7 research outputs found
Outside the doll's house : a study in images of women in English and French theatre, 1848-1914
No full textThe aim of the thesis is to document images of women in English and French
theatre, between 1848 and 1914, which challenged the stereotypical image of women
as passive wives and mothers in the'doll's house!
The methodologies employed are not restricted to dramatic criticism, but draw
upon a udder net of feminism, semiotics, and social history, in order to place the
plays, roles and actresses in the theatre of their time. As a comparative study,
it documents interchange, interaction and difference, between the theatre of England
and France.
The images are divided into three groups, viz., the 'female outcast', the 'third
sex' and 'revolting women'. Section one documents a range of femme fatale images,
including the courtisane; the Magdalen; Cleopatra, the royal seducer: Medea, the
outcast queen, and the dangerous women of melodrama.
The second section begins with studies of the male impersonators of music
hall, notably Vesta Tilley, and the principal boys of Victorian and Edwardian pantomime.
Male impersonation on the 'serious' stage is then considered, in a study of actresses
in the cross-dressing role of Shakespeare's Rosalind, and Bernhardt's travesti roles,
in particular her Hamlet.
The third section considers the révolt6e of the social drama, and debate
surrounding the rationale of motherhood, and the hostile reactions to the issues
of abortion and infanticide. A chapter on Manchester's Gaiety theatre indicates
the importance of the 'new theatres' in providing a udder and more realistic, representation
of women, while the final study examines drama which portrayed the difficulties
for women trying to survive independently of men, indicating the economic disadvantages
and prejudices which drove many women into prostitution.
Overall, the three groups of images represent three strategies for power and
their success and failure is indicated and assessed. The capacity of theatre for
social debate is highlighted, and the contribution of women in the creation of radical
images is re-evaluated, thereby making a significant contribution to women's studies
and to nineteenth century theatre studies
Review for Religious - Issue 49.2 (March/April 1990)
No full textIssue 49.2 of the Review for Religious, March/April 1990.Religious Life Spirituality
The Clericalization of Monasticism
=Thomas Merton and the Enneagram
Directing the Third Week
Volume 49
Number 2
March/April 1990
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©1990 REview For REI,IGIOUS.
David L. Fleming, S.J.
Iris Ann Ledden, S.S.N.D.
Richard A. Hill, S.J.
Jean Read
Mary Ann Foppe
Editor
Associate Editor
Contributing Editor
Assistant Editors
Advisory Board
David J. Hassel, S.J. Sean Sammon, F.M.S.
Mary Margaret Johanning, S.S.N.D. Wendy Wright, Ph.D.
Suzanne Zuercher, O.S.B.
March/April 1990
Volume 49
Number 2
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PRISMS ...
The desire for new life, new ideas, new expressions, new insights
permeates the everyday existence of us all. Modern day advertising and
the consumer economy of first world countries continuously search out
the ways to sell products, not in terms of real needs, but in terms of in-duced
needs for something new. Consumerism builds upon the human
desire for the new, while at the same time offsetting the equally strong
human tendency to remain comfortably entrenched in the familiar.
The Church seasons of Lent and Easter confront us all with our de-sires
for the new and with our equally strong tendency to remain firmly
entrenched where we are. The dialogue between Nicodemus and Jesus
in the third chapter of St. John’s Gospel captures well the continuing ex-change
between the Christian and God, clearly focused during these
Church seasons. Approaching God out of a certain darkness in our lives,
we seek new life and new growth, a new understanding of our faith, or
a new sense of relationship with God and with neighbor. But when God
starts indicating a dying to some familiar life patterns, when God starts
pointing the way to "being born anew," we are tempted to laugh it .off,
to claim we are "too old" to need that kind of change. Why not a little
"renewal," perhaps a little "restoration," or maybe even an attempt
to "recapture" past devotion or past grace (charism)? Any of these
words seem to allow ias to keep some measure of control, to retain some-thing
of the old and familiar, and yet to pray and give God a place.
Rebirth--to be born anew--remains the challenge of Lent and Eas-ter.
Rebirth means the dying and rising--the pattern of the paschal mys-tery-
which we Christians celebrate in the daily Eucharist. More clearly
in these Lenten and Easter seasons we come face-to-face with the most
traditional faith concept--that it is the Spirit who brings to birth and who
gives life, in our continuing personal growth in our life-in-Christ, in the
life of our religious congregations, and in the life of our Church both lo-cal
and larger.
Our personal response to being born anew is taken up in the articles
"Directing the Third Week" by Joseph P. Cassidy, S.J. and "The
Theme of Joy in the Spiritual Exercises" by Joan Mueller, O.S.F. We
are given new insight into our call and our response to new life in the
articles "Will the Real Prodigal Son Please Stand Up?" by Christine Ere-iser,
O.S.B. and "Redemption and Romantic Melancholy: Thomas Mer-ton
and the Enneagram" by Suzanne Zuercher, O.S.B. "The Re-demption
Kernel" by Dennis J. Billy, C.SS.R., presents a new theologi-cal
approach in understanding dying and rising, with special application
161
169 / Review for Religious, March-April 1990
to religious life. Robert T. Sears, S.J., in his article "Resurrection Spiri-tuality
and Healing the Earth," expands our vision about Jesus’ resur-rection
affecting the ecology of our whole world andso giving us the re-sponsibility
of a new life-healing power.
Finally those articles specifically dealing with renewal and transfor-mation
in the congregations of women and men religious indicate the ar-eas
of present struggle, the history of a sometimes laborious develop-ment,
and the proposed costly future of new life. The various authors--
Stephen Tutas, S.M., Charles Reutemann, F.S.C., Anne O’Brien, gsic,
and Lora Ann Quinofiez, C.D.Po and Mary Daniel Turner, S.N.D., de
N.--invite us into seeing and knowing a life beyond renewal and trans-formation,
a birth which only the Spirit can bring about for the future
of religious life.
May the joy with which the risen Jesus consoles us now become
more richly our experience of new life.
David L. Fleming, S.J.
Resurrection Spirituality and
Healing the Earth
Robert T. Sears, S.J.
Father Robert Sears, S.J., teaches in the Institute of Pastoral Studies at Loyola Uni-versity
in Chicago. This article had its origin in a presentation made to the North
American Conference for Christianity and Ecology. His address is 5554 S. Wood-lawn
Avenue; Chicago, Illinois 60637.
Those involved in ecology and those involved in a healing ministry are
for the most part on two different tracks. The one is focused on a scien-tific
study of evolution and the interdependence of creation, the other on
individual hurts with little attention to environment. My own healing min-istry,
on the other hand, has led me little by little to concern for the en-vironment.
I began with attention on the individual, then was led to see
family relationships into past generations as grounding present destruc-tive
patterns. And only recently have I become aware that the environ-ment
itself is affected by these destructive patterns and needs healing.
Several experiences have brought me to this conclusion.
In the first place, there is evidence that places are affected by what
occurs on them. Barbara Shlemon, noted for her healing ministry, has
observed the ongoing destructive influence violence can have on certain
places. She felt called to build a healing center in Clearwater, Florida
but over a year’s time could not find a place. With two others she prayed
for guidance and one member thought of Native Americans. They looked
into the history of that region and found that it was the location of a war
with the Seminole Indians where it is estimated that some 10,000 to
15,000 Seminole Indians died as we took their land. They had a service
of reconciliation, asking forgiveness of the Indians for what our ances-tors
did then. The very next day an ideal piece of land opened up for
163
"164 / Review for Religious, March-April 1990
them! It was as though God would not give the land till reparation was
made for that violence. I will speak later of an instance in my experi-ence
from Chicago. The civil war Camp Douglas lay between Thirty-first
and Thirty-third streets and Cottage Grove. Some 6000 Confeder-ate
soldiers died there in inhuman conditions, and when we went there
to pray for healing, we found that prime property still overgrown and in
ruins.
Secondly, we have some experimental evidence that plants at least
remember. Cleve Backster, an expert on the psychogalvanic skin re-sponse
that is basic to the lie detector, decided one day to attach the elec-trodes
to a tropical plant in his office. ~ He wondered if the plant would
respond to cutting it. It did, but not as much as he expected. He then
thought he would burn its leaves, and even at the thought the graph
showed a violent response. The plant seemed to be able to anticipate his
intended violence. He then set up a situation where plants could "wit-ness"
a destructive action. Six people were selected and given numbers.
All but one were instructed on their paper to go into the room, look at
the plants, and leave. One was instructed to tear up and stamp on one
of two plants in the room and then leave. Electrodes were attached to
the remaining "witness" plant, and each person again went into the
room. Only the plant "knew" who was responsible! There was no re-sponse
for the five innocent persons, but when the culprit went into the
room the plant responded vigorously, as if in fear. It seems to have re-membered.
2
Finally, Dr. Kenneth McAII, an English psychiatrist noted for his heal-ing
ministry with family systems, was traveling by banana boat over the
Bermuda Triangle (a place formed by an imaginary line between Miami,
Puerto Rico, and Bermuda where for hundreds of years ships and aircraft
had gone down without a trace) when the boat was caught in a terrible
storm.3 In escaping south, one of the ship’s boilers broke leaving them
adrift. In his quiet leisure, he heard a droning outside. It wasn’t the crew.
Researching, he found that this was the place unfit slaves were thrown
overboard so their owners could collect insurance money. As Genesis 4
said of Cain’s killing Abel "Your brother’s blood cries out to me from
the soil," these souls were crying out from the sea. On returning to En-gland,
Dr. McAI! got Anglican bishops in various places to celebrate
Eucharist for those who lost their lives in an untimely way in that place,
and later the Bermuda Anglican bishop did the same. For five years be-tween
that celebration (in 1977) and his book (1982), there had been no
reported accident in that region.
Resurrection Spirituality
We are dealing with incidents that are hard to repeat scientifically,
but such evidence supports a view of the world as living and responsive
to what occurs on it. Much like humans who are God’s most developed
creatures, the earth seems to be marked by past experience. Can it be
healed? What implications might result for the earth if humans under-stood
how to assist in this healing? It is my conviction that a deeper un-derstanding
of the resurrection of Jesus would help us bring healing not
only to humans but also to the earth. I will begin by relating creation-centered
spirituality to a focus on resurrection.
Resurrection-Centered Spirituality
A recent focus on the importance of celebrating creation and joining
its creative impulse is the work of Matthew Fox: Creation-centered spiri-tuality
(see his Original Blessing: a Primer in Creation SpiritualiO, (Bear
& Co. Inc., 1983). Fox sees traditional spirituality (which he terms Fall/
Redemption spirituality as instanced in Augustine, Thomas h Kempis
up to Tanqueray) as dualistic, focused on the danger of sensuality and
earthiness and on the need for ascetical restraint. He argues for another
tradition which he finds in the Yahwist, wisdom writers, lrenaeus, Eck-hart
up to Teilhard de Chardin, which is basically positive toward crea-tion.
In his view Fall/Redemption spirituality sees little value in science,
focuses on original sin and its effects, encourages detachment from the
world and moral self-control and awaits the end of the world rather than
its transformation. Creation spirituality, on the other hand, welcomes the
discoveries of science as revealing the creator, focuses on the blessing
of creation and our God-given commission to care for it, moves beyond
moralistic negation of human action to a sense of communion with na-ture,
and believes in the ultimate goodness and creativity of the cosmos.
He wants to move beyond a focus on guilt to a focus on spiritual growth.
He presents four stages from the work of Eckhart: befriending creation,
befriending darkness, befriending creativity or our inner divinity, and be-friending
new creation and universal compassion. I found myself in tune
with those goals, but not with Fox’s negation of the Fall/Redemption tra-dition.
It gradually dawned on me that those very goals are restored to
us through the resurrection of Jesus. Let me explain.
It was Teilhard who turned our attention first to many of these
themes. When he was in the novitiate, he told his director about his de-sire
for both spirituality and science, and his wise novice director encour-aged
him to pursue both, believing that God would somehow bring them
into unity. His focus on evolutign did make theologians suspicious that
he was neglecting original sin. In response he wrote an appendix to The
166 / Review for Religious, March-April 1990
Phenomenon of Man explaining that evil was discoverable at every level
of evolution, even though he chose not to speak of it for the sake of clar-ity,
There is the evil of failure and disorder in adjusting and emerging,
the evil of decomposition of the present to make room for the new, the
evil of solitude and anxiety (especially for humans) in striving for con-sciousness
in a dark universe, and the evil of growth itself--the constant
struggle to make progress against the inertia and resistance of the pre-sent
state. Whether further there is an excess of evil, stemming from an
historic tragedy, he declines in that study to say. What he does persua-sively
illustrate is that humans emerge as a higher consciousness within
an evolving universe filled with seeds of new creation. We must choose,
and in choosing we bring creation with us for better or worse. By our
choices we develop a human "layer" of evolution, a noosphere, that af-fects
everything. We create culture and "history," and we, in turn, are
influenced by that history. We need only look at our technological world
which drives our days with given hours and our attention with narrowly
determined tasks to see how we are formed and informed by our crea-tions.
Yes we are faced with new possibilities and creative challenges,
but new creation is conditioned by the patterns we have grown accus-tomed
to: our compulsion to consume and to live by an ever increasing
standard of consumption. What will empower us to change?
It is this awareness of historical conditioning that makes me take
more seriously than Fox seems to the doctrine of original sin. Granted
the doctrine as developed by Augustine needs reconsideration, still its
roots are the biblical insight that our evil choices have a history. It is not
enough to change our present attitudes because the present is conditioned
by the choices made in our past. Our ancestors need healing and the earth
affected by our ancestors needs healing. Joy in creation cannot accom-plish
the earth’s healing alone. We need redemption, yet a redemption
that does not separate us from the earth but empowers us to purify the
earth and bring it into wholeness. Redemption must be more than per-sonal.
It must extend to the whole of creation. The resurrection of Jesus
changed his sinful, unreliable disciples into a powerful community of com-passion.
Can we expand our view of the resurrection to include its power
to restore the earth? Let us see.
Stages of Salvation History
Both Freud and Jung worked on the assumption that the growth of
the individual in a speeded up way goes through the stages of evolution--
from emergence out of water to the unfolding of human physical and psy-chological
life. This evolutionary view need not be seen as contrary to
Resurrection Spirituality/167
creation, since God’s creativity is always required. It simply describes
how God creates. What I have found is that human spiritual growth also
recapitulates the stages of salvation history, and it is only in light of sal-vation
history that the resurrection as its culmination can be fully under-stood.
I have found five such stages culminating in the death/resurrec-tion
of Jesus as the goal of the process: initial faith (Yahwist), familial
faith (Elohist/Deuteronomist), individuating faith (Exilic prophets and
Job), communitarian faith (foreseen in Isaiah 53, first lived in Jesus) and
mission faith (revealed in Pentecost).4
Let us begin with individuating faith. Ezekiel 18 cites the saying:
"You have heard it said that the fathers have eaten sour grapes and the
children’s teeth are set on edge." It then goes on to say: "That will no
longer be said in Israel, for the children are mine as well as the fathers."
They had been living by a so-called "conditional covenant" that af-firmed:
"if you keep my law, then you will be my people." That cove-nant,
Yahweh affirms, they have broken (see also Jr 31:32), and it is ab-rogated.
Yet in this breakdown there is a breakthrough of a promised
"new covenant" when Yahweh says: "I will put my Spirit within you
and make you live by my statutes" (Ez 36:27). lndividuating faith, then,
is a breakdown of human effort and a turning of each individual to God’s
initiative. I experienced this personally through a period of depression
while studying theology in Germany. I began studying Freud to get some
understanding, but was still depressed. Then one author led me to Isaiah
43:18 (written during the Exile): "remember not the events of the past
¯ . . See I am doing something new." In other words, healing would
come from God’s present creativity, not from my efforts to re.pair the
past.
From that central breakthrough (Israel’s and my own), I saw that
mere keeping the law (familial faith) was no longer enough. In that stage
"The sins of the fathers/mothers are handed down to four generations
(and more in my experience), the blessings to a thousand" (see Dt 5:9f,
Ex 20:5-6 and so forth). In other words the patterns of history are handed
down for better or worse till there is a collapse of human efforts and an
inbreaking of God’s new creation. Even before that concentration on hu-man
cooperation through law, there is (in the Yahwist, Gn 2-3, 12:1-5
and others who wrote in the time of David) a focus on trusting Yahweh
in order to find life. That universal trust, however, gave rise to intermar-riage
and distortion of faith in Yahweh (as it can do whenever we lose
the specificity of our faith) and so encountered the prophetic challenge
of the Elohist and Deuteronomist. We see the result of even this human
"161~ / Review for Religious, March-April 1990
effort in their Exile.
Once we turn to Yahweh’s spirit ourselves, we need to find the spirit
in others. This we do by the forgiveness of enemies which I believe we
find first only in the ministry of Jesus, though it was foreseen and for-gotten
in Isaiah 53--the suffering servant. This stage of unconditional
forgiveness allows us to remain faithful even to unfaithful partners (as
Jesus did with Israel) and so to die that others might live. It forms the
basis for the compassionate community that Matthew Fox envisioned.
And finally, the actual gift of life in union with God releases a new
communal reality through the Pentecostal power of the Spirit. Through
the Spirit Jesus’ death/resurrection builds a living, self-giving commu-nity
that is open to all and to all creation. I contend that it is through this
transformation of humanity that ultimately the earth itself will be trans-formed.
The ground and goal of this development is God who raised Christ
from the dead. The norm of who God is is not creation alone, but the
life/death and resurrection of Jesus. "Who sees me sees the Father" (Jn
14:9). God’s suffering love surrendered his own Son for us, and through
Jesus’ response of self-surrender the Spirit of self-giving love is sent and
revealed. God is revealed as a community of self-giving love in this world-forming
event.
This pattern of stages is fully revealed in Jesus, but is lived out cy-clically.
Individually or communally we can have a breakthrough to a
new stage but then regress to a previous stage. This, I believe, is what
happened in the Church. With the failure to convert Israel, the message
of Christ went to the gentiles who were not prepared with the solidarity
of a thousand year history. The gifts of the Spirit led to factions as we
see in the Corinthian community and in the Didache. The central gift of
the Spirit of forgiving love that builds the self-giving community was su-perseded
by the need for institution and discipline (my "familial
stage"). Structure and control replaced healing as focus of attention. As
in Jesus’ time, I believe we are again emerging from the familial stage
of development to recognize again our need for forgiveness and healing.
Healing the Human Family
In order to understand the healing brought by the resurrection, we
need to look at sin in history. The Yahwist, who first wrote of the sin
of our original ancestors, did so by first looking at the sin of his day (the
time of David). It was a time of domination and exploitation, of loss of
faith in Yahweh because of the multiple marriages of kings like Solo-mon,
of alienation of families torn by strife. If Yahweh was all good,
Resurrection Spirituality 169
how could this happen? The Yahwist concluded (see Gn 2-3) that ~t was
due to a freely chosen loss of faith in Yahweh. Humans were the culmi-nation
of Yahweh’s creation, formed from the earth, given the power to
name (and so direct) creation and the commission to subdue the earth and
bring it to order. All creation served humans, as humans served God. But
they chose their own way and not only did they hide from Yahweh, b
International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways
No full textPrimary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist
Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA response score
No full textBACKGROUND:
Treatment guidelines recommend a stepwise approach to primary biliary cholangitis: all patients begin treatment with ursodeoxycholic acid (UDCA) monotherapy and those with an inadequate biochemical response after 12 months are subsequently considered for second-line therapies. However, as a result, patients at the highest risk can wait the longest for effective treatment. We determined whether UDCA response can be accurately predicted using pretreatment clinical parameters.
METHODS:
We did logistic regression analysis of pretreatment variables in a discovery cohort of patients in the UK with primary biliary cholangitis to derive the best-fitting model of UDCA response, defined as alkaline phosphatase less than 1·67 times the upper limit of normal (ULN), measured after 12 months of treatment with UDCA. We validated the model in an external cohort of patients with primary biliary cholangitis and treated with UDCA in Italy. Additionally, we assessed correlations between model predictions and key histological features, such as biliary injury and fibrosis, on liver biopsy samples.
FINDINGS:
2703 participants diagnosed with primary biliary cholangitis between Jan 1, 1998, and May 31, 2015, were included in the UK-PBC cohort for derivation of the model. The following pretreatment parameters were associated with lower probability of UDCA response: higher alkaline phosphatase concentration (p<0·0001), higher total bilirubin concentration (p=0·0003), lower aminotransferase concentration (p=0·0012), younger age (p<0·0001), longer interval from diagnosis to the start of UDCA treatment (treatment time lag, p<0·0001), and worsening of alkaline phosphatase concentration from diagnosis (p<0·0001). Based on these variables, we derived a predictive score of UDCA response. In the external validation cohort, 460 patients diagnosed with primary biliary cholangitis were treated with UDCA, with follow-up data until May 31, 2016. In this validation cohort, the area under the receiver operating characteristic curve for the score was 0·83 (95% CI 0·79-0·87). In 20 liver biopsy samples from patients with primary biliary cholangitis, the UDCA response score was associated with ductular reaction (r=-0·556, p=0·0130) and intermediate hepatocytes (probability of response was 0·90 if intermediate hepatocytes were absent vs 0·51 if present).
INTERPRETATION:
We have derived and externally validated a model based on pretreatment variables that accurately predicts UDCA response. Association with histological features provides face validity. This model provides a basis to explore alternative approaches to treatment stratification in patients with primary biliary cholangitis.
FUNDING:
UK Medical Research Council and University of Milan-Bicocca
Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA Response Score
No full textBackground: Treatment guidelines recommend a stepwise approach to primary biliary cholangitis: all patients begin treatment with ursodeoxycholic acid (UDCA) monotherapy and those with an inadequate biochemical response after 12 months are subsequently considered for second-line therapies. However, as a result, patients at the highest risk can wait the longest for effective treatment. We determined whether UDCA response can be accurately predicted using pretreatment clinical parameters. Methods: We did logistic regression analysis of pretreatment variables in a discovery cohort of patients in the UK with primary biliary cholangitis to derive the best-fitting model of UDCA response, defined as alkaline phosphatase less than 1·67 times the upper limit of normal (ULN), measured after 12 months of treatment with UDCA. We validated the model in an external cohort of patients with primary biliary cholangitis and treated with UDCA in Italy. Additionally, we assessed correlations between model predictions and key histological features, such as biliary injury and fibrosis, on liver biopsy samples. Findings: 2703 participants diagnosed with primary biliary cholangitis between Jan 1, 1998, and May 31, 2015, were included in the UK-PBC cohort for derivation of the model. The following pretreatment parameters were associated with lower probability of UDCA response: higher alkaline phosphatase concentration (p<0·0001), higher total bilirubin concentration (p=0·0003), lower aminotransferase concentration (p=0·0012), younger age (p<0·0001), longer interval from diagnosis to the start of UDCA treatment (treatment time lag, p<0·0001), and worsening of alkaline phosphatase concentration from diagnosis (p<0·0001). Based on these variables, we derived a predictive score of UDCA response. In the external validation cohort, 460 patients diagnosed with primary biliary cholangitis were treated with UDCA, with follow-up data until May 31, 2016. In this validation cohort, the area under the receiver operating characteristic curve for the score was 0·83 (95% CI 0·79–0·87). In 20 liver biopsy samples from patients with primary biliary cholangitis, the UDCA response score was associated with ductular reaction (r=–0·556, p=0·0130) and intermediate hepatocytes (probability of response was 0·90 if intermediate hepatocytes were absent vs 0·51 if present). Interpretation: We have derived and externally validated a model based on pretreatment variables that accurately predicts UDCA response. Association with histological features provides face validity. This model provides a basis to explore alternative approaches to treatment stratification in patients with primary biliary cholangitis. Funding: UK Medical Research Council and University of Milan-Bicocca
X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis
No full textBACKGROUND & AIMS: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease.METHODS: We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals).RESULTS: Single-marker association analyses found approximately 100 loci displaying P < 5* 10-4, with the most significant being a signal within the OTUD5 gene (rs3027490; P= 4.80* 10-6; odds ratio [OR], 1.39; 95% confidence interval [CI], 1.028-1.88; Japanese cohort). Although the transethnic meta-analysis evidenced only a suggestive signal (rs2239452, mapping within the PIM2 gene; OR, 1.17; 95% CI, 1.09-1.26; P= 9.93* 10-8), the population-specific meta-analysis showed a genome-wide significant locus in East Asian individuals pointing to the same region (rs7059064, mapping within the GRIPAP1 gene; P= 6.2* 10-9; OR, 1.33; 95% CI, 1.21-1.46). Indeed, rs7059064 tags a unique linkage disequilibrium block including 7 genes: TIMM17B, PQBP1, PIM2, SLC35A2, OTUD5, KCND1, and GRIPAP1, as well as a superenhancer (GH0XJ048933 within OTUD5) targeting all these genes. GH0XJ048933 is also predicted to target FOXP3, the main T-regulatory cell lineage specification factor. Consistently, OTUD5 and FOXP3 RNA levels were up-regulated in PBCcase patients (1.75- and 1.64-fold, respectively).CONCLUSIONS: This work represents the first comprehensive study, to our knowledge, of the chrX contribution to the genetics of an autoimmune liver disease and shows a novel PBC-related genome-wide significant locus
Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial
No full textBackgroundEmergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients.MethodsStepped-wedge cluster randomised trial of patients aged ≥40 years undergoing emergency open major abdominal surgery. Hospitals were organised into 15 geographical clusters and commenced the QI programme in random order, based on a computer generated random sequence, over an 85-week period. The trial included an ethnographic study in six hospitals. The primary outcome measure was mortality within 90 days of surgery. Analyses were performed on an intention-to-treat basis. The primary outcome was analysed using a mixed-effects parametric survival model, adjusting for time-related effects.FindingsOf 15,873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. The primary outcome occurred in 1393 patients in the usual care group (16%) compared with 1210 patients in the QI group (16%) (HR QI vs usual care: 1.11 [0.96-1.28]). There were only modest overall improvements in processes of patient care following QI implementation. The ethnographic study revealed good QI engagement but limited time and resources to implement change, affecting which processes teams addressed, the rate of change and eventual success.InterpretationThere was no survival benefit from a QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. The success of the QI intervention may have been limited by the time and resources needed to improve patient care.FundingNational Institute for Health Research, Health Services and Delivery Research
