Medicine and Health Sciences Commons^™

Changes In Immunological And Hematological Parameters Of Female Residents Exposed To Volatile Organic Compounds In The City Of Kaohsiung, Taiwan, Hueiwang Anna Jeng, I-Long Lee, Yang-Yen Gau, Ching-Tzu Yang, Chitsan Lin, Yu-Jue Hong

Community & Environmental Health Faculty Publications

The objective of this study was to assess the effects, if any, of volatile organic compounds (VOCs) in the ambient air of Kaohsiuug, Taiwan, on certain hematological and immunological parameters of 153 female study participants. The major source of VOCs was vehicle emissions. The participants were selected from three areas, each area at a different distance from a freeway. Results indicated that total concentrations of VOCs and a subgroup of 25 VOCs (VOC₂₅.) ranged from 250 to 335 ppb and 89 to 113 ppb, respectively. The distribution of VOC concentrations did not correlate with distance from the freeway. …

Pharmacological Studies Of Nicotine And Galantamine Effects On Age Associated Memory Impairment And The Neurotrophic System In Aged Female Rats, Kristen L. French

MUSC Theses and Dissertations

Nicotine and Galantamine were studied for their pharmacological effects on age associated memory impairment (AAMI) and the neurotrophin system in the aged female F344 rat. Nicotine was found to have dose dependent effects on cognition in the 24 month old rat. A low dose of nicotine improved both working and reference memory (WM, RM) performance on the water radial arm maze and also improved the ability of aged rats to handle an increasing WM load. A high dose did not improve WM and caused deficits in RM, and high cotinine levels in these subjects correlated with worse performance. Nicotine treatment …

Classification And Risk Stratification Of Invasive Breast Carcinomas Using A Real-Time Quantitative Rt-Pcr Assay., Laurent Perreard, Cheng Fan, John F Quackenbush, Michael Mullins, Nicholas P Gauthier, Edward Nelson, Mary Mone, Heidi Hansen, Saundra S Buys, Karen Rasmussen, Alejandra Ruiz Orrico, Donna Dreher, Rhonda Walters, Joel Parker, Zhiyuan Hu, Xiaping He, Juan P Palazzo, Olufunmilayo I Olopade, Aniko Szabo, Charles M Perou, Philip S Bernard

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

INTRODUCTION: Predicting the clinical course of breast cancer is often difficult because it is a diverse disease comprised of many biological subtypes. Gene expression profiling by microarray analysis has identified breast cancer signatures that are important for prognosis and treatment. In the current article, we use microarray analysis and a real-time quantitative reverse-transcription (qRT)-PCR assay to risk-stratify breast cancers based on biological 'intrinsic' subtypes and proliferation. METHODS: Gene sets were selected from microarray data to assess proliferation and to classify breast cancers into four different molecular subtypes, designated Luminal, Normal-like, HER2+/ER-, and Basal-like. One-hundred and twenty-three breast samples (117 invasive …

Analysis Of Epstein-Barr Virus Reservoirs In Paired Blood And Breast Cancer Primary Biopsy Specimens By Real Time Pcr., R Serene Perkins, Katherine Sahm, Cindy Marando, Diana Dickson-Witmer, Gregory R Pahnke, Mark Mitchell, Nicholas J Petrelli, Irving M Berkowitz, Patricia Soteropoulos, Virginie M Aris, Stephen P Dunn, Leslie J Krueger

Department of Surgery Faculty Papers

INTRODUCTION: Epstein-Barr virus (EBV) is present in over 90% of the world's population. This infection is considered benign, even though in limited cases EBV is associated with infectious and neoplastic conditions. Over the past decade, the EBV association with breast cancer has been constantly debated. Adding to this clinical and biological uncertainty, different techniques gave contradictory results for the presence of EBV in breast carcinoma specimens. In this study, minor groove binding (MGB)-TaqMan real time PCR was used to detect the presence of EBV DNA in both peripheral blood and tumor samples of selected patients. METHODS: Peripheral blood and breast …

Placental Expression Of Angiopoietin-1, Angiopoietin-2 And Tie-2 During Placental Development In An Ovine Model Of Placental Insufficiency-Fetal Growth Restriction., Amy S Erickson Hagen, Ryan J Orbus, Randall B Wilkening, Timothy Regnault, Russell V Anthony

Paediatrics Publications

Fetal growth restriction (FGR) is associated with increased perinatal morbidity and mortality, and often results from functional placental insufficiency. Placentation requires extensive vasculogenesis and subsequent angiogenesis, in both maternal and fetal tissues. Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) are angiogenic growth factors expressed in the placenta, and compete for binding to a common receptor, Tunica interna endothelial cell kinase-2 (Tie-2). Our objective was to examine Ang-1, Ang-2 and Tie-2 expression in ovine placental tissue obtained from normal and FGR pregnancies throughout gestation. Fetal cotyledon and maternal caruncle tissue concentrations of Ang-1, Ang-2 and Tie-2 mRNA were assessed by real-time reverse transcriptase-polymerase …

Resident Efficiency In A Pediatric Emergency Department., M Denise Dowd, Celeste Tarantino, Theodore M. Barnett, Laura Fitzmaurice, Jane F. Knapp

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To measure the hourly rate of patients evaluated and treated by resident physicians in an academic pediatric emergency department (PED) and examine differences in the rate by subspecialty and year of training.

METHODS: For all residents rotating in an academic, urban children's hospital PED, the rate of patients seen per hour over the course of their rotation was calculated using an electronic tracking system, EmSTAT, for calendar year 2000. Rates are reported as the mean number of patients seen per resident hour worked. Mean differences are reported for resident subspecialties (emergency medicine, pediatrics, and family practice) and postgraduate year …

Near-Infrared Characterization Of Breast Tumors In Vivo Using Spectrally-Constrained Reconstruction, Subhadra Srinivasan, Brian W. Pogue, Ben Brooksby, Shudong Jiang, Hamid Dehghani, Christine Kogel, Wendy A. Wells, Steven P. Poplack, Keith D. Paulsen

Dartmouth Scholarship

Multi-wavelength Near-Infrared (NIR) Tomography was utilized in this study to non-invasively quantify physiological parameters of breast tumors using direct spectral reconstruction. Frequency domain NIR measurements were incorporated with a new spectrally constrained direct chromophore and scattering image reconstruction algorithm, which was validated in simulations and experimental phantoms. Images of total hemoglobin, oxygen saturation, water, and scatter parameters were obtained with higher accuracy than previously reported. Using this spectral approach, in vivo NIR images are presented and interpreted through a series of case studies (n=6 subjects) having differing abnormalities. The corresponding mammograms and ultrasound images are also evaluated. Three of six …

A Drosophila Deg/Enac Channel Subunit Is Required For Male Response To Female Pheromones, Heping Lin, Kevin J. Mann, Elena Starostina, Ronald D. Kinser, Claudio W. Pikielny

Dartmouth Scholarship

Odorants and pheromones as well as sweet- and bitter-tasting small molecules are perceived through activation of G protein-coupled chemosensory receptors. In contrast, gustatory detection of salty and sour tastes may involve direct gating of sodium channels of the DEG/ENaC family by sodium and hydrogen ions, respectively. We have found that ppk25, a Drosophila melanogaster gene encoding a DEG/ENaC channel subunit, is expressed at highest levels in the male appendages responsible for gustatory and olfactory detection of female pheromones: the legs, wings, and antennae. Mutations in the ppk25 gene reduce or even abolish male courtship response to females in the dark, …

Does The Choice Of Bottle Nipple Affect The Oral Feeding Performance Of Very-Low-Birthweight (Vlbw) Infants?

Faculty, Staff and Students Publications

BACKGROUND: There is a continuous debate regarding the best bottle nipple to be used to enhance the bottle-feeding performance of a preterm infant. Aim: To verify that feeding performance can be improved by using the bottle nipple with the physical characteristics that enhance infants' sucking skills. METHODS: Ten "healthy" VLBW infants (941+/-273 g) were recruited. Feeding performance was monitored at two time periods, when taking 1-2 and 6-8 oral feedings/d. At each time and within 24 h, performance was monitored using three different bottle nipples offered in a randomized order. Rate of milk transfer (ml/min) was the primary outcome measure. …

P38 Mitogen-Activated Protein Kinase (Mapk) First Regulates Filamentous Actin At The 8-16-Cell Stage During Preimplantation Development., Andrew J M Paliga, David R Natale, Andrew J Watson

Obstetrics & Gynaecology Publications

BACKGROUND INFORMATION: The MAPK (mitogen-activated protein kinase) superfamily of proteins consists of four separate signalling cascades: the c-Jun N-terminal kinase or stress-activated protein kinases (JNK/SAPK); the ERKs (extracellular-signal-regulated kinases); the ERK5 or big MAPK1; and the p38 MAPK group of protein kinases, all of which are highly conserved. To date, our studies have focused on defining the role of the p38 MAPK pathway during preimplantation development. p38 MAPK regulates actin filament formation through the downstream kinases MAPKAPK2/3 (MAPK-activated protein kinase 2/3) or MAPKAPK5 [PRAK (p38 regulated/activated kinase)] and subsequently through HSP25/27 (heat-shock protein 25/27). We recently reported that 2-cell-stage murine …

The Neural Mechanisms Of Speech Comprehension: Fmri Studies Of Semantic Ambiguity, Jennifer M Rodd, Matthew H Davis, Ingrid Johnsrude

Brain and Mind Institute Researchers' Publications

A number of regions of the temporal and frontal lobes are known to be important for spoken language comprehension, yet we do not have a clear understanding of their functional role(s). In particular, there is considerable disagreement about which brain regions are involved in the semantic aspects of comprehension. Two functional magnetic resonance studies use the phenomenon of semantic ambiguity to identify regions within the fronto-temporal language network that subserve the semantic aspects of spoken language comprehension. Volunteers heard sentences containing ambiguous words (e.g. 'the shell was fired towards the tank') and well-matched low-ambiguity sentences (e.g. 'her secrets were written …

A Critical Role For The Programmed Death Ligand 1 In Fetomaternal Tolerance, Indira Guleria, Arezou Khosroshahi, Mohammed Javeed Ansari, Antje Habicht, Miyuki Azuma, Hideo Yagita, Randolph J. Noelle

Dartmouth Scholarship

Fetal survival during gestation implies that tolerance mechanisms suppress the maternal immune response to paternally inherited alloantigens. Here we show that the inhibitory T cell costimulatory molecule, programmed death ligand 1 (PDL1), has an important role in conferring fetomaternal tolerance in an allogeneic pregnancy model. Blockade of PDL1 signaling during murine pregnancy resulted in increased rejection rates of allogeneic concepti but not syngeneic concepti. Fetal rejection was T cell

Effects Of Estradiol On Lipopolysaccharide And Pam3cys Stimulation Of Ccl20/Macrophage Inflammatory Protein 3 Alpha And Tumor Necrosis Factor Alpha Production By Uterine Epithelial Cells In Culture, Mardi A. Crane-Godreau, Charles R. Wira

Dartmouth Scholarship

We have previously demonstrated that rat uterine epithelial cells (UEC) produce CCL20/macrophage inflammatory protein 3 alpha (MIP3alpha) and tumor necrosis factor alpha (TNF-alpha) in response to live and heat-killed Escherichia coli and to the pathogen-associated molecular patterns (PAMP) lipopolysaccharide (LPS) and Pam3Cys. To determine whether estradiol (E2) modulates PAMP-induced CCL20/MIP3alpha and TNF-alpha secretion, primary cultures of rat UEC were incubated with E2 for 24 h and then treated with LPS or Pam3Cys or not treated for an additional 12 h. E2 inhibited the constitutive secretion of TNF-alpha and CCL20/MIP3alpha into culture media. Interestingly, E2 pretreatment enhanced CCL20/MIP3alpha secretion due to …

A Model Program For Youth Suicide Prevention, Hatim A. Omar

Pediatrics Faculty Publications

Youth suicide continues to be one of the leading causes of death in the United States. Nation wide it is the third leading cause of death in the 10-24 year old age group. The rate of suicide varies somewhat from state to state. In the state of Kentucky, youth suicide is the second leading cause of death. This article describes a grass root, community-based program for youth suicide prevention and its impact on the community. The Stop Youth Suicide Campaign was launched in October 2000 and included more than 30 local agencies. This program worked. through public education, education of …

Stress Levels, Psychological Symptoms, And C-Reactive Protein Levels In Covid-19: A Cross-Sectional Study, Jian Zhang, Wei Li, Hideo Hoshi, Stephen L Mills, Stephen C Massey

Faculty, Staff and Student Publications

The correlation between cholinergic sensitivity and the level of stratification for ganglion cells was examined in the rabbit retina. As examples, we have used ON or OFF alpha ganglion cells and ON/OFF directionally selective (DS) ganglion cells. Nicotine, a cholinergic agonist, depolarized ON/OFF DS ganglion cells and greatly enhanced their firing rates but it had modest excitatory effects on ON or OFF alpha ganglion cells. As previously reported, we conclude that DS ganglion cells are the most sensitive to cholinergic drugs. Confocal imaging showed that ON/OFF DS ganglion cells ramify precisely at the level of the cholinergic amacrine cell dendrites, …

Pathways To Ptsd, Part Ii: Sexually Abused Children, Glenn N Saxe

Faculty, Staff and Students Publications

OBJECTIVE: The goal of this research was to develop and test a prospective model of posttraumatic stress symptoms in sexually abused children that includes pretrauma, trauma, and disclosure-related pathways.

METHOD: At time 1, several measures were used to assess pretrauma variables, trauma variables, and stress reactions upon disclosure for 156 sexually abused children ages 8 to 13 years. At the time 2 follow-up (7 to 36 months following the initial interview), the children were assessed for posttraumatic stress disorder (PTSD) symptoms.

RESULTS: A path analysis involving a series of hierarchically nested ordinary least squares multiple regression analyses indicated three direct …

Investigating The Causes Of Low Birth Weight In Contrasting Ovine Paradigms., J M Wallace, Timothy Regnault, S W Limesand, W W Hay, R V Anthony

Paediatrics Publications

Intrauterine growth restriction (IUGR) still accounts for a large incidence of infant mortality and morbidity worldwide. Many of the circulatory and transport properties of the sheep placenta are similar to those of the human placenta and as such, the pregnant sheep offers an excellent model in which to study the development of IUGR. Two natural models of ovine IUGR are those of hyperthermic exposure during pregnancy, and adolescent overfeeding, also during pregnancy. Both models yield significantly reduced placental weights and an asymmetrically growth-restricted fetus, and display altered maternal hormone concentrations, indicative of an impaired trophoblast capacity. Additionally, impaired placental angiogenesis …

Effect Of Serum And Cumulus Cell Expansion On Marker Gene Transcripts In Bovine Cumulus-Oocyte Complexes During Maturation In Vitro., Michele D Calder, Anita N Caveney, Marc-Andre Sirard, Andrew J Watson

Obstetrics & Gynaecology Publications

OBJECTIVE: To determine the distribution of transcripts encoding the FSH receptor (FSHr), LH receptor (LHr), connexin 43 (Cx43), cyclooxygenase-2 (COX-2), and prostaglandin E(2) receptors 2 and 3 (EP2 and EP3) within bovine cumulus-oocyte complexes (COCs) and denuded oocytes and investigate the influence of gonadotropins, serum, and cumulus cell expansion on the abundance of transcripts encoding these genes.

DESIGN: Prospective controlled animal study.

SETTING: University research laboratory.

PATIENT(S): Animal models for human studies.

INTERVENTION(S): Cumulus-oocyte complexes were treated in culture with serum and gonadotropin-supplemented media to examine the effects to mRNA transcript levels.

MAIN OUTCOME MEASURE(S): Variation in mRNA transcript levels. …

Learning To Like: A Role For Human Orbitofrontal Cortex In Conditioned Reward, Sylvia M L Cox, Alexandre Andrade, Ingrid Johnsrude

Brain and Mind Institute Researchers' Publications

A great deal of human behavior and motivation is based on the intrinsic emotional significance of rewarding or aversive events, as well as on the associations formed between such emotional events and concurrent environmental stimuli. Recent functional neuroimaging studies have implicated the ventral striatum, orbitofrontal cortex (OFC), and amygdala in the representation of reward values and/or in the anticipation of rewarding events. Here, we use functional magnetic resonance imaging to compare brain activation during the presentation of reward with that during presentation of (conditioned) stimuli that have been paired previously with reward. Specifically, we aimed to investigate conditioned reward in …

Clinical Characteristics Of Individuals Using An Online Alcohol Evaluation Program., Daniel Z Lieberman

Psychiatry and Behavioral Sciences Faculty Publications

Access to treatment for substance abuse disorders is limited, and practical strategies are needed to expand opportunities for individuals to receive effective interventions. Automated or semi-automated treatments have shown promise in other disorders. Identifying the characteristics of patients who will be able to benefit from this unconventional approach will increase the likelihood of success. The current study examined 1,297 individuals using an online alcohol evaluation program. Subjects had high scores on the Alcohol Use Disorders Identification Test (AUDIT) and a substantial amount of ambivalence about the possible harm that their drinking caused, but they also had very low levels of …

Role For Akt3/Protein Kinase Bγ In Attainment Of Normal Brain Size, Rachel M. Easton, Han Cho, Kristin Roovers, Diana W. Shineman

Dartmouth Scholarship

Studies of Drosophila and mammals have revealed the importance of insulin signaling through phosphatidylinositol 3-kinase and the serine/threonine kinase Akt/protein kinase B for the regulation of cell, organ, and organismal growth. In mammals, three highly conserved proteins, Akt1, Akt2, and Akt3, comprise the Akt family, of which the first two are required for normal growth and metabolism, respectively. Here we address the function of Akt3. Like Akt1, Akt3 is not required for the maintenance of normal carbohydrate metabolism but is essential for the attainment of normal organ size. However, in contrast to Akt1^−/− mice, which display a …

Surgical Images: Soft Tissue. Incarcerated Gallbladder In A Parastomal Hernia., Shawn D. St Peter, Jacques Heppell

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

A Pilot Randomized, Controlled Trial Of An In-Home Drinking Water Intervention Among Hiv + Persons, John M. Colford, Sona R. Saha, Timothy J. Wade, Catherine C. Wright, Mai Vu, Sandra Charles, Peter Jensen, Alan Hubbard, Deborah A. Levy, Joseph N. S. Eisenberg

Journal Articles: Epidemiology

Although immunocompromised persons may be at increased risk for gastrointestinal illnesses, no trials investigating drinking water treatment and gastrointestinal illness in such patients have been published. Earlier results from San Francisco suggested an association (OR 6.76) between tap water and cryptosporidiosis among HIV + persons. The authors conducted a randomized, triple-blinded intervention trial of home water treatment in San Francisco, California, from April 2000 to May 2001. Fifty HIV-positive patients were randomized to externally identical active (N = 24) or sham (N = 26) treatment devices. The active device contained a filter and UV light; the sham provided no treatment. …

A Randomized, Controlled Trial Of In-Home Drinking Water Intervention To Reduce Gastrointestinal Illness, John M. Colford, Timothy J. Wade, Sukhminder K. Sandhu, Catherine C. Wright, Sherline Lee, Susan Shaw, Kim Fox, Susan Burns, Anne Benker, M. Alan Brookhart, Mark Van Der Laan, Deborah A. Levy

Journal Articles: Epidemiology

Trials have provided conflicting estimates of the risk of gastrointestinal illness attributable to tap water. To estimate this risk in an Iowa community with a well-run water utility with microbiologically challenged source water, the authors of this 2000-2002 study randomly assigned blinded volunteers to use externally identical devices (active device: 227 households with 646 persons; sham device: 229 households with 650 persons) for 6 months (cycle A). Each group then switched to the opposite device for 6 months (cycle B). The active device contained a 1-microm absolute ceramic filter and used ultraviolet light. Episodes of "highly credible gastrointestinal illness," a …

Prevalence Of Obesity And Lack Of Physical Activity Among Kentucky Adolescents, Hatim A. Omar, Kristin Rager

Pediatrics Faculty Publications

Lack of physical activity and overweight status continues to be a significant health problem in the United States. To assess the actual prevalence of these problems, we reviewed data from the School-based Health Promotion Centers in one middle school, and one High school in central Kentucky. A total of 232 6th graders and 607 9th graders were included. A total of 92% of 6th graders and 45% of 9th graders reported complete lack of regular exercise. 37% of 9th graders and 59% of 6th graders had inappropriate nutrition, 47% of 9th graders and 33% of 6th graders had Body Mass …

Predicting Childhood Sexual Or Physical Abuse: A Logistic Regression Geo-Mapping Approach To Prevention, Roland K. Tadoum, Kamila Smolij, Michelle A. Lyn, Craig W. Johnson

Faculty, Staff and Student Publications

This study investigates the degree to which gender, ethnicity, relationship to perpetrator, and geomapped socio-economic factors significantly predict the incidence of childhood sexual abuse, physical abuse and non- abuse. These variables are then linked to geographic identifiers using geographic information system (GIS) technology to develop a geo-mapping framework for child sexual and physical abuse prevention.

The Incidence And Prevalance Of Cervical Cancer In Vietnamese Women (1993-1995): A Analysis Of Seer Reported Cases, Thuy Do

Theses and Dissertations

Background: Cervical cancer is the third most common reproductive cancer in the U.S. To date, one report concluded that U.S. Vietnamese women had the highest incidence rate (43.0/100,000). The current study examines whether U.S. Vietnamese women are more likely to have cervical cancer in comparison to Whites, Blacks, Hispanics, American Indians, and other Asian subgroups. Methods: SEER data of cervical cancers diagnosed from 1993-1995 (n = 37,790) was utilized. Using SPSS, chi-square statistics assessed whether Vietnamese women were older and more likely to be married or diagnosed at a later stage. Logistic regression assessed the amount of risk race/ethnicity contributes …

Ccl20/Macrophage Inflammatory Protein 3Α And Tumor Necrosis Factor Alpha Production By Primary Uterine Epithelial Cells In Response To Treatment With Lipopolysaccharide Or Pam3cys, M. A. Crane-Godreau, C. R. Wira

Dartmouth Scholarship

Having previously shown that CCL20/macrophage inflammatory protein 3 and tumor necrosis factor alpha (TNF-alpha) are released by polarized primary rat uterine epithelial cells (UEC) in response to Escherichia coli but not to Lactobacillus rhamnosus , we sought to determine if epithelial cells are responsive to pathogen-associated molecular patterns (PAMP), including lipopolysaccharide (LPS), lipoteichoic acid (LTA), and Pam 3 Cys, a bacterial lipoprotein analog. Epithelial cells were grown to confluence on Nunc cell culture inserts prior to apical treatment with PAMPs. In response to LPS, LTA, and Pam 3 Cys (EMC Microcollection GmbH, Tu ̈- bingen, Germany), CCL20 levels increased (4- …

Medical Symptoms Associated With Tobacco Smoking With And Without Marijuana Abuse Among Crack Cocaine-Dependent Patients., Ashwin A. Patkar, Vikas Batra, Paolo Mannelli, Sarah Evers-Casey, Michael J. Vergare, Frank T. Leone

Department of Psychiatry and Human Behavior Faculty Papers

Despite the widespread use of tobacco and marijuana by cocaine abusers, it remains unclear whether combined tobacco and marijuana smoking is more harmful than tobacco smoking alone in cocaine abusers. We investigated the differences in medical symptoms reported among 34 crack cocaine abusers who did not smoke tobacco or marijuana (C), 86 crack cocaine abusers who also smoked tobacco (C + T), and 48 crack abusers who smoked both tobacco and marijuana (C + T + M). Medical symptoms were recorded using a 134-item self-report instrument (MILCOM), and drug use was assessed using the Addiction Severity Index (ASI). After controlling …

Palm Is Expressed In Both Developing And Adult Mouse Lens And Retina., Meryl Castellini, Louise V Wolf, Bharesh K Chauhan, Deni S Galileo, Manfred W Kilimann, Ales Cvekl, Melinda K Duncan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Paralemmin (Palm) is a prenyl-palmitoyl anchored membrane protein that can drive membrane and process formation in neurons. Earlier studies have shown brain preferred Palm expression, although this protein is a major water insoluble protein in chicken lens fiber cells and the Palm gene may be regulated by Pax6. METHODS: The expression profile of Palm protein in the embryonic, newborn and adult mouse eye as well as dissociated retinal neurons was determined by confocal immunofluorescence. The relative mRNA levels of Palm, Palmdelphin (PalmD) and paralemmin2 (Palm2) in the lens and retina were determined by real time rt-PCR. RESULTS: In the …