Recursion and Ambiguity: a Linguistic and Computational Perspective

In this chapter I will be concerned with what characterizes human language and the parser that computes it in real communicative situations. I will start by discussing and dismissing Hauser, Chomsky and Fitch's(2002) (HC&F) disputed claim that the "only uniquely human component of the faculty of language" be "recursion". I will substantiate my rejection of HC&F's claims, with the fact that recursion only appears in mature and literate language - an opinion also shared by some papers in a book on recursion by Harry van der Hulst (2010). I will then present in detail Chomsky's proposal - now part of the Minimalist Theory (MT) - of the architecture of the human parser as being based on Phases. I will accept this part of the theory and compare it with the computational architecture contained in a system for deep text understanding called Getaruns (Delmonte,2007;2009). I will then argue in favour of what I regard the peculiar component of human language faculty that is "the ability to associate meaning to deficient propositions and generic linguistic expressions, which are highly ambiguous in their structure”. And this is also due to the presence of recursion (but not only). I will then speak in favour of a parser that takes "context" into account and strives for a "complete" syntactic representation. As to the problem of ambiguity, I will introduce the use of a computational device, a lookahead mechanism, which is presented in association with the need to specify UG parameters characterizing a given language. I will discuss the use of psychologically viable Parsing Strategies implemented in the parser to overcome ambiguity and prevent Garden Path, whenever possible. This will be highlighted by reference to peculiar features associated to different languages, Italian and English. Eventually, I will present a theory that encompasses all my previous proposals and is called LSLT

Recent trends in cutaneous malignant melanoma in the Yorkshire region of England; incidence, mortality and survival in relation to stage of disease, 1993–2003

The aim of this study was to investigate recent trends in incidence, mortality and survival in patients diagnosed with malignant melanoma (MM) in relation to stage (Breslow thickness). Cases of primary invasive and in situ MM diagnosed between 1st January 1993 and 31st December 2003 in the former Yorkshire Health Authority were identified from cancer registry data. Over the study period, the incidence of invasive MM increased from 5.4 to 9.7 per 100 000 in male subjects and from 7.5 to 13.1 per 100 000 in female subjects. Most of this increase was seen in thin tumours (<1.5 mm). Thin tumours were more likely to be diagnosed in the younger age groups and be classified as superficial spreading melanoma. In situ melanoma rates increased only slightly. Over the same time period, mortality rates have been relatively constant in both male and female subjects. Five-year relative survival varied from 91.8% (95% CI 90.4–93.1) for patients with thin tumours to 41.5% (95% CI 36.7–46.3) for those with thick tumours. In multivariable analyses, Breslow thickness was the most important prognostic factor. Age, sex and level of deprivation were also identified as independent prognostic factors. The trends in incidence suggest that the increase is real, rather than an artefact of increased scrutiny, implying that primary prevention in the Yorkshire area of the UK has failed to control trends in incidence. Mortality, in contrast, appears to be levelling off, indicating that secondary prevention has been more effective

Functional polymorphisms in the promoter regions of MMP2 and MMP3 are not associated with melanoma progression

<p>Abstract</p> <p>Background</p> <p>The matrix metalloproteinases (MMPs) are enzymes that cleave various components of the extracellular matrix (ECM) and basement membranes. MMPs are expressed in melanocytes and their overexpression has been linked to tumor development, progression and metastasis. At the genetic level, the following functional promoter polymorphisms are known to modify the gene transcription: -1306 C/T and -735 C/T in the MMP2 gene, and -1171 5A/6A in the MMP3 gene. Functional polymorphisms in MMP genes' promoter regions may modulate the risk for melanoma progression.</p> <p>Methods</p> <p>We evaluated MMP2 and MMP3 germline polymorphisms in a group of 1002 melanoma patients using PCR-based methods, including fragment size analysis and melting temperature profiles. Two-sided Chi-Square, Cochran-Armitage tests for trend, Fisher's exact tests, and Kendall's Tau tests were performed to evaluate the associations between genotype and various clinical and epidemiologic factors. Multivariate analyses were conducted using logistic regression, adjusting for known melanoma confounders such as age, sex, phenotypic index, moles, freckles, and race. Survival estimates were computed using the Kaplan-Meier method and differences in survival were assessed using the log rank test.</p> <p>Results</p> <p>All genotypes were in Hardy-Weinberg equilibrium. After adjustment for age, sex and phenotypic characteristics of melanoma risk, no significant associations were identified with the clinical, pathological, and epidemiological variables studied. The melting profile for MMP2 -735 C/T identified a new change in one sample. A new PCR-amplification followed by direct sequencing confirmed a heterozygote G to A substitution at position -729.</p> <p>Conclusion</p> <p>This study does not provide strong evidence for further investigation into the role of the MMP2 and MMP3 variants in melanoma progression.</p

Evaluating treatments in health care: The instability of a one-legged stool

<p>Abstract</p> <p>Background</p> <p>Both scientists and the public routinely refer to randomized controlled trials (RCTs) as being the 'gold standard' of scientific evidence. Although there is no question that placebo-controlled RCTs play a significant role in the evaluation of new pharmaceutical treatments, especially when it is important to rule out placebo effects, they have many inherent limitations which constrain their ability to inform medical decision making. The purpose of this paper is to raise questions about <it>over-reliance </it>on RCTs and to point out an additional perspective for evaluating healthcare evidence, as embodied in the Hill criteria. The arguments presented here are generally relevant to all areas of health care, though mental health applications provide the primary context for this essay.</p> <p>Discussion</p> <p>This article first traces the history of RCTs, and then evaluates five of their major limitations: they often lack external validity, they have the potential for increasing health risk in the general population, they are no less likely to overestimate treatment effects than many other methods, they make a relatively weak contribution to clinical practice, and they are excessively expensive (leading to several additional vulnerabilities in the quality of evidence produced). Next, the nine Hill criteria are presented and discussed as a richer approach to the evaluation of health care treatments. Reliance on these multi-faceted criteria requires more analytical thinking than simply examining RCT data, but will also enhance confidence in the evaluation of novel treatments.</p> <p>Summary</p> <p>Excessive reliance on RCTs tends to stifle funding of other types of research, and publication of other forms of evidence. We call upon our research and clinical colleagues to consider additional methods of evaluating data, such as the Hill criteria. Over-reliance on RCTs is similar to resting all of health care evidence on a one-legged stool.</p

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Female genital mutilation in the UK- where are we, where do we go next? Involving communities in setting the research agenda.

Female Genital Mutilation (FGM) is all practices involving cutting, alteration or injury to the female genitalia for non-medical reasons. It is a form of violence against women and children, with no benefits and many harms. In 2014, the UK Government committed to working to eliminate FGM. Steps taken towards this aim included creation of educational and safeguarding resources for professionals, and legislative changes including a mandatory reporting duty for professionals in England and Wales (where if a girl under 18 discloses or is found on examination to have FGM then the professional is mandated to report this to the police), and an FGM Enhanced Dataset applicable to NHS organisations in England requiring the submission of personal data about women and girls who have had FGM to NHS Digital. To date, compliance with dataset returns from primary care services have been low. This report describes using patient and public involvement (PPI) to identify research and service priorities to support communities affected by FGM.We held a series of PPI events (4 focus groups, and a multi-agency seminar) in 2015-2016, following the introduction of these legislative changes, speaking to community members, and professionals involved in their care. We asked participants to consider what they identified as research, knowledge and service priorities to support communities affected by FGM.The impact of these legislative and reporting requirements on the trust needed for community members to seek to consult health services was identified as important for further research. Priorities for service development were holistic services, that met a woman's needs throughout her lifecourse. Participants emphasised the importance of understanding how to listen, involve and utilise community voices in developing education for professionals, designing services, and developing policy.There was a desire for change to develop from within affected communities; any learning and resources need to be co-created and constructed in such a way that they can be effectively shared between women, communities, and professionals. Questions remain about how to define community consultation, how to recognise when it was adequate, and how to hear beyond community activists to hear a wider range of voices.variou

The relation between mortality from malignant melanoma and early detection in the Cancer Research Campaign Mole Watcher Study

Between 1987 and 1989 the Cancer Research Campaign funded a health education programme for the early detection of cutaneous malignant melanoma in the general population in 6 health districts of England and 1 health board in Scotland (population of 3 million). The intervention was evaluated by studying its effects on annual and cumulative mortality rates for melanoma. Population-based data on mortality from melanoma were collected in the intervention areas, the health regions covering those areas, and 5 other health regions of England from 1981 to 1996. Deaths from melanoma in cases diagnosed after the start of the intervention were used to study cumulative mortality rates. The annual mortality rates for melanoma, 1981 to 1996, showed no significant difference in their trends between the intervention areas, and other areas of England and Wales. After adjustment for pre-intervention rates, there was also no significant reduction in cumulative mortality from melanoma in the intervention areas compared with the non-intervention areas: rate ratio 1.2 (95% Cl 0.9–1.7) in men, 0.9 (95% Cl 0.7–1.3) in females. The lack of a significant reduction in melanoma mortality associated with the intervention raises questions about this approach to early detection and emphasises the need for new strategies. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Early efficacy of CABG care delivery in a low procedure-volume community hospital: operative and midterm results

BACKGROUND: The Leapfrog Group recommended that coronary artery bypass grafting (CABG) surgery should be done at high volume hospitals (>450 per year) without corresponding surgeon-volume criteria. The latter confounds procedure-volume effects substantially, and it is suggested that high surgeon-volume (>125 per year) rather than hospital-volume may be a more appropriate indicator of CABG quality. METHODS: We assessed 3-year isolated CABG morbidity and mortality outcomes at a low-volume hospital (LVH: 504 cases) and compared them to the corresponding Society of Thoracic Surgeons (STS) national data over the same period (2001–2003). All CABGs were performed by 5 high-volume surgeons (161–285 per year). "Best practice" care at LVH – including effective practice guidelines, protocols, data acquisition capabilities, case review process, dedicated facilities and support personnel – were closely modeled after a high-volume hospital served by the same surgeon-team. RESULTS: Operative mortality was similar for LVH and STS (OM: 2.38% vs. 2.53%), and the corresponding LVH observed-to-expected mortality (O/E = 0.81) indicated good quality relative to the STS risk model (O/E<1). Also, these results were consistent irrespective of risk category: O/E was 0, 0.9 and 1.03 for very-low risk (<1%), low risk (1–3%) and moderate-to-high risk category (>3%), respectively. Postoperative leg wound infections, ventilator hours, renal dysfunction (no dialysis), and atrial fibrillation were higher for LVH, but hospital stay was not. The unadjusted Kaplan-Meier survival for the LVH cohort was 96%, 94%, and 92% at one, two, and three years, respectively. CONCLUSION: Our results demonstrated that high quality CABG care can be achieved at LVH programs if 1) served by high volume surgeons and 2) patient care procedures similar to those of large programs are implemented. This approach may prove a useful paradigm to ensure high quality CABG care and early efficacy at low volume institutions that wish to comply with the Leapfrog standards

PPARβ activation inhibits melanoma cell proliferation involving repression of the Wilms’ tumour suppressor WT1

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that strongly influence molecular signalling in normal and cancer cells. Although increasing evidence suggests a role of PPARs in skin carcinogenesis, only expression of PPARγ has been investigated in human melanoma tissues. Activation of PPARα has been shown to inhibit the metastatic potential, whereas stimulation of PPARγ decreased melanoma cell proliferation. We show here that the third member of the PPAR family, PPARβ/δ is expressed in human melanoma samples. Specific pharmacological activation of PPARβ using GW0742 or GW501516 in low concentrations inhibits proliferation of human and murine melanoma cells. Inhibition of proliferation is accompanied by decreased expression of the Wilms’ tumour suppressor 1 (WT1), which is implicated in melanoma proliferation. We demonstrate that PPARβ directly represses WT1 as (1) PPARβ activation represses WT1 promoter activity; (2) in chromatin immunoprecipitation and electrophoretic mobility shift assays, we identified a binding element for PPARβ in the WT1 promoter; (3) deletion of this binding element abolishes repression by PPARβ and (4) the WT1 downstream molecules nestin and zyxin are down-regulated upon PPARβ activation. Our findings elucidate a novel mechanism of signalling by ligands of PPARβ, which leads to suppression of melanoma cell growth through direct repression of WT1