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Gynecological Endocrinology articles from February 2004

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<a href="http://www.highbeam.com/Gynecological+Endocrinology/publications.aspx?date=200402" title="Articles and back issues from Gynecological Endocrinology">Gynecological Endocrinology articles</a>

Gynecological Endocrinology back issues from February 2004:

Results of in vitro fertilization cycles in women aged 43-45 years

Feb 01, 2004; ... Key words: IVF, ELDERLY WOMEN, OUTCOME, SUCCESS, PREGNANCY ABSTRACT Our objective was to evaluate the results of in vitro fertilization (IVF) cycles in the elderly (43-45 years old) female population. All consecutive women aged 43-45 years admitted to our IVF unit from January ...

Effect of contaminated preprocessed semen on fertilization rate and embryo quality in assisted reproductive techniques

Feb 01, 2004; ... Keywords: SEMEN, CULTURE, CONTAMINATION, FERTILIZATION, EMBRYO QUALITY, ART ABSTRACT We aimed to identify the sources and prevalence of semen contamination from masturbation and determine the effect of bacterospermia on fertilization rate and embryo quality in standard in vitro ...

Association of adenylate cyclase with an actin-like protein in the human myometrium

Feb 01, 2004; ... Key words: HUMAN MYOMETRIUM, ADENYLATE CYCLASE, cAMP, ACTIN, CYTOSKELETON, PURIFICATION ABSTRACT Regulation of muscle contraction by second messengers such as cAMP and regulation of the adenylate cyclase enzyme by the cytoskeleton have been previously described. However, the ...

Proliferation kinetics in adenomyosis during the menstrual cycle and during oral contraceptive use

Feb 01, 2004; ... Key words: P53 EXPRESSION, ADENOMYOSIS PROLIFERATION, KI-67, PROGESTINS ABSTRACT Our objective was to investigate the presence of focal p53 expression in relation to proliferation rates in adenomyotic lesions during the menstrual cycle and in women on oral contraception ....

Umbilical endometriosis in pregnancy: a case report

Feb 01, 2004; ... Key words: ENDOMETRIOSIS, PREGNANCY, UMBILICAL NODULE ABSTRACT To our knowledge, this is the first case reported in the literature of umbilical endometriosis in a pregnant woman. We report a case of umbilical endometriosis in a pregnant woman at 16 weeks of gestation. The patient ...

The osteoporosis dilemma

Feb 01, 2004; ... Few publications in the past few years have led to a change in the indication of an already established therapy; however, this is exactly what publication of the Women's Health Initiative (WHI) results achieved ibr hormone replacement therapy (HRT). All the recent reports regarding HRT have ...

Relationship between gonadotropin releasing hormone agonist dosage and in vitro fertilization outcome

Feb 01, 2004; ... Key words: GnRH-AGONIST, BODY MASS INDEX, IN VITRO FERTILIZATION ABSTRACT A prospective study in 132 women undergoing in vitro fertilization was performed in order to assess whether lower doses of gonadotropin releasing hormone agonists (GnRH-a) may ensure adequate oocyte ...

Adrenal response to adrenocorticotropic hormone stimulation in patients with premenstrual syndrome

Feb 01, 2004; ... Key words: STEROIDS, ALLOPREGNANOLONE, ACTH, PREMENSTRUAL SYNDROME, SERUM ABSTRACT Several studies have been performed during recent years to investigate the existence of a possible endocrine cause for premenstrual syndrome (PMS); the results reported are often discordant. Great ...

Thyroid hormone alteration in pre-eclamptic women

Feb 01, 2004; ... Key words: PRE-ECLAMPSIA, THYROID HORMONE, PREGNANCY ABSTRACT This study sought a possible relationship between preeclampsia and thyroid profile. In a case-control setting, total thyroxine (T^sub 4^), total tri-iodothyronine (T^sub 3^), free T^sub 4^, free T^sub 3^, thyroxine ...

The prognostic value of serum inhibin, 17[beta]-estradiol and progesterone in cases of hydatidiform mole

Feb 01, 2004; ... Keywords: HYDATIDIFORM MOLE, 17[beta]-ESTRADIOL, PROGESTERONE, INHIBIN ABSTRACT The purpose of this study was to provide a diagnostic and a prognostic variable that could easily be measured in the laboratory, and that would predict the need for future therapy of persistent ...

MULTIPLE PREGNANCIES: AN INEVITABLE CONSEQUENCE OF ART?

Feb 01, 2004; ... PL3 The incidence of multiple pregnancies has increased dramatically over the past twenty years due to widespread use of modern Assisted Reproduction Technologies (ART) and specially to the transfer of an excessive number of embryos in IVF cycles. To develop a scoring system to ...

HORMONE REPLACEMENT BEFORE AND AFTER BREAST CANCER

Feb 01, 2004; ... PL5 Postmenopausal Hormone Replacement Therapy (HT) has been reported to increase the risk for breast cancer (BC), especially when HT is current, combined and given long-term to lean women. The magnitude of the risk increase is smaller than seen with other known risk factors ...

NEW PROSPECTIVE IN THE MANAGEMENT OF FEMALE SEXUAL DYSFUNCTION: FROM PATHOPHYSIOLOGY TO THERAPIES

Feb 01, 2004; ... PL7 Our knowledge and understanding of the anatomy and physiology of the female sexual response and the pathophysiology of sexual female dysfunction is limited. Uased on our understanding of the physiology of the male erectile response, recent advances in modern technology, the study of ...

DYSFUNCTIONAL UTERINE BLEEDING DURING ADOLESCENCE

Feb 01, 2004; ... PL9 Dysfunctional Uterine Bleeding (DUB) defined as "abnormal uterine bleeding in the absence of organic cause", is the most frequent urgent gynecological problem during adolescence. DUB is a diagnosis of exclusion and thus systemic disease and local lesions must be ruled out ...

FOLLICULAR FLUID MARKERS OF OOCYTE DEVELOPMENTAL POTENTIAL

Feb 01, 2004; ... PS1 Follicular fluid (FF) is an environment in which the final phases of oocyte maturation take place. These events include metaphase and anaphase of the first meiotic division during which most of the ineiotic errors, responsible for age-related oocyte and embryo aneuploidy, are ...

GENOMICS OF ENDOMETRIAL RECEPTIVITY

Feb 01, 2004; ... PS3 The endonietrium is a specialized hormonally regulated tissue that is non-adhesive for embryos throughout most of the menstrual cycle in humans and other primates. Thus, endometrial receptivity is a self-limited period in which the endometrial epithelium (EE) acquires a functional ...

THE INFLAMMATORY RESPONSE DURING CONTROLLED OVARIAN HYPERSTIMULATION

Feb 01, 2004; ... PS5 Controlled ovarian hyperStimulation (COH) is apparently a key factor in the success of in vitro fcrtilization-embryo transfer. One of the major complications of COH is severe ovarian hyperstimulation syndrome (OHSS). OHSS was noted to be similar to vascular leak syndrome, which may ...

ESTROGEN, SYNAPTIC PLASTICITY AND HYPOTHALAMIC REPRODUCTIVE AGING

Feb 01, 2004; ... PS8 Neural control of reproduction by the periveiitricular area (PVA) of the brain is estrogen-sensitive. Remarkably, high levels of estrogen induce a paradoxical synaptic disengagement (PSD), e.g. during the prcovulatory period in females of all mammalian species that have been tested ....

HORMONAL CONTROL OF ANTIAPOPTOTIC GENES IN HUMAN NEURONS

Feb 01, 2004; ... PS10 Seladin-1/DHCR24 (Selective Alzheimcr's Disease Indicator) is a gene involved in human stcroidogenesis, which converts desmostcrol into cholesterol (Waterham et al., Am J Hum Genet, 69:685, 2001). This gene has been found to be mutated in a rare genetic disorder, named ...

PRETERM LABOUR: ROLE OF THE MYOMETRIUM

Feb 01, 2004; ... PS12 The onset of labour, both term and prcterm is preceded by a preparatory phase during which the uterus changes from a relatively inactive to a vigorously active organ in terms of contractility. Mechanisms involved in the regulation of uterine contractility significantly differ ...

PRETERM LABOUR AND DELIVERY - THERAPY: THE FUTURE

Feb 01, 2004; ... PS14 Preterm labour may be regarded as a syndrome with various aetiologies, e.g. abruptio of the placenta or infection of the mother. A common pathway through which the uterus is activated may involve receptor-mediated effects of oxytocin. This hormone is released from the posterior ...

RISEDRONATE AND OSTEOPOROSIS TREATMENT

Feb 01, 2004; ... PS16 Clinical trials with bisphosphonatcs opened a new era in the treatment of osteoporosis and - among them - risedronate played a significant role. Risedronate phase Hl clinical trials have been carried out either in post-menopausal or in corticosteroids induced osteoporosis ....

HORMONE REPLACEMENT THERAPY FOR THE PREVENTION OF OSTEOPOROSIS IN POSTMENOPAUSAL WOMEN

Feb 01, 2004; ... PS19 The use of HRT for ostcoporosis prevention is based on biology, epidemiology, animal and prcclinical data, observational studies and randomized clinical trials. This reduction is statistically significant, clinically relevant and, last but not the least, biologically plausible. The ...

ESTROGEN RECEPTOR POLYMORPHISMS AND WOMEN'S HEALTH AND DISEASE

Feb 01, 2004; ... PL1 The Human Genome project and the possibility to survey for many genes introduced the concept of "omic" research, coined by various researchers as proteomics, metabolomics, immunomics, toxicomics, structural genomics, functional gcnomics and also pharmacogenomics. Indeed, many ...

MOLECULAR GENETICS OF THE ANDROGEN RECEPTOR

Feb 01, 2004; ... PS21 Androgens are responsible for differentiation, development and maintenance of male phenotype and participate to growth and function of a variety of cell types and tissues. As the other steroid hormones, testosterone and dihydrotestosterone lead to a biological response through the ...

NEW MECHANISMS FOR STEROID HORMONE SIGNALING

Feb 01, 2004; ... PS23 In the last two decades, several studies have unveiled a series of original signaling mechanisms through which so-called "nuclear" receptors can mediate rapid actions of steroid hormones. These rapid signaling actions are independent by the synthesis of mRNA or protein, and are ...

ESTETROL, THE FORGOTTEN HUMAN FETAL ESTROGEN: AN ESTROGEN ANTAGONIST FOR THE BREAST

Feb 01, 2004; ... PL4 Introduction: Estetrol (E4) has been discovered almost 40 years ago (1905) by Diczfalusy. E4 is an estrogenic steroid, that differs from estriol (E3) only by an additional OH group in the alpha configuration on position 15 ( see figure 1) E4 has been studied as a potential marker for ...

NEUROENDOCRINE ASPECTS OF AMENORRHEA

Feb 01, 2004; ... PS26 Functional hypothalamic amcnorrhca (FHA) is characterized by reduced GnRH drive and mild hypcrcortisolemia.The behavioral antecedents leading to the development of nonorgamc forms of chronic anovulation and amenorrhea are variable. Dieting and excessive exercise are often initiated ...

AMENORRHEA: FROM DIAGNOSIS TO TREATMENT

Feb 01, 2004; ... PS28 The evaluation of secondary amenorrhea is conceptually organized around disruption of the menstrual cycle at three critical levels. These levels, the hypothalamus, the pituitary, and the ovary are the main targets for the complex feedback interactions that maintain the normal ...

SPRM: THERAPEUTIC POTENTIAL IN ENDOMETRIOSIS

Feb 01, 2004; ... PL6 Intracellular progesterone receptors (PR) play a central role in endometrial cyclicity. On one hand, PR-ligand complexes promote epithelial and stromal differentiation needed for the establishment and maintenance of pregnancy, and on the other, dissociation of these complexes at the ...

NEW MOLECULAR PATHWAYS IN ANGIOGENESIS

Feb 01, 2004; ... PS30 Angiogcncsis has developed into a major area of cancer research. Recently, several newly identified signalling pathways have been shown to play a role in both normal and pathological (including tumour) angiogenesis. Several of the molecules involved in these pathways have potential ...

PLACENTAL ANGIOGENESIS IN PHYSIOLOGY AND PATHOPHYSIOLOGY

Feb 01, 2004; ... PS33 Early human embryonic implantation initiates within a relatively avascular and hypoxic uterine environment. However, after the first 2-3 weeks of gestation the placenta develops two independent and intricate fetal and maternal circulations. Vascular branching allows chorionic villus ...

THE OESTROGENS; POLYVALENT AND PLURIPOTENT

Feb 01, 2004; ... PL8 The group of bio-regulatory steroid compounds known as the oestrogens are, we now understand, of great antiquity and, as a consequence, have been charged by evolutionary process with a broad range of activities. Their lipid-solubility, rapid interconversion and both receptor and ...

CONTROLLED OVARIAN HYPERSTIMULATION - THE IMPORTANT STEP IN ART. HOW TO CHOOSE THE BEST WAY OF STIMULATION?

Feb 01, 2004; ... PS35 The controlled ovarian hyperstiinulation (COH) is commonly applied as the first step in the assisted reproductive technics (ART).There are many methods to achieve this purpose.The study aim in our department was to compare the use of the four protocols of COH: clomiphene citrate ...

WHY PULSED ESTROGEN EXPOSURE RESULTS IN BETTER TARGET TISSUE SELECTIVITY: A HYPOTHESIS

Feb 01, 2004; ... PL10 Both oral and transdermal postnienopausal hormone replacement therapy (HT) aim to provide a steady mid-follicular serum concentration of estrogen. In contrast, (intranasal) pulsed es trogen therapy concentrates hormone exposure in the few hours following administration. The ...

GNRH AGONISTS VERSUS ANTAGONISTS

Feb 01, 2004; ... PS37 Modification of the amino acid structure of CInRH led to the availability of GnRH agonists and more recently (InRH antagonists for clinical use. Although both are effective in inhibiting premature release of LH during ovarian stimulation for assisted reproduction, the agonists have ...

POOR RESPONDERS: CAN WE IMPROVE THE OUTCOME?

Feb 01, 2004; ... PS39 Treating poor rcspondcrs remains a frustrating challenge. Varieties of strategies have been used to improve ovarian response.The first approach is to increase the dose of gonadotropins. However, raising the dose above 450 lU/d has little benefit. An alternative approach is the ...

ENDOMETRIOSIS: DIAGNOSIS

Feb 01, 2004; ... PS41 Endometriosis is a common gynaecological condition. However, making a diagnosis of endonictriosis may be delayed or missed, as [lie frequently associated symptoms, especially pain and infertility, may direct clinicians towards different paths of investigation. Screening ...

ROLE OF CUMULUS OOPHORUS IN IN VIVO OOCYTE FERTILIZATION

Feb 01, 2004; ... PS2 In the preovulatory follicle, granulosa cells lining the follicle wall promote selective degradation of perifollicular matrix, resulting in the formation of a rupture site at the ovarian surface. At the same time, the inner mass of granulosa cells surrounding the oocytc, namely ...

ROLE OF GNRH-ANALOGUES IN THE DIAGNOSIS AND TREATMENT OF ENDOMETRIOSIS

Feb 01, 2004; ... PS43 Endonietriosis affects 12% to 32% of women of reproductive age and may be either aymptomatic or severely symptomatic with pain, infertility or both. At laparoscopy, endometriotic implants will he visualized in 70% of women with pelvic pain and 80% of women with both pelvic pain and ...

VASCULAR ENDOTHELIAL GROWTH FACTOR IN EMBRYO ENDOMETRIAL INTERACTION

Feb 01, 2004; ... PS4 Implantation is a complex process that involves embryo apposition and attachment to the maternal endometrial epithelium, traversing adjacent cells of the endothelial lining, and invasion into the endometrial stroma. These processes involve a variety of molecules which play unique ...

HYPERPLASIA AND CARCINOMA OF THE ENDOMETRIUM

Feb 01, 2004; ... PS46 Four different genetic abnormalities may occur in endometrioid adenocarcinomas (microsatcllite instability and mutations in the PTEN, k-RAS and Beta-catenin genes), whereas nonendoinetrioid carcinomas often have p53 mutations and loss of hcterozygosity on several chromosomes ....

COLON CANCER

Feb 01, 2004; ... PS48 Carcinoma of the colon is common, the resulting mortality is high, an J the incidence of the disease varies according to the geographical location and dietary habits. Initial observations made from clinical case studies, formed the basis of a number of case-controlled and cohort ...

STEROID HORMONES AND RECEPTORS IN THE HUMAN BRAIN: INVOLVEMENT IN DEVELOPMENT, GENDER DISORDER, AGING AND DEMENTIA

Feb 01, 2004; ... PS7 Quite a number of structural and functional sex differences have been reported in the human hypothalamus and adjacent structures that may be related to not only reproduction, sexual orientation (hetero/homosexuality) and gender identity (male/female/transsexuahty),but also to the ...

POST-GENOMIC RESEARCH UNVEILS THE GENETIC BASIS OF INVASIVE METASTATIC PROGRAM

Feb 01, 2004; ... PS50 Invasive growth is a genetic program in which cell proliferation combines with cell-cell dissociation, movement, matrix degradation, and survival (apoptosis protection). It occurs under physiological conditions -during epithelial organ development, angiogencsis, wound healing- and ...

PROTEOMICS THE NEXT REVOLUTION IN MOLECULAR MEDICINE

Feb 01, 2004; ... PS52 The field of molecular medicine is moving beyond genomics to proteonncs. Clinical Proteomics is the application of proteomic technologies and informatic tools to clinical material.The translational nature of this technology provides unique challenges and unbounded opportunities that ...

PREMATURE OVARIAN FAILURE AS AN AUTOIMMUNE DISEASE

Feb 01, 2004; ... PS55 Since 1967 definition of Premature Ovarian Failure is "the unphysiological cessation of menses before the age of 40 y.o."The frequency in near 1%. Ovaries during different period of life from prepuberal, postpubcral o during reproductive stage can be the target of many ...

PROGESTIN REGULATION OF ESTROGEN SIGNALING IN BRAIN: CRUCIAL ISSUES FOR HORMONE REPLACEMENT THERAPY

Feb 01, 2004; ... PS9 Results of our studies indicate that progestins differ dramatically in their effects on neuronal responses and their interaction with estrogen. Specifically, in hippocampal neurons, 17[beta]7 -estradiol (E^sub 2^), progesterone and 19-norprogesterone, alone or in combination with E2, ...

PHYSIOPATHOLOGY AND TREATMENT OF AGE RELATED FEMALE REPRODUCTIVE FAILURE

Feb 01, 2004; ... PS57 The problem of infertility in advanced reproductive age is becoming of one major importance in society. Due to demographic changes related to longevity, people are more inclining towards conceiving at an older age, together with the tendency to delay child bearing until the career ...

THROMBIN INDUCES DECIDUAL PROTEASE AND CYTOKINE EXPRESSION IN THE PATHOGENESIS OF PRETERM MEMBRANE RUPTURE ASSOCIATED WITH ABRUPTION

Feb 01, 2004; ... PS11 Preterm delivery (PTD) is a leading cause of infant morbidity and mortality in the industrialized world. Approximately, 30% of PTDs follow preterm premature rupture of membranes (PPROM). There is abundant epidemiological and clinical evidence linking abruptio placenta or decidual ...

DIABETES MELLITUS

Feb 01, 2004; ... PS59 Epidemiological evidence for the relationship between deterioration of glucose tolerance and risk of cardiovascular disease (CVD) has been demonstrated in a vast number of investigations indicating that not only overt diabetes, but also insulin resistance are independent risk ...

ADRENAL DISORDERS

Feb 01, 2004; ... PS61 Glucocorticoid synthesis and release is tightly regulated by the pituitary and hypothalamus by negative feedback, and to a lesser extent by substances from the adrenal medulla, and neural inputs from the autonomie system. In addition to the glucocorticoid effects that cortisol has ...

THE "HONEST SIGNALLING THEORY" IN GYNECOLOGICAL ENDOCRINOLOGY: TEACHING AND RESEARCH IMPLICATIONS

Feb 01, 2004; ... PS63 Signalling theory has been developed in order to understand the relationship between individuals in the optic of evolutionary biology. We applied the theory in the field of gynaecological endocrinology using the hormonal regulation of the menstrual cycle as a model. A sample of 32 ...

PREDICTIVE FACTORS OF PRETERM LABOUR AND DELIVERY

Feb 01, 2004; ... PS13 Preterm labor is a syndrome that may be initiated by many causes, representing either a breakdown in the mechanisms responsible for maintaining uterine quiescence or an overwhelming of the normal parturition cascade. Several placental hormones and cytokines play a decisive role in ...

RECENT CLINICAL DATA AND THE ROLE OF HORMONE THERAPY TODAY

Feb 01, 2004; ... PS65 Continued scientific discussion regarding the results of the Women's Health Initiative Estrogen plus Progestogen Arm (WHl) is necessary to fully understand the implications of the data from this study. This presentation will focus on four specific topics related to WHl: 1) the ...

ROLE OF THROMBOPHILIAS IN PREGNANCY AND RECURRENT PREGNANCY LOSS

Feb 01, 2004; ... PS15 Hereditary thrombophilias may predispose to miscarriage, recurrent miscarriage (KM), intrauterinc growth retardation and prccclainpsia. Recent nictaanalyscs have associated FactorV Leiden (FVL) and Prothrombin gene mutation (G20201 A) with fetal loss and late obstetric ...

NEW SERMS, CAN THEY REPLACE HRT?

Feb 01, 2004; ... PS67 An ideal SERM would act as estrogen agonist in bone, vagina, brain and vascular wall but as estrogen antagonist in breast and endometrium. None of the SERMs on market so far (tamoxifen, toremifene, raloksifene) fulfill these criteria. Ospemifene is one of the newest SERMs, and its ...

PCOS: MOLECULAR CLUES TO PATHOPHYSIOLOGY

Feb 01, 2004; ... PS69 While the our studies have identified important correlations between increased steroidogenic enzyme gene expression and increased androgen biosynthesis in PClOS theca cells, they have not disclosed the upstream genes that are important for increased transcription. Furthermore, the ...

EVALUATION OF CLINICAL, BIOCHEMICAL AND ULTRASOUND PARAMETERS FOR THE POLYCYSTIC OVARIAN SYNDROME'S DIAGNOSIS

Feb 01, 2004; ... PS71 Polycystk: Ovarian Syndrome (PCOS) is the most common endocrine disorders among women in reproductive age, but diagnostic criteria used in clinical practice are still controversial. In the Rotterdam PCOS workshop of May 2003, however, has been written a consensus document, trying to ...

ALENDRONATE IN THE TREATMENT OF OSTEOPOROSIS IN POSTMENOPAUSAL WOMEN

Feb 01, 2004; ... PS18 During the very last years there have been several reports concerning the side effects of hormone replacement therapy (HRT). Many women are discarding HRT since those reports. Alternative therapies for osteoporosis treatment include the bysphosphonates and the SERMs.The ...

POLYCYSTIC OVARY SYNDROME (PCOS) AND INSULIN RESISTANCE: IMPLICATION FOR TREATMENT OF INFERTILITY

Feb 01, 2004; ... PS73 PCOS affects 6-10% of women of childbearing age, and is the most common cause of infertility due to anovulation. Women with P(X)S also have a risk of early (first trimester) pregnancy loss (EPL) that is 3- to 5-fold greater than that of normal women. It is now recognized ...

ESTROGEN RECEPTOR ACTIVITY IN REPRODUCTIVE AND NON REPRODUCTIVE ORGANS

Feb 01, 2004; ... PS20 We have recently generated a transgenic reporter mouse, named ERE-LUC- to study the state oftranscnptional activity of estrogen receptors (ER) in pathophysiological states. The mouse was generated using as a transgene a luciferasc reporter driven by a TK minimal promoter and a ...

THE NEED FOR TISSUE SELECTIVE MENOPAUSAL AGENTS

Feb 01, 2004; ... PS75 Menopause presents the clinician and the patient with two main problems - how to manage mcnopausal symptoms such as hot Rushes and second the prevention or treatment of osteoporosis. For decades hormonal replacement therapy (HRT), mostly combined oestrogen-progestin treatment, has ...

IS MAMMOGRAPHIC DENSITY, AS CURRENTLY MEASURED, A ROBUST SURROGATE MARKER FOR BREAST CANCER? - THE RADIOLOGICAL VIEW

Feb 01, 2004; ... PS77 Breast density refers to the prevalence of fibroglandular tissue in the breast. Density can be inferred from the mammogram because fibroglandular tissue attenuates x rays more heavily than does fat causing the signal on the mammogram to be low. Several investigators have ...

EFFECTS OF HORMONE THERAPY ON COGNITION AND BRAIN FUNCTION: IS THERE A CRITICAL PERIOD

Feb 01, 2004; ... S2 Prospective observational studies suggest that hormone therapy (HT) might confer protection agailist the development of Alzheimer's disease (Al)). In contrast, recent findings from the Women's Health Initiative Memory Study (WHIMS) indicated a doubling of the risk of all-cause ...