[361]
Lesson of the week Childhood leukaemia masquerading as juvenile ...
[94,3 KB]
From [bmj.bmjjournals.com] Last viewed: 07.09.2006
leukaemia
1185
NORTH LONDON CANCER NETWORK
LEUKAEMIA TUMOUR BOARD
Minutes of the meeting held on
21st January 2004
At
Committee Room 1, RFH
Chair: Stephen Mackinnon
Attendees
Heather McCulloch Clinical Research Nurse RFH
Jane Hudson Clinical Research Nurse UCLH
Lydia Ward Research Assistant UCLH
Sue Goddard Data Manager UCLH
Thurai Kumaran Consultant Haematologist N Mid
Susan Norris Pharmacist RFH
Denise Blake Pharmacist NLCN
Andres Virchis Consultant Haematologist Barnet/Ch
Kirit Ardeshna Consultant Ha...
[362]
leukaemia Choroidal infiltration in juvenile myelomonocytic
From [bjo.bmjjournals.com] Last viewed: 07.09.2006
leukaemia
Institute of Child Health & Great Ormond Street Hospital
Molecular Basis of Childhood Leukaemia
Thursday 23 – Friday 24 March 2006
Provisional Programme
Thursday 23 rd March 2006
Introduction
Hugh Brady, Institute of Child Health
The MLL Gene and Leukaemia
10.00 MLL fusion genes: what do they tell us about acute leukaemia ?
Eric So, Institute of Cancer Research, London
MLL fusions in leukaemia : different proteins, one function?
Robert Slany, University of Erlangen
11.20 T e a / c o f f e e
11.50 Pathological mechanisms in t(4;11) leukaemia : new insights and
perspectives
Rolf Marschalek, University of Frankfurt
12.30 MLL - Leukaemia and ...
[363]
Hypereosinophilic Syndrome in Acute Lymphoblastic Leukaemia
[19,6 KB]
From [taylorandfrancis.metapress.com] Last viewed: 07.09.2006
52
JCPSP 2005, Vol. 15 (1): 52-54
I
NTRODUCTION
Neoplasm noted at birth and during the 1st month of life are
strictly defined as congenital.
1
Acute leukaemia is rare in
infants. It is characterized by non-specific symptomatology
requiring high index of suspicion for referral and diagnosis
with peculiar biological features. Only few cases of congenital
leukaemia have been reported in literature and estimated
175-200 reports of congenital leukaemia have appeared in
literature.
2
Neonatal leukaemia occurs at the rate of 1 per 5
million births.
1
Furthermore, it is observed that 18% of all
children of acute non-lymphocytic leukaemia and 3% of all
children with acute lymphoblastic leukaemia are below 1 year
of age.
C
ASE REPORT
C
ASE
1: A 10 days old male baby was admitted with ...
[364]
Nephrotic Syndrome Associated with Chronic Lymphocytic Leukaemia
[19,0 KB]
From [taylorandfrancis.metapress.com] Last viewed: 07.09.2006
52
JCPSP 2005, Vol. 15 (1): 52-54
I
NTRODUCTION
Neoplasm noted at birth and during the 1st month of life are
strictly defined as congenital.
1
Acute leukaemia is rare in
infants. It is characterized by non-specific symptomatology
requiring high index of suspicion for referral and diagnosis
with peculiar biological features. Only few cases of congenital
leukaemia have been reported in literature and estimated
175-200 reports of congenital leukaemia have appeared in
literature.
2
Neonatal leukaemia occurs at the rate of 1 per 5
million births.
1
Furthermore, it is observed that 18% of all
children of acute non-lymphocytic leukaemia and 3% of all
children with acute lymphoblastic leukaemia are below 1 year
of age.
C
ASE REPORT
C
ASE
1: A 10 days old male baby was admitted with ...
[365]
Acute megakaryoblastic leukaemia in pregnancy presenting as ...
[19,9 KB]
From [taylorandfrancis.metapress.com] Last viewed: 07.09.2006
52
JCPSP 2005, Vol. 15 (1): 52-54
I
NTRODUCTION
Neoplasm noted at birth and during the 1st month of life are
strictly defined as congenital.
1
Acute leukaemia is rare in
infants. It is characterized by non-specific symptomatology
requiring high index of suspicion for referral and diagnosis
with peculiar biological features. Only few cases of congenital
leukaemia have been reported in literature and estimated
175-200 reports of congenital leukaemia have appeared in
literature.
2
Neonatal leukaemia occurs at the rate of 1 per 5
million births.
1
Furthermore, it is observed that 18% of all
children of acute non-lymphocytic leukaemia and 3% of all
children with acute lymphoblastic leukaemia are below 1 year
of age.
C
ASE REPORT
C
ASE
1: A 10 days old male baby was admitted with ...
[366]
Long-term Survival of Acute Leukaemia One Patient’s Story
[20,0 KB]
From [taylorandfrancis.metapress.com] Last viewed: 07.09.2006
52
JCPSP 2005, Vol. 15 (1): 52-54
I
NTRODUCTION
Neoplasm noted at birth and during the 1st month of life are
strictly defined as congenital.
1
Acute leukaemia is rare in
infants. It is characterized by non-specific symptomatology
requiring high index of suspicion for referral and diagnosis
with peculiar biological features. Only few cases of congenital
leukaemia have been reported in literature and estimated
175-200 reports of congenital leukaemia have appeared in
literature.
2
Neonatal leukaemia occurs at the rate of 1 per 5
million births.
1
Furthermore, it is observed that 18% of all
children of acute non-lymphocytic leukaemia and 3% of all
children with acute lymphoblastic leukaemia are below 1 year
of age.
C
ASE REPORT
C
ASE
1: A 10 days old male baby was admitted with ...
[367]
Torticollis revealing as a symptom of acute lymphoblastic ...
[20,5 KB]
From [taylorandfrancis.metapress.com] Last viewed: 07.09.2006
52
JCPSP 2005, Vol. 15 (1): 52-54
I
NTRODUCTION
Neoplasm noted at birth and during the 1st month of life are
strictly defined as congenital.
1
Acute leukaemia is rare in
infants. It is characterized by non-specific symptomatology
requiring high index of suspicion for referral and diagnosis
with peculiar biological features. Only few cases of congenital
leukaemia have been reported in literature and estimated
175-200 reports of congenital leukaemia have appeared in
literature.
2
Neonatal leukaemia occurs at the rate of 1 per 5
million births.
1
Furthermore, it is observed that 18% of all
children of acute non-lymphocytic leukaemia and 3% of all
children with acute lymphoblastic leukaemia are below 1 year
of age.
C
ASE REPORT
C
ASE
1: A 10 days old male baby was admitted with ...
[368]
Early Second Leukaemia in a Patient with Successfully Treated ...
[19,7 KB]
From [taylorandfrancis.metapress.com] Last viewed: 07.09.2006
52
JCPSP 2005, Vol. 15 (1): 52-54
I
NTRODUCTION
Neoplasm noted at birth and during the 1st month of life are
strictly defined as congenital.
1
Acute leukaemia is rare in
infants. It is characterized by non-specific symptomatology
requiring high index of suspicion for referral and diagnosis
with peculiar biological features. Only few cases of congenital
leukaemia have been reported in literature and estimated
175-200 reports of congenital leukaemia have appeared in
literature.
2
Neonatal leukaemia occurs at the rate of 1 per 5
million births.
1
Furthermore, it is observed that 18% of all
children of acute non-lymphocytic leukaemia and 3% of all
children with acute lymphoblastic leukaemia are below 1 year
of age.
C
ASE REPORT
C
ASE
1: A 10 days old male baby was admitted with ...
[369]
Vertebral compression fractures in acute lymphoblastic leukaemia ...
[124,2 KB]
From [adc.bmjjournals.com] Last viewed: 07.09.2006
Non-occupational exposure to pesticides and childhood acute leukaemia
Florence Menegaux and Jacqueline Clavel
INSERM U170-IFR69, 16 av. Paul Vaillant Couturier, 94800 Villejuif, France
Tel: 33 1 45 59 51 53 – Fax: 33 1 45 59 51 51 – E-mail: menegaux@vjf.inserm.fr
Summary
The present study, which included 280 cases of acute leukaemia and 288 controls,
investigated the relationship between childhood acute leukaemia (AL) and non-occupational
exposure to pesticide during pregnancy and childhood. Acute leukaemia was associated to
home insecticide use during pregnancy and during childhood (OR=1.8 [1.2-2.8], OR=1.7
[1.1-2.4], respectively) and garden insecticide use during childhood (OR=2.1 [1.1-4.0]). The
association was more pronounced when garden insecticide was used during both pregnancy
and childhood (OR=2.9 [1.1-7.3]). Lice infestation of the index child was also associated with
...
[370]
TITLE PAGE Article title Successful treatment of Juvenile ...
[112,1 KB]
From [www.bloodjournal.org] Last viewed: 07.09.2006
Non-occupational exposure to pesticides and childhood acute leukaemia
Florence Menegaux and Jacqueline Clavel
INSERM U170-IFR69, 16 av. Paul Vaillant Couturier, 94800 Villejuif, France
Tel: 33 1 45 59 51 53 – Fax: 33 1 45 59 51 51 – E-mail: menegaux@vjf.inserm.fr
Summary
The present study, which included 280 cases of acute leukaemia and 288 controls,
investigated the relationship between childhood acute leukaemia (AL) and non-occupational
exposure to pesticide during pregnancy and childhood. Acute leukaemia was associated to
home insecticide use during pregnancy and during childhood (OR=1.8 [1.2-2.8], OR=1.7
[1.1-2.4], respectively) and garden insecticide use during childhood (OR=2.1 [1.1-4.0]). The
association was more pronounced when garden insecticide was used during both pregnancy
and childhood (OR=2.9 [1.1-7.3]). Lice infestation of the index child was also associated with
...
[371]
Pseudohypoxaemia in a patient with acute leukaemia
[155,0 KB]
From [thorax.bmjjournals.com] Last viewed: 07.09.2006
Non-occupational exposure to pesticides and childhood acute leukaemia
Florence Menegaux and Jacqueline Clavel
INSERM U170-IFR69, 16 av. Paul Vaillant Couturier, 94800 Villejuif, France
Tel: 33 1 45 59 51 53 – Fax: 33 1 45 59 51 51 – E-mail: menegaux@vjf.inserm.fr
Summary
The present study, which included 280 cases of acute leukaemia and 288 controls,
investigated the relationship between childhood acute leukaemia (AL) and non-occupational
exposure to pesticide during pregnancy and childhood. Acute leukaemia was associated to
home insecticide use during pregnancy and during childhood (OR=1.8 [1.2-2.8], OR=1.7
[1.1-2.4], respectively) and garden insecticide use during childhood (OR=2.1 [1.1-4.0]). The
association was more pronounced when garden insecticide was used during both pregnancy
and childhood (OR=2.9 [1.1-7.3]). Lice infestation of the index child was also associated with
...
[372]
Chemotherapy and marrow transplantation for congenital leukaemia
[151,1 KB]
From [fn.bmjjournals.com] Last viewed: 07.09.2006
Non-occupational exposure to pesticides and childhood acute leukaemia
Florence Menegaux and Jacqueline Clavel
INSERM U170-IFR69, 16 av. Paul Vaillant Couturier, 94800 Villejuif, France
Tel: 33 1 45 59 51 53 – Fax: 33 1 45 59 51 51 – E-mail: menegaux@vjf.inserm.fr
Summary
The present study, which included 280 cases of acute leukaemia and 288 controls,
investigated the relationship between childhood acute leukaemia (AL) and non-occupational
exposure to pesticide during pregnancy and childhood. Acute leukaemia was associated to
home insecticide use during pregnancy and during childhood (OR=1.8 [1.2-2.8], OR=1.7
[1.1-2.4], respectively) and garden insecticide use during childhood (OR=2.1 [1.1-4.0]). The
association was more pronounced when garden insecticide was used during both pregnancy
and childhood (OR=2.9 [1.1-7.3]). Lice infestation of the index child was also associated with
...
[373]
DWIB Leukaemia Trust
From [www.dwib.org] Last viewed: 07.09.2006
For lack of knowledge our people are dying
Dear Sir/Madam
DWIB LEUKAEMIA TRUST
INVITATION TO BE A PATRON OF THE TRUST
The Dwib Leukaemia Trust (Ghana) has been formed with the aim to increase awareness
of leukaemia in the West African sub-Region and create access to effective diagnostic
and treatment resources. Most of all, it aims to set up the first bone marrow register in
West Africa, possibly at the Korle- bu Teaching Hospital.
We acknowledge with deep respect your singular achievements in your field of
endeavour and your interest in progress and development. It is in the light of this that we
feel honoured to invite you to become a patron of the organization. We believe that your
credibility and respect will greatly enhance the achievements of the Trust’s noble aims
and objectives.
We hope that should you accept, together, we shall convert the unpleasant tragedy of
leukaemia ...
[374]
23: Leukaemia (C91-C95)
From [www.qub.ac.uk] Last viewed: 07.09.2006
Cancer in Northern Ireland 1993 - 2001: A Comprehensive Report 129
23: Leukaemia (C91-C95)
Incidence
In 2001, leukaemia was the fourteenth most common cancer in males and sixteenth commonest
in females. On average 92 males and 65 females were diagnosed as having leukaemia each year,
accounting for about 2% of male and 1% of female cancers.
Age
Given the levels of disease in 2001, the risk of getting leukaemia before the age of 75 years was 1
in 161 for males and 1 in 361 for females (Table 23a). Fifty percent of males were diagnosed
under the age of 68 years, whilst for females it was 69 years. The average annual incidence of
leukaemia was highest in 70-74 year old males and females, with higher age-specific rates in
males than females (Figure 23a).
Prevalence
In Northern Ireland on 31st December 2001, there were 294 males and 208 females alive who
had leukaemia diagnosed between ...
[375]
15. Leukaemia
From [www.qub.ac.uk] Last viewed: 07.09.2006
Survival of Cancer Patients in Northern Ireland 1993-96
65
Incidence and Mortality
In 1996, leukaemia was the fifteenth most common cancer in men and sixteenth in women, accounting for almost 2%
of all cancers registered. Between 1993 and 1996, an average of 87 men and 61 women were registered annually as
having leukaemia , whilst approximately 49 men and 38 women died each year from this disease. There were no
statistically significant trends (P>0.05) in either the incidence or mortality EASRs exhibited by men or women (Figure
15.1).
Table 15.1: Summary table for adult leukaemia
Summary 1993-1996
Males
Females
Average annual number of leukaemia cases registered
87
61
Average annual number of leukaemia deaths
49
38
% cases excluded from survival analysis
4.1
3.7
Relative survival rates (Age-standardised rates) (%)
1-year
55 (61) ...
[376]
Fix and Perm- Leukaemia diagnostic
From [www.medipex.co.uk] Last viewed: 07.09.2006
Winter/Spring 2005 Issue 2
Overview
The invention is a diagnostic kit of reagents for fixing and
permeabilising cells which can be used in the field of
leukaemia .
It
is
especially
but
not
exclusively,
haematopoietic cells with improved retention of cellular
morphology and antigen visualisation in comparison to
currently available methods. It allows analysis of a broader
range of intracellular antigens, whilst improving retention of
morphological characteristics.
Problem
Current methods of fixation and permeabilisation destroy
cell’s surface proteins and compromise cellular morphology.
In an attempt to overcome this problem detergents have
been used to render the cellular membrane permeable
which themselves are potent entities in themselves, and
may also detrimentally affect cellular morphology.
A further problem may caused by ...
[377]
Acute leukaemia in children with Down syndrome: a population-based ...
From [www.nopho.org] Last viewed: 07.09.2006
Acute leukaemia in children with Down syndrome:
a population-based Nordic study
The increased incidence of leukaemia in individuals with
Down syndrome (DS) was observed nearly 50 years ago (Krivit
& Good, 1957). Since then, many reports have confirmed the
association and described the special features of the leukaemias
seen in DS children (Robison et al , 1984; Levitt et al , 1990;
Ravindranath et al , 1992; Zipursky et al , 1992; Slordahl et al ,
1993; Creutzig et al , 1996; Lie et al , 1996; Dördelmann et al ,
1998; Lange et al , 1998; Chessells et al , 2001; Hasle, 2001;
Goldacre et al , 2004). The relative risk of acute leukaemia in
the first 5 years of life is 56 times that of non-DS individuals
(Hasle et al , 2000), and acute myeloid leukaemia (AML) is
equally frequent as acute lymphoid leukaemia (ALL) (Lange,
2000). AML in DS children is characterized by unique features. ...
[378]
CHRONIC LYMPHOID LEUKAEMIA (ICD-IX 204.1)
From [www.registri-tumori.it] Last viewed: 07.09.2006
AGE
CLASSES
Men
Women
15-44
2
0
45-54
8
4
55-64
23
11
65-74
21
19
75+
21
29
ALL
75
63
obs
rel
obs
rel
obs
rel
1 year
92
96
86
89
89
93
3 years
78
88
75
84
77
86
5 years
59
73
63
77
61
75
95% CI
(48-70)
(59-86)
(51-74)
(62-90)
(53-69)
(65-84)
AGE
CLASSES
Men
Women
15-44
1
1
45-54
5
7
55-64
27
15
65-74
27
22
75+
34
18
ALL
94
63
obs
rel
obs
rel
obs
rel
1 year
87
91
81
83
85
88 ...
[379]
LEUKAEMIA (ICD-IX 204-208)
From [www.registri-tumori.it] Last viewed: 07.09.2006
AGE
CLASSES
Men
Women
15-44
36
27
45-54
25
26
55-64
61
40
65-74
59
55
75+
57
80
ALL
238
228
obs
rel
obs
rel
obs
rel
1 year
57
59
54
56
56
57
3 years
42
46
36
39
39
43
5 years
32
38
29
33
30
36
95% CI
(26-38)
(32-46)
(23-35)
(27-41)
(26-35)
(31-41)
AGE
CLASSES
Men
Women
15-44
22
14
45-54
12
18
55-64
45
31
65-74
56
48
75+
70
62
ALL
205
173
obs
rel
obs
rel
obs
rel
1 year
64
67
51
52
...
[380]
MYELOID LEUKAEMIA (ICD-IX 205)
From [www.registri-tumori.it] Last viewed: 07.09.2006
[381]
Molecular detectionof minimal residual diseasefor patients with ...
From [sunzi1.lib.hku.hk] Last viewed: 07.09.2006
[382]
Treatment of Childhood Acute Lymphoblastic Leukaemia— The Local ...
From [sunzi1.lib.hku.hk] Last viewed: 07.09.2006
[383]
CONGENITAL LEUKAEMIA
From [www.cpsp.edu.pk] Last viewed: 07.09.2006
[384]
SLEUTHING THE CAUSES OF CHILDHOOD LEUKAEMIA
[151,8 KB]
From [www.icr.ac.uk] Last viewed: 10.07.2006
[385]
Role of the Paediatric Leukaemia Nurse Specialist
[569,3 KB]
From [www.cardiff.ac.uk] Last viewed: 06.07.2006
Web Immagini Gruppi Directory News altro »
Ricerca avanzata Preferenze
Cerca nel Web Cerca solo le pagine in Inglese Spiacenti, nessun contenuto associato a questo URL
Web
La ricerca di - cache:IwosmbcVgZIJ:www.cardiff.ac.uk/nursing/about/directorates/children/newsandevents/Julia%20Bailey%20Role%20of%20the%20Paediatric%20Leukaemia%20Nurse%20Specialist.ppt leukaemia filetype:pdf OR filetype:doc OR filetype:ppt OR filetype:xls OR filetype:rtf - non ha prodotto risultati in nessun documento. Suggerimenti:
Assicurarsi che tutte le parole siano state digitate correttamente.
Provare con parole chiave ...
[386]
DEPARTMENT OF CLINICAL HAEMATOLOGY SENIOR CLINICAL SCIENTIST ...
[79,3 KB]
From [www.eshg.org] Last viewed: 06.07.2006
DEPARTMENT OF CLINICAL HAEMATOLOGY
SENIOR CLINICAL SCIENTIST
Leukaemia Cytogenetics
Grade B (17-22 depending on experience)
£32,537 - £39,582 p.a. ? Full-time
An opportunity has arisen for an experienced Cytogeneticist to join the Haemato-
Oncology team within this friendly and progressive department. Applications are
invited from highly motivated individuals with experience in haematology to work in
the challenging and interesting field of haematological malignancy. The successful
applicant will lead the section and take day-to-day responsibility for cytogenetic
analysis on a wide range of paediatric and adult haematological malignancies.
The cytogenetics section is integrated with phenotyping and molecular genetics and
provides the Haemato-Oncology Diagnostic Service to the Eastern Region. It has close
links with the University of Cambridge Haematology Department (Professor Tony
Green) through ...
[387]
MRC Acute Lymphoblastic Leukaemia Trial XII
[73,7 KB]
From [www.ctsu.ox.ac.uk] Last viewed: 06.07.2006
leukaemia
1185
(To be on headed paper)
Medical Research Council Acute Lymphoblastic Leukaemia Trial XII
Version 4.0 May 2005
Parent / Guardian Information Sheet
Your child is being invited to take part in a research study. Before you and your child decide it is important for you both to understand why the research is being done and what it will involve. Please take time to read the following information carefully and discuss it with others if you wish. Ask us if there is anything that is not clear or if you would like more information. Take time to decide whether or not you wish your child to take part.
Thank you for reading this.
What is the purpose of the study?
The purpose of this study is to find out more about how best to treat patients with Acute Lymphoblastic Leukaemia (ALL). The more people who take part in these studies, the better the information ...
[388]
RESULTS BROMSGROVE LEUKAEMIA 5K FUN RUN 2006
[14,1 KB]
From [www.lrfbromsgrove.org.uk] Last viewed: 06.07.2006
RESULTS
1
0:21:37 RICHARDSON, Ben
Bromsgrove & Redditch AC
JunM
509
1
2
0:21:38 BYNG, James
Unattached
SenM
536
2
3
0:21:50 DAVIS, Antony
Unattached
M35+
553
3
4
0:23:35 JOHNSON, Craig
Worcester AC
JunM
544
4
5
0:24:46 BYNG, Nicholas
Tri-Team/BTA
SenM
537
5
6
0:24:51 WOODWISS, Lauren
Unattached
JunW
810
6
7
0:25:00 RICHARDSON, Philip
Bromsgrove & Redditch AC
M35+
510
7
8
0:25:44 HARVEY, Paul
Unattached
SenM
549
8
9
0:26:10 WATSON, Jake
Unattached
JunM
517
9
10
0:26:11 PHILLIPS, John
Unattached
M35+
518
10
11
0:26:48 WARD, Lucy
Unattached
SenW
885
11
12
0:27:00 JARNIS, Gary
Unattached
SenM
524
12
13
...
[389]
RESULTS BROMSGROVE LEUKAEMIA 10K FUN RUN 2006
[20,5 KB]
From [www.lrfbromsgrove.org.uk] Last viewed: 06.07.2006
RESULTS
1
0:33:07 MALIN, Richard
Bromsgrove & Redditch AC
M35+
175
1
2
0:35:59 LEWIS, Mark
Royal Navy AC
M35+
99
2
3
0:36:17 KEYTE, Ian
Bromsgrove & Redditch AC
M35+
125
3
4
0:36:33 OLINS, Paul
Bromsgrove & Redditch AC
M35+
137
4
5
0:36:36 MCGILL, Trevor
Droitwich AC
M35+
101
5
6
0:36:42 DANDO, Richard
Unattached
SenM
169
6
7
0:37:03 DAVIES, Paul
Centurion RC
M35+
78
7
8
0:37:14 BURKE, Kevin
Stourbridge RC
M35+
102
8
9
0:37:19 PENN, Chris
Unattached
SenM
39
9
10
0:38:16 JENKINS, Huw
Bromsgrove & Redditch AC
M35+
29
10
11
0:38:29 GRAHAM, Mark
Bromsgrove & Redditch AC
M35+
106
11
12
0:38:48 ATKINS, Paul
Bromsgrove ...
[390]
Editorial Childhood Lymphoma and Leukaemia
[108,2 KB]
From [www.jpma.org.pk] Last viewed: 06.07.2006
Pakistan falls into a low risk region for Non-
Hodgkins Lymphoma (NHL) in males and females, graded
1 on a scale of 1-5. Males and females fall into a moderate
risk region for leukaemia , graded 2 for males and 3 for
females on the same scale (Figure 1).
1
These estimates are
based on the data of Karachi South published in the Cancer
Incidence in the Five Continents.
2
Karachi South (KS) is the southern-most district of
Karachi with a population of 1,724,915; 929,394 (54%)
males and 795,521 (46%) females; annual growth rate of
1.94% as calculated by the Federal Census Bureau.
3
The
population distribution of KS is similar to the population
distribution of Pakistan as regards age, gender, and religion.
KS has the distinction of being the only district in the coun-
try with a representation of all ethnic and socio-economic
groups of the country. It thus ...