3,201 research outputs found
Fibroblast growth factor family as a potential target in the treatment of hepatocellular carcinoma.
Hepatocellular cancer (HCC) is currently the third leading cause of cancer death worldwide. The prognosis of patients diagnosed with late-stage disease is dismal due to high resistance to conventional systemic therapies. The introduction of sorafenib, despite its limited efficacy, as the standard systemic therapy for advanced HCC has paved a way for targeted molecular therapies for HCC. Fibroblast growth factor (FGF) signaling plays an important role in the developing embryo and the adult. The FGF signaling pathway is often hijacked by cancer cells, including HCC. Several alterations in FGF signaling correlate with poor outcome in HCC patients, suggesting that this family of signaling molecules plays an important role in the development of HCC. Multikinase inhibitors targeting FGF signaling are currently under investigation in clinical trials. This review discusses the current understanding of the biological and clinical implications of aberrant FGF signaling in the prognosis, diagnosis, and treatment of HCC
Follow-up practices for high-grade extremity Osteosarcoma
BACKGROUND: The optimal conduct of follow-up (FU) of patients with osteosarcoma is uncertain. In the absence of any formal validation of optimal timing and method of surveillance, guidance is provided by oncology societies' recommendations. FU is designed to detect either local recurrence or metastatic disease at a time when early treatment is still possible and might be effective. METHODS: We performed a retrospective analysis of 101 patients with high-grade extremity osteosarcoma in a single centre. Chest x-ray (CXR) was used as routine surveillance method; however patients with initial lung metastases or previous suspicious findings had computed tomography (CT) scans. RESULTS: With a median FU time of 30.7 months 34 patients relapsed. Relapse-free survival after 5 years was 61% (CI 52%; 73%), late relapses occurred in only two patients between 2 and 5 years of FU. Twenty-five of the 34 relapses were detected at routine FU appointments. All 8 local recurrences were noted clinically. Twenty-two patients had metastases confined to the lungs, either detected on CXR or CT. Thirty-two percent of patients with lung metastases only were salvaged successfully. CONCLUSIONS: Routine FU in high-grade osteosarcoma results in clinical detection of local relapse, and detection of lung metastases by CXR at a time when metastatectomy is possible. The optimal time interval for FU appointments is not known, however we recommend more frequent surveillance visits during the two years after treatment. We hypothesize that routine CT scans are not required and propose CXR for detection of lung metastases
Vacuum Stability of the wrong sign Scalar Field Theory
We apply the effective potential method to study the vacuum stability of the
bounded from above (unstable) quantum field potential. The
stability ( and the mass renormalization
( conditions force the effective
potential of this theory to be bounded from below (stable). Since bounded from
below potentials are always associated with localized wave functions, the
algorithm we use replaces the boundary condition applied to the wave functions
in the complex contour method by two stability conditions on the effective
potential obtained. To test the validity of our calculations, we show that our
variational predictions can reproduce exactly the results in the literature for
the -symmetric theory. We then extend the applications
of the algorithm to the unstudied stability problem of the bounded from above
scalar field theory where classical analysis prohibits the
existence of a stable spectrum. Concerning this, we calculated the effective
potential up to first order in the couplings in space-time dimensions. We
find that a Hermitian effective theory is instable while a non-Hermitian but
-symmetric effective theory characterized by a pure imaginary
vacuum condensate is stable (bounded from below) which is against the classical
predictions of the instability of the theory. We assert that the work presented
here represents the first calculations that advocates the stability of the
scalar potential.Comment: 21pages, 12 figures. In this version, we updated the text and added
some figure
The epigenetic impacts of social stress: how does social adversity become biologically embedded?
Epigenetic mechanisms are implicated in the processes through which social stressors erode health in humans and other animals. Here I review progress in elucidating the biological pathways underlying the social gradient in health, with particular emphasis on how behavioral stresses influence epigenomic variation linked to health. The evidence that epigenetic changes are involved in embedding of social status-linked chronic stress is reviewed in the context of current knowledge about behavior within animal dominance hierarchies and the impacts of social position on behaviors that affect health. The roles of epigenetic mechanisms in responses to trauma and the evidence for their involvement in intergenerational transmission of the biological impacts of traumatic stress are also considered. Taken together, the emerging insights have important implications for development of strategies to improve societal health and well-being
Composite Leptoquarks at the LHC
If electroweak symmetry breaking arises via strongly-coupled physics, the
observed suppression of flavour-changing processes suggests that fermion masses
should arise via mixing of elementary fermions with composite fermions of the
strong sector. The strong sector then carries colour charge, and may contain
composite leptoquark states, arising either as TeV scale resonances, or even as
light, pseudo-Nambu-Goldstone bosons. The latter, since they are coupled to
colour, get a mass of the order of several hundred GeV, beyond the reach of
current searches at the Tevatron. The same generic mechanism that suppresses
flavour-changing processes suppresses leptoquark-mediated rare processes,
making it conceivable that the many stringent constraints may be evaded. The
leptoquarks couple predominantly to third-generation quarks and leptons, and
the prospects for discovery at LHC appear to be good. As an illustration, a
model based on the Pati-Salam symmetry is described, and its embedding in
models with a larger symmetry incorporating unification of gauge couplings,
which provide additional motivation for leptoquark states at or below the TeV
scale, is discussed.Comment: 10 pp, version to appear in JHE
Borrelia recurrentis employs a novel multifunctional surface protein with anti-complement, anti-opsonic and invasive potential to escape innate immunity
Borrelia recurrentis, the etiologic agent of louse-borne relapsing fever in humans, has evolved strategies, including antigenic variation, to evade immune defence, thereby causing severe diseases with high mortality rates. Here we identify for the first time a multifunctional surface lipoprotein of B. recurrentis, termed HcpA, and demonstrate that it binds human complement regulators, Factor H, CFHR-1, and simultaneously, the host protease plasminogen. Cell surface bound factor H was found to retain its activity and to confer resistance to complement attack. Moreover, ectopic expression of HcpA in a B. burgdorferi B313 strain, deficient in Factor H binding proteins, protected the transformed spirochetes from complement-mediated killing. Furthermore, HcpA-bound plasminogen/plasmin endows B. recurrentis with the potential to resist opsonization and to degrade extracellular matrix components. Together, the present study underscores the high virulence potential of B. recurrentis. The elucidation of the molecular basis underlying the versatile strategies of B. recurrentis to escape innate immunity and to persist in human tissues, including the brain, may help to understand the pathological processes underlying louse-borne relapsing fever
A telephone survey of cancer awareness among frontline staff: informing training needs
Background:
Studies have shown limited awareness about cancer risk factors among hospital-based staff. Less is known about general cancer awareness among community frontline National Health Service and social care staff.
Methods:
A cross-sectional computer-assisted telephone survey of 4664 frontline community-based health and social care staff in North West England.
Results:
A total of 671 out of 4664 (14.4%) potentially eligible subjects agreed to take part. Over 92% of staff recognised most warning signs, except an unexplained pain (88.8%, n=596), cough or hoarseness (86.9%, n=583) and a sore that does not heal (77.3%, n=519). The bowel cancer-screening programme was recognised by 61.8% (n=415) of staff. Most staff agreed that smoking and passive smoking ‘increased the chance of getting cancer.’ Fewer agreed about getting sunburnt more than once as a child (78.0%, n=523), being overweight (73.5%, n=493), drinking more than one unit of alcohol per day (50.2%, n=337) or doing less than 30 min of moderate physical exercise five times a week (41.1%, n=276).
Conclusion:
Cancer awareness is generally good among frontline staff, but important gaps exist, which might be improved by targeted education and training and through developing clearer messages about cancer risk factors
5D UED: Flat and Flavorless
5D UED is not automatically minimally flavor violating. This is due to flavor
asymmetric counter-terms required on the branes. Additionally, there are likely
to be higher dimensional operators which directly contribute to flavor
observables. We document a mostly unsuccessful attempt at utilizing
localization in a flat extra dimension to resolve these flavor constraints
while maintaining KK-parity as a good quantum number. It is unsuccessful
insofar as we seem to be forced to add brane operators in such a way as to
precisely mimic the effects of a double throat warped extra dimension. In the
course of our efforts, we encounter and present solutions to a problem common
to many extra dimensional models in which fields are "doubly localized:"
ultra-light modes. Under scrutiny, this issue seems tied to an intrinsic
tension between maintaining Kaluza-Klein parity and resolving mass hierarchies
via localization.Comment: 27 pages, 6 figure
Vertical Field Effect Transistor based on Graphene-WS2 Heterostructures for flexible and transparent electronics
The celebrated electronic properties of graphene have opened way for
materials just one-atom-thick to be used in the post-silicon electronic era. An
important milestone was the creation of heterostructures based on graphene and
other two-dimensional (2D) crystals, which can be assembled in 3D stacks with
atomic layer precision. These layered structures have already led to a range of
fascinating physical phenomena, and also have been used in demonstrating a
prototype field effect tunnelling transistor - a candidate for post-CMOS
technology. The range of possible materials which could be incorporated into
such stacks is very large. Indeed, there are many other materials where layers
are linked by weak van der Waals forces, which can be exfoliated and combined
together to create novel highly-tailored heterostructures. Here we describe a
new generation of field effect vertical tunnelling transistors where 2D
tungsten disulphide serves as an atomically thin barrier between two layers of
either mechanically exfoliated or CVD-grown graphene. Our devices have
unprecedented current modulation exceeding one million at room temperature and
can also operate on transparent and flexible substrates
Unintended Consequences of Incentive Provision for Behaviour Change and Maintenance around Childbirth
Financial (positive or negative) and non-financial incentives or rewards are increasingly used in attempts to influence health behaviours. While unintended consequences of incentive provision are discussed in the literature, evidence syntheses did not identify any primary research with the aim of investigating unintended consequences of incentive interventions for lifestyle behaviour change. Our objective was to investigate perceived positive and negative unintended consequences of incentive provision for a shortlist of seven promising incentive strategies for smoking cessation in pregnancy and breastfeeding. A multi-disciplinary, mixed-methods approach included involving two service-user mother and baby groups from disadvantaged areas with experience of the target behaviours as study co-investigators. Systematic reviews informed the shortlist of incentive strategies. Qualitative semi-structured interviews and a web-based survey of health professionals asked open questions on positive and negative consequences of incentives. The participants from three UK regions were a diverse sample with and without direct experience of incentive interventions: 88 pregnant women/recent mothers/partners/family members; 53 service providers; 24 experts/decision makers and interactive discussions with 63 conference attendees. Maternity and early years health professionals (n = 497) including doctors, midwives, health visitors, public health and related staff participated in the survey. Qualitative analysis identified ethical, political, cultural, social and psychological implications of incentive delivery at population and individual levels. Four key themes emerged: how incentives can address or create inequalities; enhance or diminish intrinsic motivation and wellbeing; have a positive or negative effect on relationships with others within personal networks or health providers; and can impact on health systems and resources by raising awareness and directing service delivery, but may be detrimental to other health care areas. Financial incentives are controversial and generated emotive and oppositional responses. The planning, design and delivery of future incentive interventions should evaluate unexpected consequences to inform the evidence for effectiveness, cost-effectiveness and future implementation
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