Medical Specialties Commons^™

Knowledge And Awareness Regarding Cervical Cancer And Uptake Of Pap Smear Among Women In Karachi, Pakistan, Shama Razzaq, Sayeeda Amber Sayed Amber Sayeeda Amber Sayed, Sumera Aziz Ali

Community Health Sciences

Objective: To determine the knowledge regarding cervical cancer, its symptoms and risk factors among women of 18 years and above attending the gynecology OPD in two public hospitals Karachi, Pakistan.
Methodology: A cross-sectional survey was held from February to June 2013 in Karachi, Pakistan. 384 females aged 18 years and above attending gynecology clinics in two public sector hospitals were taken through non-probability sampling method. The knowledge was assessed using a point scale method which had binary response i.e. correct and incorrect. A score of 50% (≥ 11 correct responses) was considered as optimum knowledge.
Results: Overall knowledge of cervical …

Cervical Ectropion May Be A Cause Of Desquamative Inflammatory Vaginitis., Leia Mitchell, Michelle King, Heather Brillhart, Andrew Goldstein

Obstetrics and Gynecology Faculty Publications

Desquamative inflammatory vaginitis is a poorly understood chronic vaginitis with an unknown etiology. Symptoms of desquamative inflammatory vaginitis include copious yellowish discharge, vulvovaginal discomfort, and dyspareunia. Cervical ectropion, the presence of glandular columnar cells on the ectocervix, has not been reported as a cause of desquamative inflammatory vaginitis. Although cervical ectropion can be a normal clinical finding, it has been reported to cause leukorrhea, metrorrhagia, dyspareunia, and vulvovaginal irritation. Patients with cervical ectropion and desquamative inflammatory vaginitis are frequently misdiagnosed with candidiasis or bacterial vaginosis and repeatedly treated without resolution of symptoms. We report the case of a 34-year-old woman …

Ultrasound Monitoring Of Extant Adnexal Masses In The Era Of Type 1 And Type 2 Ovarian Cancers: Lessons Learned From Ovarian Cancer Screening Trials, Eleanor L. Ormsby, Edward J. Pavlik, John P. Mcgahan

Obstetrics and Gynecology Faculty Publications

Women that are positive for an ovarian abnormality in a clinical setting can have either a malignancy or a benign tumor with probability favoring the benign alternative. Accelerating the abnormality to surgery will result in a high number of unnecessary procedures that will place cost burdens on the individual and the health delivery system. Surveillance using serial ultrasonography is a reasonable alternative that can be used to discover if changes in the ovarian abnormality will occur that favor either a malignant or benign interpretation. Several ovarian cancer screening trials have had extensive experiences with changes in subclinical ovarian abnormalities in …

Hpv Vaccination Among Females With Mental And Physical Limitation, Melissa Rowe, Audra L. Pritt, Amanda J. Stratton, Jennie L. Yoost

Marshall Journal of Medicine

Introduction

Adolescent HPV vaccination rates lag behind other vaccinations, partly due to missed opportunities for vaccination and lack of provider recommendation. This study evaluated the rates of HPV vaccination among adolescents with physical and mental limitation and controls, and evaluated differences in parental knowledge and reasons for nonvaccination between groups.

Materials and Methods

A retrospective chart review was performed on female patients age 12-18 presenting to pediatric or gynecology clinics in 2012. Those subjects with a diagnosis of mental or physical limitation were classified as “affected”. HPV vaccination rates were compared between affected and control groups. Parents of affected subjects …

Determinants Of Modern Contraceptive Use Among Sexually Active Men In Kenya, Rhoune Ochako, Marleen Temmerman, Mwende Mbondo, Ian Askew

Obstetrics and Gynaecology, East Africa

Background: Research in Kenya has focussed on family planning from women’s perspectives, with the aim of helping reduce the burden of unintended pregnancies. As such, the determinants of modern contraceptive use among sexually active women are well documented. However, the perspectives of men should be considered not only as women’s partners, but also as individuals with distinct reproductive histories and desires of their own. This study seeks to understand the determinants of modern contraceptive use among sexually active men, by exploring factors that are correlated with modern contraceptive use.

Methods: The data source is the nationally representative 2014 Kenya Demographic …

Patient Perspectives On Quality Family Planning Services In Underserved Areas, Debora Goldberg, Bhakthi Sahgal, Tishra Beeson, Susan F. Wood, Holly Mead, Aliyah Abdul-Wakil, Hallie Stevens, Pinyao Rui, Sara Rosenbaum

Patient Experience Journal

Ongoing challenges impede efforts to improve the quality of family planning services in underserved communities, which by definition lack sufficient numbers of physicians and other health professionals. Challenges to improving the quality of family planning services include financing difficulties, lack of standards, training deficiencies, as well as little understanding and attention to patient preferences. The objectives of this study were to explore female patients’ preferences for family planning services in underserved areas and to develop a framework to help providers improve patient-centered care. The methodology for this paper included mixed methods research including a survey of women between the ages …

The Effects Of Continuous Insulin Pump Therapy On Glycemic Control In Pregnant Type 1 Diabetics, Kimberly Kelsey

Scholarly and Creative Works Conference (2015 - 2021)

Type 1 Diabetes Mellitus accounts for approximately 5% of the diabetic population (CDC, 2015). Numerous complications must be avoided when a diabetic is insulin dependent. Women who are diabetic who are planning to conceive a family have special considerations. Little research has been focused into how to best manage Type 1 diabetics during pregnancy. Since Type 1 diabetes is predominantly diagnosed between birth and 30 years of age, many Type 1 diabetics have potential to become pregnant without knowing how to best manage their diabetes. Poor glycemic control in diabetics has been related to miscarriages, stillbirths, malformations, and macrosomia (Lapolla, …

Ten Important Considerations For Ovarian Cancer Screening, Edward J. Pavlik

Obstetrics and Gynecology Faculty Publications

The unique intricacies of ovarian cancer screening and perspectives of different screening methods are presented as ten considerations that are examined. Included in these considerations are: (1) Deciding on the number of individuals to be screened; (2) Anticipating screening group reductions due to death; (3) Deciding on the duration and frequency of screening; (4) Deciding on an appropriate follow-up period after screening; (5) Deciding on time to surgery when malignancy is suspected; (6) Deciding on how screen-detected ovarian cancers are treated and by whom; (7) Deciding on how to treat the data of enrolled participants; (8) Deciding on the most …

Granulosa Cell Endothelin-2 Expression Is Fundamental For Ovulatory Follicle Rupture, Joseph A. Cacioppo, Po-Ching Patrick Lin, Patrick R. Hannon, Daniel R. Mcdougle, Arnon Gal, Chemyong Ko

Obstetrics and Gynecology Faculty Publications

Ovulation is dependent upon numerous factors mediating follicular growth, vascularization, and ultimately oocyte release via follicle rupture. Endothelin-2 (EDN2) is a potent vasoconstrictor that is transiently produced prior to follicle rupture by granulosa cells of periovulatory follicles and induces ovarian contraction. To determine the role of Edn2 expression, surgical transplant and novel conditional knockout mice were super-ovulated and analyzed. Conditional knockout mice utilized a new iCre driven by the Esr2 promoter to selectively remove Edn2. Follicle rupture and fertility were significantly impaired in the absence of ovarian Edn2 expression. When ovaries of Edn2KO mice were transplanted in wild type …

Scientific Evidence For Different Options For Gdm Screening And Management: Controversies And Review Of The Literature., Claudia Caissutti, Vincenzo Berghella

Department of Obstetrics and Gynecology Faculty Papers

Background. Gestational diabetes (GDM) affects up to 7% of pregnant women and is associated with several maternal and perinatal morbidities. International organizations suggest several different recommendations regarding how to screen and to manage GDM. Objective. We aimed to analyze the most important and employed guidelines about screening and management of GDM and we investigated existing related literature. Results. We found several different criteria for screening for GDM, for monitoring GDM, and for starting pharmacological therapy. When using IADPSG criteria, GDM rate increased, perinatal outcomes improved, and screening became cost-effective. Compared to no treatment, treatment of women meeting criteria for GDM …

Plasma Cross-Gestational Sphingolipidomic Analyses Reveal Potential First Trimester Biomarkers Of Preeclampsia, Aneta Dobierzewska, Sony Soman, Sebastian E Illanes, Andrew J. Morris

Saha Cardiovascular Research Center Faculty Publications

Introduction

Preeclampsia (PE) is a gestational disorder, manifested in the second half of pregnancy by maternal hypertension, proteinuria and generalized edema. PE is a major cause of maternal and fetal morbidity and mortality, accounting for nearly 40% of all premature births worldwide. Bioactive sphingolipids are emerging as key molecules involved in etiopathogenesis of PE, characterized by maternal angiogenic imbalance and symptoms of metabolic syndrome. The aim of this study was to compare the cross-gestational profile of circulating bioactive sphingolipids in maternal plasma from preeclamptic (PE) versus normotensive control (CTL) subjects with the goal of identifying sphingolipids as candidate first trimester …

The Rejoice Trial: A Phase 3 Randomized, Controlled Trial Evaluating The Safety And Efficacy Of A Novel Vaginal Estradiol Soft-Gel Capsule For Symptomatic Vulvar And Vaginal Atrophy., Ginger D Constantine, James A Simon, James H Pickar, David F Archer, Harvey Kushner, Brian Bernick, Gina Gasper, Shelli Graham, Sebastian Mirkin

Obstetrics and Gynecology Faculty Publications

OBJECTIVE: To evaluate the safety and efficacy of TX-004HR vaginal estradiol soft-gel capsules for moderate-to-severe dyspareunia associated with postmenopausal vulvar and vaginal atrophy.

METHODS: In this randomized, double-blind, placebo-controlled, phase 3 study, postmenopausal women with a self-identified most bothersome symptom of dyspareunia received 4, 10, or 25 μg TX-004HR or placebo for 12 weeks. Four co-primary efficacy endpoints were change from baseline to week 12 in percentages of superficial and parabasal cells, vaginal pH, and severity of dyspareunia. Secondary endpoints included severity of vaginal dryness and vulvar and/or vaginal itching or irritation. Endometrial histology and adverse events (AEs) were included …

Effect Of Early Tranexamic Acid Administration On Mortality, Hysterectomy, And Other Morbidities In Women With Post-Partum Haemorrhage (Woman): An International, Randomised, Double-Blind, Placebo-Controlled Trial, Haleema Shakur-Still, Ian Roberts, Rizwana Chaudhri, Bukola Fawole, Mohamed El-Sheikh, Adesina L. Akintan, Zahida Qureshi, Hussein Kidanto, Bellington Vwalika, Abdulfetah Abdulkadir

Faculty of Health Sciences, East Africa

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage.

Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition …

The Disappearance Of Nyoman And Ketut, Laura Michelle Garvie

Independent Study Project (ISP) Collection

No abstract provided.

Ovarian Cancer Incidence Corrected For Oophorectomy, Lauren A. Baldwin, Quan Chen, Thomas C. Tucker, Connie G. White, Robert N. Ore, Bin Huang

Obstetrics and Gynecology Faculty Publications

Current reported incidence rates for ovarian cancer may significantly underestimate the true rate because of the inclusion of women in the calculations who are not at risk for ovarian cancer due to prior benign salpingo-oophorectomy (SO). We have considered prior SO to more realistically estimate risk for ovarian cancer. Kentucky Health Claims Data, International Classification of Disease 9 (ICD-9) codes, Current Procedure Terminology (CPT) codes, and Kentucky Behavioral Risk Factor Surveillance System (BRFSS) Data were used to identify women who have undergone SO in Kentucky, and these women were removed from the at-risk pool in order to re-assess incidence rates …

Comparison Of Foeto-Maternal Outcome In Pregnant Women With Hepatitis E - A Review Of 12 Years., Tahira Naru, Farheen Yousuf, Ayesha Malik, Sumaira Naz, Humera Ismail

Department of Obstetrics & Gynaecology

Objective: To compare adverse maternal and foetal outcome in pregnant women with hepatitis E immunoglobulin M reactive versus non-reactive.
Methods: This retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised records of pregnant patients at any gestational age with clinical and biochemical evidence of hepatitis E from January 2002 and December 2014. . Maternal and perinatal outcome of the subjects were analysed. SPSS 20 was used for data analysis.
Results: Out of the 200 subjects, 168(84 %) were hepatitis E immunoglobulin M reactive and 32(16%) were non-reactive. The overall mean age was 26.7±4.5 years. Also, 12(7%) …

A Prospective Study Of Maternal, Fetal And Neonatal Outcomes In The Setting Of Cesarean Section In Low- And Middle-Income Countries., Margo S. Harrison, Omrana Pasha, Sarah Saleem, Sumera Ali, Elwyn Chomba, Waldemar A. Carlo, Ana L. Garces, Nancy F. Krebs, K. Michael Hambidge, Shivaprasad S. Goudar, Bhala Kodkany, Sangappa Dhaded, Richard J. Derman, Archana Patel, Patricia L. Hibberd, Fabian Esamai, Edward A. Liechty, Janet L. Moore, Dennis Wallace, Elizabeth M. Mcclure, Menachem Miodovnik, Marion Koso-Thomas, Jose Belizan, Antoinette K. Tshefu, Melissa Bauserman, Robert L. Goldenberg

Global Health Articles

INTRODUCTION: Cesarean section (CS) rates are increasing globally with an unclear effect on pregnancy outcomes. The study objective was to quantify maternal and perinatal morbidity and mortality associated with CS compared with vaginal delivery (VD) both within and across sites in low- and middle-income countries.

MATERIAL AND METHODS: A prospective population-based study including home and facility births in 337 153 women with a VD and 47 308 women with a CS from 2010 to 2015 was performed in Guatemala, India, Kenya, Pakistan, Zambia and Democratic Republic of Congo. Women were enrolled during pregnancy; delivery and 6-week follow-up data were collected. …

Clinical Significance Of A False Positive Glucose Challenge Test In Patients With A High Body Mass Index, A Borja, M Moretti, Nisha Lakhi

NYMC Faculty Publications

OBJECTIVE: To determine if there is an increased maternal or neonatal morbidity in overweight and obese patients with a false positive glucose challenge test (GCT). METHODS: Patients with a body mass index (BMI) >/=25.0 at registration were included in this prospective 36-month study. The study cohort consisted of patients with a false positive (FP) GCT, with two comparison cohorts: those with a (1) screen negative (SN) GCT result and (2) true positive (TP) GCT result. Risks were reported as odd ratios with 95% confidence intervals, with a P/=4000 g in the FP cohort, but this fell short of reaching statistical …

Identificando Los Limites Del Acceso A La Salud Reproductiva: Un Análisis Sobre Las Experiencias Vividas Por Las Mujeres Guaraníes Con Los Servicios De La Salud Reproductiva En La Villa 31 De Buenos Aires, Amelia Mitchell

Independent Study Project (ISP) Collection

In order to serve the ‘public’, public health services must be accessible to everyone, without discrimination based on race, gender, social class, or geographic location, among other facets of identity. Reproductive health services, in particular, are a key service that must be adequately supplied in order to guarantee the health and wellbeing of a population. Reproductive healthcare not only allows individuals to decide if and when they wish to have a child, it also contributes to cancer prevention and the detrimental effects of sexually transmitted diseases. This investigation examines the experiences of Guaraní women that live within “Villa 31” of …

High-Grade Cervical Dysplasia In Pregnancy – Psychological And Medical Challenges, Denisa O. Balalau, Romina M. Sima, Nicolae Bacalbasa, Petrisor Banu, Cristian Bălălău, Liana Ples, Anca D. Stanescu

Journal of Mind and Medical Sciences

Despite being rare, the incidence of pregnancy-related cancer is expected to rise as women continue to delay childbearing and give birth later in their reproductive years. In this broad category, tumors like breast cancer, dermatological neoplasia and cervical cancer are most common and tend to arise in women of childbearing age. All pregnant women with clinical and cytologic suspicion of cervical cancer, except for squamous atypia or low-grade squamous intraepithelial lesions, should undergo colposcopy, with or without biopsy, the latter being avoided if possible due to possible complications which, although rare, may involve preterm labor initiation.

Some studies have attempted …

Unique Synergistic Formulation Of Curcumin, Epicatechin Gallate And Resveratrol, Tricurin, Suppresses Hpv E6, Eliminates Hpv+ Cancer Cells, And Inhibits Tumor Progression, Sumit Mukherjee, Priya Ranjan Debata, Rahman Hussaini, Kaushiki Chatterjee, Juliet N. E. Baidoo, Samay Sampat, Anita Szerszen, Joseph P. Navarra, Jimmie Fata, Elena Severinova, Probal Banerjee, Mario R. Castellanos

Publications and Research

Curcumin (from curry) (C) is highly potent against cervical cancer cells (CCC), but poor bioavailability has limited its clinical use. Similar natural polyphenols resveratrol (from grapes) (R), and epicatechin gallate (from green tea) (E) also display activity against CCC. By treating CCC (HeLa) with C, E, or R, or combinations of these compounds, we computed combination indices and observed a strong synergism among C, E, and R at the unique molar ratio 4:1:12.5. This combination, named as TriCurin, rapidly down regulated HPV18 E6 and NF-kB expression while concomitantly inducing the tumor suppressor protein p53 in HeLa cells. In the mouse …

Maternal Characteristics And Obstetrical Complications Impact Neonatal Outcomes In Indonesia: A Prospective Study., Trisari Anggondowati, Ayman A E El-Mohandes, S Nurul Qomariyah, Michele Kiely, Judith J Ryon, Reginald F Gipson, Benjamin Zinner, Anhari Achadi, Linda L Wright

Medicine Faculty Publications

BACKGROUND: We investigated associations between maternal characteristics, access to care, and obstetrical complications including near miss status on admission or during hospitalization on perinatal outcomes among Indonesian singletons.

METHODS: We prospectively collected data on inborn singletons at two hospitals in East Java. Data included socio-demographics, reproductive, obstetric and neonatal variables. Reduced multivariable models were constructed. Outcomes of interest included low and very low birthweight (LBW/VLBW), asphyxia and death.

RESULTS: Referral from a care facility was associated with a reduced risk of LBW and VLBW [AOR = 0.28, 95% CI = 0.11-0.69, AOR = 0.18, 95% CI = 0.04-0.75, respectively], stillbirth …

Symptoms Relevant To Surveillance For Ovarian Cancer, Robert M. Ore, Lauren Baldwin, Dylan Woolum, Erika Elliott, Christiaan Wijers, Chieh-Yu Chen, Rachel W. Miller, Christopher P. Desimone, Frederick R. Ueland, Richard J. Kryscio, John R. Van Nagell, Edward J. Pavlik

Obstetrics and Gynecology Faculty Publications

To examine how frequently and confidently healthy women report symptoms during surveillance for ovarian cancer. A symptoms questionnaire was administered to 24,526 women over multiple visits accounting for 70,734 reports. A query of reported confidence was included as a confidence score (CS). Chi square, McNemars test, ANOVA and multivariate analyses were performed. 17,623 women completed the symptoms questionnaire more than one time and > 9500 women completed it more than one four times for > 43,000 serially completed questionnaires. Reporting ovarian cancer symptoms was ~245 higher than ovarian cancer incidence. The positive predictive value (0.073%) for identifying ovarian cancer based on symptoms …

Galactose And Its Metabolites Deteriorate Metaphase Ii Mouse Oocyte Quality And Subsequent Embryo Development By Disrupting The Spindle Structure, Mili Thakur, Faten Shaeib, Sana N. Khan, Hamid-Reza Kohan-Ghader, Roohi Jeelani, Sarah R. Aldhaheri, Bernard Gonik, Husam M. Abu-Soud

C.S. Mott Center Research Publications

Premature ovarian insufficiency (POI) is a frequent long-term complication of classic galactosemia. The majority of women with this disorder develop POI, however rare spontaneous pregnancies have been reported. Here, we evaluate the effect of D-galactose and its metabolites, galactitol and galactose 1-phosphate, on oocyte quality as well as embryo development to elucidate the mechanism through which these compounds mediate oocyte deterioration. Metaphase II mouse oocytes (n=240), with and without cumulus cells (CCs), were exposed for 4hours to D-galactose (2μM), galactitol (11μM) and galactose 1-phosphate (0.1mM), (corresponding to plasma concentrations in patients on galactoserestricted diet) and compared to controls. The treated …

A Perspective On Ovarian Cancer Biomarkers: Past, Present And Yet-To-Come, Frederick R. Ueland

Obstetrics and Gynecology Faculty Publications

The history of biomarkers and ultrasonography dates back over more than 50 years. The present status of biomarkers used in the context of ovarian cancer is addressed. Attention is given to new interpretations of the etiology of ovarian cancer. Cancer antigen 125 (CA125) and multivariate index assays (Ova1, Risk of Ovarian Malignancy Algorithm, Overa) are biomarker-driven considerations that are presented. Integration of biomarkers into ovarian cancer diagnostics and screening are presented in conjunction with ultrasound. Consideration is given to the serial application of both biomarkers and ultrasound, as well as morphology-based indices. Attempts are made to foresee how individualized molecular …

Complications From Surgeries Related To Ovarian Cancer Screening, Lauren A. Baldwin, Edward J. Pavlik, Emma Ueland, Hannah E. Brown, Kelsey M. Ladd, Bin Huang, Christopher P. Desimone, John R. Van Nagell, Frederick R. Ueland, Rachel W. Miller

Obstetrics and Gynecology Faculty Publications

The aim of this study was to evaluate complications of surgical intervention for participants in the Kentucky Ovarian Cancer Screening Program and compare results to those of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial. A retrospective database review included 657 patients who underwent surgery for a positive screen in the Kentucky Ovarian Cancer Screening Program from 1988–2014. Data were abstracted from operative reports, discharge summaries, and office notes for 406 patients. Another 142 patients with incomplete records were interviewed by phone. Complete information was available for 548 patients. Complications were graded using the Clavien–Dindo (C–D) Classification of Surgical …

Twin Chorionicity And Prospective Stillbirth Risk: Experience At A Tertiary Care Hospital, Shazia Masheer, Zaheena Islam, Dhanwanti Dileep, Shama Munim

Department of Obstetrics & Gynaecology

Objective: To determine the prospective risk of stillbirth, perinatal death and neonatal morbidities in twins.

Methods: This retrospective cohort study was conducted at the Aga Khan University Hospital, Karachi, and comprised cases of twin pregnancies from January 2001 to December 2012. . Cases of both monochorionic diamniotic and dichorionic diamniotic twin pregnancies were included. SPSS 19 was used for data analysis.

Results: Of the 394 cases, 84(21.3%) were monochorionic diamniotic twins and 310(78.7%) were dichorionic diamniotic twins. There were no cases of stillbirth beyond 30 and 34 weeks in monochorionic and dichorionic twins, respectively. Neonatal mortality stood reduced beyond 36 …

Reply To The Letter To The Editor, Anthony M. Vintzileos Md, John C. Smulian Md, Mph

Department of Obstetrics & Gynecology

No abstract provided.

Reply To M. Lambertini Et Al, Kutluk Oktay, V Turan, G Bedoschi

NYMC Faculty Publications

No abstract provided.

A Comparison Of Colorimetric Assessment Of Vaginal Ph With Nugent Score For The Detection Of Bacterial Vaginosis., Matthew K. Hoffman, Mrutyunjaya B. Bellad, Umesh S. Charantimath, Avinash Kavi, Jyoti M. Nagmoti, Mahantesh B. Nagmoti, Ashalata A. Mallapur, Geetanjali M. Katageri, Umesh Y. Ramadurg, Sheshidhar G. Bannale, Amit P. Revankar, M. S. Ganachari, Richard J. Derman, Shivaprasad S. Goudar

Department of Obstetrics and Gynecology Faculty Papers

Background. A Nugent score > 7 has been defined as the gold standard for the diagnosis for bacterial vaginosis (BV), though it is resource intensive and impractical as point of care testing. We sought to determine if colorimetric assessment of vaginal pH can accurately predict the occurrence of BV. Methods. We performed a planned subanalysis of 1,216 pregnant women between 13 0/7 and 19 6/7 weeks who underwent vaginal examination as part of a randomized controlled trial. Using a standardized technique, specimens were obtained for colorimetric assessment and two separate slides for Gram staining. These slides were subsequently evaluated by two …