Deriving null functional heads: a study on variation of functional structure

The aim of this dissertation is to develop a framework of functional structure that ensures that the representation of any phrase is only as large as necessary to capture the syntactic relations relevant to it. I argue that the success of this project requires the elimination of null functional heads from the lexicon. Rather, I propose that null functional heads and their projections are dynamically created during the derivation as an extension of the projection of lexical items (i.e. lexical heads and overt functional heads). To this end, I make two proposals. Firstly, I argue that the featural specifications of lexical items are more extensive and have a more complex structure than previously thought. Secondly, I refine Giorgi and Pianesi’s (1997) Feature Scattering operation so that it applies to entire segments of a featural specification, instead of individual features. One beneficial implication of this formulation is that it reduces head movement to the incidental scattering of the phonological features of a head due to independent syntactic factors. Hence, I present an analysis of a number of cases of head movement in support of the proposed framework of functional structure. Amongst other things, I address V-to-v movement (as in the case of English main verbs), V-to-T movement (as in the case of Romance verbs and English auxiliaries) and V-to-C movement (as in the case of Germanic V2 and English residual V2). Additionally, I extend the analysis to cases of head movement to an initial position, including the movement of the verb in verb-initial clauses and the movement of the noun in noun-initial nominal phrases in Semitic and Celtic languages, which have previously received little attention in the strand of research that adopts Feature Scattering or other similar re-projective mechanisms. Beyond head movement, I develop a uniform analysis of various subject/non-subject asymmetries, including Subject Auxiliary Inversion and do-support in English wh-questions and the that-trace effect in English embedded clauses involving wh-extraction, with the intention to bring the relevant phenomena to bear on the overarching hypothesis that functional structure is variable

Effectiveness of an image analyzing AI-based Digital Health Technology to identify Non-Melanoma Skin Cancer and other skin lesions: results of the DERM-003 study

IntroductionIdentification of skin cancer by an Artificial Intelligence (AI)-based Digital Health Technology could help improve the triage and management of suspicious skin lesions.MethodsThe DERM-003 study (NCT04116983) was a prospective, multi-center, single-arm, masked study that aimed to demonstrate the effectiveness of an AI as a Medical Device (AIaMD) to identify Squamous Cell Carcinoma (SCC), Basal Cell Carcinoma (BCC), pre-malignant and benign lesions from dermoscopic images of suspicious skin lesions. Suspicious skin lesions that were suitable for photography were photographed with 3 smartphone cameras (iPhone 6S, iPhone 11, Samsung 10) with a DL1 dermoscopic lens attachment. Dermatologists provided clinical diagnoses and histopathology results were obtained for biopsied lesions. Each image was assessed by the AIaMD and the output compared to the ground truth diagnosis.Results572 patients (49.5% female, mean age 68.5 years, 96.9% Fitzpatrick skin types I-III) were recruited from 4 UK NHS Trusts, providing images of 611 suspicious lesions. 395 (64.6%) lesions were biopsied; 47 (11%) were diagnosed as SCC and 184 (44%) as BCC. The AIaMD AUROC on images taken by iPhone 6S was 0.88 (95% CI: 0.83–0.93) for SCC and 0.87 (95% CI: 0.84–0.91) for BCC. For Samsung 10 the AUROCs were 0.85 (95% CI: 0.79–0.90) and 0.87 (95% CI, 0.83–0.90), and for the iPhone 11 they were 0.88 (95% CI, 0.84–0.93) and 0.89 (95% CI, 0.86–0.92) for SCC and BCC, respectively. Using pre-determined diagnostic thresholds on images taken on the iPhone 6S the AIaMD achieved a sensitivity and specificity of 98% (95% CI, 88–100%) and 38% (95% CI, 33–44%) for SCC; and 94% (95% CI, 90–97%) and 28% (95 CI, 21–35%) for BCC. All 16 lesions diagnosed as melanoma in the study were correctly classified by the AIaMD.DiscussionThe AIaMD has the potential to support the timely diagnosis of malignant and premalignant skin lesions

Wound healing protects against chemotherapy-induced alopecia in young rats via up-regulating interleukin-1β-mediated signaling

YesWound healing is a complex process regulated by various cell types and a plethora of mediators. While interactions between wounded skin and the hair follicles (HFs) could induce HF neogenesis or promote wound healing, it remains unknown whether the wound healing-associated signaling milieu can be manipulated to protect against alopecia, such as chemotherapy-induced alopecia (CIA). Utilizing a well-established neonatal rat model of CIA, we show here that skin wounding protects from alopecia caused by several clinically relevant chemotherapeutic regimens, and that protection is dependent on the time of wounding and hair cycle stage. Gene expression profiling unveiled a significant increase in interleukin-1 beta (IL-1β) mediated signaling by skin wounding. Subsequently, we showed that IL-1β is sufficient and indispensable for mediating the CIA-protective effect. Administration of IL-1β alone to unwounded rats exhibited local CIA protection while IL-1β neutralization abrogated CIA protection by wounding. Mechanistically, IL-1β retarded postnatal HF morphogenesis, making HFs at the wound sites or IL-1β treated areas damage-resistant while the rats developed total alopecia elsewhere. We conclude that wound healing switches the cutaneous cytokine milieu to an IL-1β-dominated state thus retarding HF growth progression and rendering the HFs resistant to chemotherapy agents. In the future, manipulation of HF progression through interfering with the IL-1β signaling milieu may provide therapeutic benefits to a variety of conditions, from prevention of CIA to inhibition of hair growth and treatment of hirsutism

Genome-wide association study in frontal fibrosing alopecia identifies four susceptibility loci including HLA-B*07:02

Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis. We observe genome-wide significant association with FFA at four genomic loci: 2p22.2, 6p21.1, 8q24.22 and 15q2.1. Within the 6p21.1 locus, fine-mapping indicates that the association is driven by the HLA-B*07:02 allele. At 2p22.1, we implicate a putative causal missense variant in CYP1B1, encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlights overrepresentation of transcripts encoding components of innate and adaptive immune response pathways. These findings provide insight into disease pathogenesis and characterise FFA as a genetically predisposed immuno-inflammatory disorder driven by HLA-B*07:02

Subject/non-subject asymmetries in the distribution of complementizers in English

In this dissertation I return to an old question within the generative grammar tradition, the that-trace effect: the incompatibility of the overt complementizer that with extraction from a subject position in an English embedded declarative clause. In common with other approaches to the that-trace effect, my analysis will place the that-trace effect within the larger context of the complementizer system of English. However, my main comparison will be with a similar pattern which I will call the ‘anti-that-trace effect: in non-wh relative clauses the null realization of the complementizer is incompatible with relativization over a subject. The two phenomena display a common characteristic which should not go unnoticed: a subject/non-subject asymmetry which is quite unique amongst the various phenomena that display restrictions in the distribution of complementizers. I argue that this empirical observation begs for a uniform analysis of the two phenomena. To achieve this I propose that the left periphery of an embedded clause encodes the semantic property of (non)-referentiality, which is structurally determined by the movement of the subject to the CP domain and which is phonologically realized in the overt/null form of the complementizer. Therefore, subject/non-subject asymmetries in the distribution of complementizers appear when the independent movement operations of extraction or relativization interfere with this mechanism. Furthermore, the contrast between the null-C requirement of the that-trace effect versus the overt-C requirement of the anti-that-trace effect is captured by the proposal that relativized nominals are featurally impoverished in comparison to a regular DP or a wh-phrase