17 research outputs found
The Amalgamated Society of Engineers, 1880-1914 : a study of trade union government, politics, and industrial policy
In 1880 the Amalgamated Society
of
Engineers
(ASE)
consisted of
largely autonomous
local trade
societies seeking unilaterally
to
regulate
the terns
and conditions under which engineering craftsmen were employed.
The Executive Council
(which
spent most of
its time
administering
the
system
of centralised
benefits)
consisted of part-time members
drawn from,
and
elected
by, the London
members.
In 1892 the first full-time Executive Council
was elected as part of a general reform of
the Society's
government;
the
reforms
did
not change
the A. S. E. 's
craft character rather
they
were
designed
to improve the
execution of
traditional
policies.
As the
climax of a
long
campaign
for the
eight-hour
day the Executive
Council
called a strike of
its London
members
in 1897. The
ensuing
dispute,
which
the Employers
extended to
all
districts, lasted thirty
weeks, and was
ended on
the terms laid down by the
recently
formed Engineering Employers'
Federation
(EEF).
Under the terms
of settlement
the A. S. E.
accepted a
procedure
for
avoiding
disputes
and
Management's
right to
prerogative over
matters Which previously
it had
claimed unilateral control.
The Society
disaffiliated from the T. U. C. because
of
the Parliamentary Committee's failure
to tobilize trade union support for the
engineers eight-hour struggle.
Affiliation
was made
to the General Federation
of
Trade Unions
(GFTU)
in the
false hope that this Federation
would augment
the A. S. E. 'a industrial
strength.
It is convenient to discuss the A. S. E. 's
reaction to the 1897-98
defeat and its consequences under
headings
which indicate the
main
themes.
Technical change
From the
mid-1880's something approaching a revolution occurred
in
machine
technology based
upon
improved high
speed steels.
The
establishment
of
the EEF
and
the sustained attack upon craft methods of production can
be
largely explained
by the
employers'
determination to fully
exploit
the
new
technology.
Government
Constitutional
authority within
the A. S. E.
was
divided between
the Executive Council,
a
lay Delegate Meeting,
and a
lay Final Appeal Court.
There
was no policy making
body. The Society
was governed according
to the
rule
book
which was unaffected
by the terms
under which
the 1697-98 dispute
was settled.
Consequently it
was
difficult for the Executive Council to
develop
collective
bargaining
and
to
restrain
district
committees,
from
acting
in breach of the agreement,
but
within
the
rules of
the Society. Both the
Delegate Meeting
and
the Final Appeal Court tended to defend local
as against
central
decision
making authority.
The Executive Council's
action
in 1903,
withdrawing
benefit from
members of
the Clyde
striking against a wages reduction,
led to
a serious weakening
in their
authority.
Three Executive Councilmen
were
defeated
when seeking re-election,
the Final Appeal Court
partially over-ruled
the Executive's benefit decision,
and
the 1904 Delegate Meeting limited the
Council's
right
to intervene in district
matters.
In 1912
after a complicated
dispute the Delegate Meeting dismissed the Executive Council from
office.
This
assertion of authority
by a rank and
file body
was not overtly influenced by
syndicalist ow
industrial
unionist
ideas.
Industrial Policy
The Executive Ceuneil intermittently
and uncertainly
tried to develep
collective
bargaining to
replace
lest
unilateral regulation while powerful
district
committees attempted
to
retain
their
previous methods of operation.
In 1902 the Executive
concluded
the Carlisle
agreement
for
controlling
the
introduction
of
the
premium
bonus. This
proved
to be
an unpopular agreement
and probably
discredited
collective
bargaining. The Executive
elected
in
1913, to
replace
the
one
dismissed by the 1912 Delegate Meeting,
after a
ballot
vote of members, ended
the Carlisle Agreement
and
the
general
agreement with
the EEF. Eventually the York
memorandum was approved
by the
members, which although
it incorporated
provisions which speeded up
the
procedure
for
avoiding disputes,
continued
those
aspects which
to
many
ASE
members, were
the humiliating terms
under which
the Society had been defeated.
After 1898
with
the Society formally
precluded
from
negotiations on management
matters an
informal
system of work place,
industrial
relations
began to
develop based
upon
district
committees and
the
widespread appointment of shop
stewards.
Polities
During these years the A. S. E. became involved in
politics
for the
first time. All ballets
on political questions were very small.
The A. S. E.
affiliated
to the Labour Party but
neither
the Independent Labour Party
(ILP)
nor
the Social Democratic Federation (SDF)
were active within the Society.
George Barnes
(General Secretary 1896-1908)
was an
influential
supporter of
the Socialist trade
union alliance upon which
the Labour Party
was established.
In 1914 the A. S. E.
members voted against raising a political
levy
under
the
1913 trade
union act.
From the turn
of
the
century most officials and active
members supported
the Labour Party
and
it
was sometimes argued
that the Society's
problems
(which
were
industrial)
could
be
solved
by
political action.
How,
was
never clear.
The developing sympathy among A. S. E. members for
a view of trade
union democracy which favoured
control exercised through district or workshop
organisation casts some light
on the development
of the shop stewards movement
during the War
Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation
NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family
Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in children in Sierra Leone: a randomised, double-blind, controlled trial
Background—Children account for a substantial proportion of cases and deaths from Ebola virus disease. We aimed to assess the safety and immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vectorbased vaccine, encoding glycoproteins from the Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in a paediatric population in Sierra Leone.
Methods—This randomised, double-blind, controlled trial was done at three clinics in Kambia district, Sierra Leone. Healthy children and adolescents aged 1–17 years were enrolled in three age cohorts (12–17 years, 4–11 years, and 1–3 years) and randomly assigned (3:1), via computer-generated block randomisation (block size of eight), to receive an intramuscular injection of either Ad26.ZEBOV (5 × 1010 viral particles; first dose) followed by MVA-BN-Filo (1 × 108 infectious units; second dose) on day 57 (Ebola vaccine group), or a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo (second dose) on day 57 (control group). Study team personnel (except for those with primary responsibility for study vaccine preparation), participants, and their parents or guardians were masked to study vaccine allocation. The primary outcome was safety, measured as the occurrence of solicited local and systemic adverse symptoms during 7 days after each vaccination, unsolicited systemic adverse events during 28 days after each vaccination, abnormal laboratory results during the study period, and serious adverse events or immediate reportable events throughout the study period. The secondary outcome was immunogenicity (humoral immune response), measured as the concentration of Ebola virus glycoprotein-specific binding antibodies at 21 days after the second dose. The primary outcome was assessed in all participants who had received at least one dose of study vaccine and had available reactogenicity data, and immunogenicity was assessed in all participants who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response. This study is registered at ClinicalTrials.gov, NCT02509494.
Findings—From April 4, 2017, to July 5, 2018, 576 eligible children or adolescents (192 in each of the three age cohorts) were enrolled and randomly assigned. The most common solicited local adverse event during the 7 days after the first and second dose was injection-site pain in all age groups, with frequencies ranging from 0% (none of 48) of children aged 1–3 years after placebo injection to 21% (30 of 144) of children aged 4–11 years after Ad26.ZEBOV vaccination. The most frequently observed solicited systemic adverse event during the 7 days was headache in the 12–17 years and 4–11 years age cohorts after the first and second dose, and pyrexia in the 1–3 years age cohort after the first and second dose. The most frequent unsolicited adverse event after the first and second dose vaccinations was malaria in all age cohorts, irrespective of the vaccine types. Following vaccination with MenACWY, severe thrombocytopaenia was observed in one participant aged 3 years. No other clinically significant laboratory abnormalities were observed in other study participants, and no serious adverse events related to the Ebola vaccine regimen were reported. There were no treatment-related deaths. Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second dose of the Ebola virus vaccine regimen were observed in 131 (98%) of 134 children aged 12–17 years (9929 ELISA units [EU]/mL [95% CI 8172–12 064]), in 119 (99%) of 120 aged 4–11 years (10 212 EU/mL [8419–12 388]), and in 118 (98%) of 121 aged 1–3 years (22 568 EU/mL [18 426–27 642]).
Interpretation—The Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen was well tolerated with no safety concerns in children aged 1–17 years, and induced robust humoral immune responses, suggesting suitability of this regimen for Ebola virus disease prophylaxis in children
Targeting the MAPK7/MMP9 axis for metastasis in primary bone cancer
Metastasis is the leading cause of cancer related death. This multistage process involves contribution from both tumour cells and the tumour stroma to release metastatic cells into the circulation. Circulating tumour cells (CTCs) survive circulatory cytotoxicity, extravasate and colonise secondary sites effecting metastatic outcome. Reprogramming the transcriptomic landscape is a metastatic hallmark but detecting underlying master regulators that drive pathological gene expression is a key challenge, especially in childhood cancer. Here we used whole tumour plus single cell RNA sequencing in primary bone cancer and CTCs to perform weighted gene co-expression network analysis to systematically detect coordinated changes in metastatic transcript expression. This approach with comparisons applied to data collected from cell line models, clinical samples and xenograft mouse models revealed MAPK7/MMP9 signalling as a driver for primary bone cancer metastasis. RNAi knockdown of MAPK7 reduces proliferation, colony formation, migration, tumour growth, macrophage residency/polarisation and lung metastasis. Parallel to these observations were reduction of activated interleukins IL1B, IL6, IL8 plus mesenchymal markers VIM and VEGF in response to MAPK7 loss. Our results implicate a newly discovered, multidimensional MAPK7/MMP9 signalling hub in primary bone cancer metastasis that is clinically actionable
Safety and long-term immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in adults in Sierra Leone: a combined open-label, non-randomised stage 1, and a randomised, double-blind, controlled stage 2 trial
Background
The Ebola epidemics in west Africa and the Democratic Republic of the Congo highlight an urgent need for safe and effective vaccines to prevent Ebola virus disease. We aimed to assess the safety and long-term immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vector-based vaccine, encoding glycoproteins from Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in Sierra Leone, a country previously affected by Ebola.
Methods
The trial comprised two stages: an open-label, non-randomised stage 1, and a randomised, double-blind, controlled stage 2. The study was done at three clinics in Kambia district, Sierra Leone. In stage 1, healthy adults (aged ≥18 years) residing in or near Kambia district, received an intramuscular injection of Ad26.ZEBOV (5×1010 viral particles) on day 1 (first dose) followed by an intramuscular injection of MVA-BN-Filo (1×108 infectious units) on day 57 (second dose). An Ad26.ZEBOV booster vaccination was offered at 2 years after the first dose to stage 1 participants. The eligibility criteria for adult participants in stage 2 were consistent with stage 1 eligibility criteria. Stage 2 participants were randomly assigned (3:1), by computer-generated block randomisation (block size of eight) via an interactive web-response system, to receive either the Ebola vaccine regimen (Ad26.ZEBOV followed by MVA-BN-Filo) or an intramuscular injection of a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo on day 57 (second dose; control group). Study team personnel, except those with primary responsibility for study vaccine preparation, and participants were masked to study vaccine allocation. The primary outcome was the safety of the Ad26.ZEBOV and MVA-BN-Filo vaccine regimen, which was assessed in all participants who had received at least one dose of study vaccine. Safety was assessed as solicited local and systemic adverse events occurring in the first 7 days after each vaccination, unsolicited adverse events occurring in the first 28 days after each vaccination, and serious adverse events or immediate reportable events occurring up to each participant’s last study visit. Secondary outcomes were to assess Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second vaccine in a per-protocol set of participants (ie, those who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response) and to assess the safety and tolerability of the Ad26.ZEBOV booster vaccination in stage 1 participants who had received the booster dose. This study is registered at ClinicalTrials.gov, NCT02509494.
Findings
Between Sept 30, 2015, and Oct 19, 2016, 443 participants (43 in stage 1 and 400 in stage 2) were enrolled; 341 participants assigned to receive the Ad26.ZEBOV and MVA-BN-Filo regimen and 102 participants assigned to receive the MenACWY and placebo regimen received at least one dose of study vaccine. Both regimens were well tolerated with no safety concerns. In stage 1, solicited local adverse events (mostly mild or moderate injection-site pain) were reported in 12 (28%) of 43 participants after Ad26.ZEBOV vaccination and in six (14%) participants after MVA-BN-Filo vaccination. In stage 2, solicited local adverse events were reported in 51 (17%) of 298 participants after Ad26.ZEBOV vaccination, in 58 (24%) of 246 after MVA-BN-Filo vaccination, in 17 (17%) of 102 after MenACWY vaccination, and in eight (9%) of 86 after placebo injection. In stage 1, solicited systemic adverse events were reported in 18 (42%) of 43 participants after Ad26.ZEBOV vaccination and in 17 (40%) after MVA-BN-Filo vaccination. In stage 2, solicited systemic adverse events were reported in 161 (54%) of 298 participants after Ad26.ZEBOV vaccination, in 107 (43%) of 246 after MVA-BN-Filo vaccination, in 51 (50%) of 102 after MenACWY vaccination, and in 39 (45%) of 86 after placebo injection. Solicited systemic adverse events in both stage 1 and 2 participants included mostly mild or moderate headache, myalgia, fatigue, and arthralgia. The most frequent unsolicited adverse event after the first dose was headache in stage 1 and malaria in stage 2. Malaria was the most frequent unsolicited adverse event after the second dose in both stage 1 and 2. No serious adverse event was considered related to the study vaccine, and no immediate reportable events were observed. In stage 1, the safety profile after the booster vaccination was not notably different to that observed after the first dose. Vaccine-induced humoral immune responses were observed in 41 (98%) of 42 stage 1 participants (geometric mean binding antibody concentration 4784 ELISA units [EU]/mL [95% CI 3736–6125]) and in 176 (98%) of 179 stage 2 participants (3810 EU/mL [3312–4383]) at 21 days after the second vaccination.
Interpretation
The Ad26.ZEBOV and MVA-BN-Filo vaccine regimen was well tolerated and immunogenic, with persistent humoral immune responses. These data support the use of this vaccine regimen for Ebola virus disease prophylaxis in adults