiile au fost obținute din PubMed, NIH și Atlasul de Microchirurgie a Infertilității Masculine al lui Marc Goldstein. Rezultate. Tehnicile microchirurgicale care au adresat infertilitatea masculină au fost precise și adesea au abordat direct patofiziologia bolii, făcându-le eficiente și foarte specializate în procedurile lor. Vasovasostomia și Vasoepididimostomia microchirurgicală au restabilit fluxul spermatic prin re-anastomozarea canalului deferent, direct sau la epididim. Aspirația Spermatică Epididimală Microchirurgicală și Recoltarea Spermei Testiculare au utilizat intervenția microchirurgicală pentru recoltarea spermei din epididim sau țesutul testicular, ocolind orice obstrucții în eliberarea spermei. În cazurile de azoospermie obstructivă, aceste proceduri au fost remarcabil de eficiente. Rezecția Transuretrală a Ductelor Ejaculatoare (TURED) a abordat obstrucția ductelor ejaculatoare prin rezecția endoscopică a țesutului obstructiv, restabilind fluxul normal al spermei. Aceste intervenții microchirurgicale au avut impacturi majore asupra factorului de infertilitate masculină. Asociate cu tehnologiile de reproducere asistată, cum ar fi fertilizarea in vitro (FIV), infertilitatea la cupluri ar putea deveni în curând o problemă a trecutului. Concluzii. Infertilitatea masculină, cunoscută pentru natura sa polietiologică și complexitățile anatomiei și fiziologiei reproductive masculine, a reprezentat o provocare semnificativă în medicina reproductivă. Tehnicile avansate de microchirurgie au oferit soluții promițătoare, posibil permițând concepția pentru cuplurile considerate anterior incapabile să conceapă.Background. Infertility presents a complex obstacle to reproductive health, affecting 15% of couples of reproductive ages and over 180 million couples worldwide. Males are solely responsible in 20% of cases and contribute to an additional 40-50%. Recent advancements in microsurgery offer hope for a significant reduction in these statistics. Objective of the study. Comprehensive review of microsurgical techniques in male infertility and their impact on reproductive health. Material and methods: Information was obtained from PubMed, NIH, and the Atlas of Male Infertility Microsurgery Marc Goldstein. Results. Microsurgical techniques addressing male infertility are precise and often directly target the pathophysiology of the disease, making them highly effective. Microsurgical Vasovasostomy and Vasoepididymostomy restore spermatic flow by re-anastomosing the deferens canal, either directly or to the epididymis. Microsurgical Epididymal Sperm Aspiration and Testicular Sperm Retrieval allow for sperm retrieval from the epididymis or testicular tissue, bypassing obstructions. In obstructive azoospermia, these procedures are notably effective. Transurethral Resection of the Ejaculatory Ducts (TURED) addresses ejaculatory duct obstruction via endoscopic resection, reinstating normal semen flow. Paired with assisted reproductive technologies like IVF, these interventions significantly impact male infertility, potentially solving infertility for many couples. Conclusion. Male infertility, known for its polyetiological nature and the complexities of male reproductive anatomy and physiology, poses a significant challenge in reproductive medicine. Advanced microsurgical techniques offer promising solutions, potentially enabling conception for couples previously deemed unable to conceive

Role of genetic polymorphism of follicle stimulating hormone receptor in couple infertility

Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu”, Chişinău, Republica MoldovaIntroducere. Infertilitatea afectează multe cupluri la nivel global, iar polimorfismul genetic al receptorului hormonului foliculostimulant (FSHR) reprezintă un factor important. Această lucrare revizuiește literatura pentru a evalua impactul acestor variații genetice asupra fertilității. Scopul lucrării. Scopul lucrării este de a evalua și sintetiza dovezile privind rolul polimorfismului genetic al receptorului FSHR în infertilitatea cuplurilor. Material și metode. Studiul este un review sistematic al literaturii, incluzând articole din PubMed, Scopus și Web of Science, publicate între 2000 și 2023. Criteriile de selecție au vizat studii care investighează legătura dintre polimorfismul FSHR și infertilitate. Analize statistice descriptive au fost utilizate pentru a sintetiza rezultatele. Rezultate. Analiza literaturii arată că variantele Ser680Asn și Ala307Thr ale receptorului FSHR sunt asociate cu o reducere a funcției ovariene și a ratei de succes a concepției. Aproximativ 35% dintre femeile cu varianta Ser 680Asn prezintă niveluri ridicate de FSH și răspuns ovarian scăzut (p < 0,05). Circa 25% dintre femeile cu mutația Ala307Thr necesită doze mai mari de FSH pentru stimulare ovariană eficientă (p <0,01). Concluzii. Polimorfismul genetic al receptorului FSHR, în special variantele Ser680Asn și Ala307Thr, influențează semnificativ infertilitatea, afectând funcția ovariană și succesul concepției. Aceste descoperiri subliniază importanța testelor genetice în evaluarea infertilității.Background. Infertility affects many couples globally, and the genetic polymorphism of the follicle stimulating hormone receptor (FSHR) is an important factor. This paper reviews the literature to assess the impact of these genetic variations on fertility. Objective of the study. The aim of the paper is to evaluate and synthesize evidence on the role of FSHR receptor genetic polymorphism in couples’ infertility . Material and methods. The study is a systematic review of the literature, including articles from PubMed, Scopus and the web of Science, published between 2000 and 2023. The selection criteria concerned studies investigating the link between FSHR polymorphism and infertility. Descriptive statistical analyses were used to synthesize the results. Re sults . Literature analysis shows that the SER680ASN and Al a307Thr variants of the FSHR receptor are associated with a reduction in ovarian function and conception success rate. Approximately 35% of women with the Ser680Asn variant have high levels of FSH and low ovarian response (p < 0.05). About 25% of women with the ala307thr mutation require higher doses of FSH for effective ovarian stimulation (p < 0.01). Conclusions. FSHR receptor genetic polymorphism, especially ser680asn and Ala307Thr variants, significantly influence infertility, affecting ovarian function and conception success. These findings underscore the importance of genetic testing in assessing infertility

Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer

SignificanceImmunotherapy options for immune cold tumors, like prostate cancer, are limited. We show that AR downregulates MHCI expression/antigen presentation and that AR inhibition improves T-cell responses and tumor control. This suggests that treatments combining AR inhibitors and checkpoint blockade may improve tumor immune surveillance and antitumor immunity in patients

Alcohol use and burden for 195 countries and territories, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016

Background Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older. Methods Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health. Findings Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2.2% (95% uncertainty interval [UI] 1.5-3.0) of age-standardised female deaths and 6.8% (5.8-8.0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3.8% (95% UI 3.2-4-3) of female deaths and 12.2% (10.8-13-6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2.3% (95% UI 2.0-2.6) and male attributable DALYs were 8.9% (7.8-9.9). The three leading causes of attributable deaths in this age group were tuberculosis (1.4% [95% UI 1. 0-1. 7] of total deaths), road injuries (1.2% [0.7-1.9]), and self-harm (1.1% [0.6-1.5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27.1% (95% UI 21.2-33.3) of total alcohol-attributable female deaths and 18.9% (15.3-22.6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0.0-0.8) standard drinks per week. Interpretation Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.Peer reviewe

Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49\ub74% (95% uncertainty interval [UI] 46\ub74–52\ub70). The TFR decreased from 4\ub77 livebirths (4\ub75–4\ub79) to 2\ub74 livebirths (2\ub72–2\ub75), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83\ub78 million people per year since 1985. The global population increased by 197\ub72% (193\ub73–200\ub78) since 1950, from 2\ub76 billion (2\ub75–2\ub76) to 7\ub76 billion (7\ub74–7\ub79) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2\ub70%; this rate then remained nearly constant until 1970 and then decreased to 1\ub71% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2\ub75% in 1963 to 0\ub77% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2\ub77%. The global average age increased from 26\ub76 years in 1950 to 32\ub71 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59\ub79% to 65\ub73%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1\ub70 livebirths (95% UI 0\ub79–1\ub72) in Cyprus to a high of 7\ub71 livebirths (6\ub78–7\ub74) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0\ub708 livebirths (0\ub707–0\ub709) in South Korea to 2\ub74 livebirths (2\ub72–2\ub76) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0\ub73 livebirths (0\ub73–0\ub74) in Puerto Rico to a high of 3\ub71 livebirths (3\ub70–3\ub72) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2\ub70% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill &amp; Melinda Gates Foundation