Fixational eye movement waveforms in amblyopia: Characteristics of fast and slow eye movements

Fixational eye movements comprise of fast microsaccades alternating with slow inter-saccadic drifts. These physiologic eye movements play an important role in visual perception.  Amblyopic patients are known to have fixation instability, particularly of the amblyopic eye. We examined eye movement abnormalities that contribute to this instability. We found that fixation stability is affected by the presence of fusion maldevelopment nystagmus (FMN). However, some amblyopes can have nystagmus without nasally directed slow phases and reversal in direction of the quick phase on ocular occlusion, features seen in FMN. In patients without nystagmus, we found increased amplitude of fixational saccades and inter-saccadic drifts. We categorized amblyopia patients by type (anisometropic, strabismic, or mixed) and eye movement waveform (no nystagmus, nystagmus without FMN, and FMN). We found specific fast and slow eye movement abnormalities of the fellow and amblyopic eye during fellow, amblyopic and both eyes viewing conditions across eye movement waveforms and types of amblyopia. These eye movement abnormalities can serve as biomarkers that can predict the impact of amblyopia as measured by visual acuity and stereopsis. Evaluation of fixational eye movements in amblyopia could be important to diagnose these common eye diseases and predict treatment effectiveness.&nbsp

Increased risk of HPV-associated genital cancers in men and women as a consequence of pre-invasive disease

To assess the excess risk of HPV‐associated cancer (HPVaC) in two at‐risk groups – women with a previous diagnosis of high grade cervical intraepithelial neoplasia (CIN3) and both men and women treated for non‐cervical pre‐invasive ano‐genital disease. All CIN3 cases diagnosed in 1989‐2015 in Scotland were extracted from the Scottish cancer registry (SMR06). All cases of pre‐invasive penile, anal, vulval, and vaginal disease diagnosed in 1990‐2015 were identified within the NHS pathology databases in the two largest NHS health boards in Scotland. Both were linked to SMR06 to extract subsequent incidence of HPVaC following the diagnosis of CIN3 or pre‐invasive disease. Standardised incidence ratios were calculated for the risk of acquiring HPVaC for the two at‐risk groups compared with the general Scottish population. Among 69714 females in Scotland diagnosed with CIN3 (890360.9 person‐years), 179 developed non‐cervical HPVaC. CIN3 cases were at 3.2‐fold (95% CI: 2.7 to 3.7) increased risk of developing non‐cervical HPVaC, compared to the general female population. Among 1235 patients diagnosed with non‐cervical pre‐invasive disease (9667.4 person‐years), 47 developed HPVaC. Individuals with non‐cervical pre‐invasive disease had a substantially increased risk of developing HPVaC ‐ 15.5‐fold (95% CI: 11.1 to 21.1) increased risk for females and 28‐fold (11.3 to 57.7) increased risk for males. We report a significant additional risk of HPV‐associated cancer in those have been diagnosed with pre‐invasive HPV‐associated lesions including but not confined to the cervix. Uncovering the natural history of pre‐invasive disease has potential for determining screening, prevention and treatment

Detection and Preservation of Biosignatures in Mars Analogs Hot Spring Deposits from the Taupo Volcanic Zone, New Zealand

Characterizing the preservation potential of biosignatures in martian analogs is essential in the quest for biosignatures with martian rovers. Hot spring silica deposits are part of the minerals with a high preservation potential. As part of an ongoing study, we are characterizing the nature and distribution of organic molecules including lipid biomarkers in a range of analog hot spring deposits, evaluating their preservation potential, and determining the potential signals from flight-like experiments. We are focusing on various geothermal fields in the New Zealand Taupo Volcanic Zone with physical and chemical variabilities. Samples are being extracted for lipid biomarker characterization as well as analysis using flight-like experiments from the current and future pyrolyzer-gas chromatographmass spectrometer instruments SAM and MOMA on the Curiosity and Exomars2020 rovers. The aim of work is to improve our knowledge of the detection and preservation of biosignatures in different hot spring lithologies while simultaneously evaluating the potential limits and biases of flight experiments.Fil: Millan, Maëva. University Of Georgetown; Estados Unidos. National Aeronautics and Space Administration; Estados UnidosFil: Campbell, Kathleen A.. Universidad Nacional y Kapodistriaca de Atenas; GreciaFil: Van Kranendonk, Martin J.. University of New South Wales; AustraliaFil: Sriaporn, Chanenath. Universidad Nacional y Kapodistriaca de Atenas; GreciaFil: Handley, Kim M.. Universidad Nacional y Kapodistriaca de Atenas; GreciaFil: Dobson, Michaela. Universidad Nacional y Kapodistriaca de Atenas; GreciaFil: Camp, Sîan. Universidad Nacional y Kapodistriaca de Atenas; GreciaFil: Teece, Bonnie. University of New South Wales; AustraliaFil: Guido, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Recursos Minerales. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto de Recursos Minerales; ArgentinaFil: Djokic, Tara. University of New South Wales; AustraliaFil: Farmer, Jack D.. Arizona State University; Estados UnidosFil: Stewart Johnson, Sarah. University Of Georgetown; Estados UnidosEPSC-DPS Joint Meeting 2019GenevaSuizaEuropean Process Safety Centr

HPV status and favorable outcome in vulvar squamous cancer

It is universally accepted that high-risk human papillomavirus (HR-HPV) is the cause of cervical dysplasia and cancer. More recently, it has been shown that HPV is also a marker of clinical outcome in oropharyngeal cancer. However, contemporary information is lacking on both the prevalence of HPV infection in vulvar cancer (VSCC), its precursor lesion, vulvar intraepithelial neoplasia (VIN) and the influence of HPV-status on the prognosis of this malignancy. We have conducted a detailed population-based study to examine rates of progression of VIN to VSCC, type-specific HPV prevalence in vulvar disease and the influence of HPV status on clinical outcome in VSCC. We observed that the age at which women are diagnosed with VSCC is falling and there is a significant time gap between first diagnosis of VIN and progression to invasive disease. HR-HPV infection was detected in 87% (97/112) cases of VIN and 52% cases (32/62) of VSCC. The presence of HR-HPV in squamous intraepithelial lesion was associated with lower rates of progression to invasive cancer (hazard ratio, 0.22, p = 0.001). In the adjusted analysis, HR-HPV was associated with improved progression-free survival of VSCC compared to those with HPV negative tumours (hazard ratio, 0.32, p = 0.02)

HPV status and favorable outcome in vulvar squamous cancer

It is universally accepted that high-risk human papillomavirus (HR-HPV) is the cause of cervical dysplasia and cancer. More recently it has been shown that HPV is also a marker of clinical outcome in oropharyngeal cancer. However, contemporary information is lacking on both the prevalence of HPV infection in vulvar cancer (VSCC), its precursor lesion, vulvar intraepithelial neoplasia (VIN) and the influence of HPV-status on the prognosis of this malignancy. We have conducted a detailed population-based study to examine rates of progression of VIN to VSCC, type-specific HPV prevalence in vulvar disease and the influence of HPV status on clinical outcome in VSCC. We observed that the age at which women are diagnosed with VSCC is falling and there is a significant time gap between first diagnosis of VIN and progression to invasive disease. HR-HPV infection was detected in 87% (97/112) cases of VIN and 52% cases (32/62) of VSCC. The presence of HR-HPV in squamous intraepithelial lesion was associated with lower rates of progression to invasive cancer (hazard ratio, 0.22, p=0.001). In the adjusted analysis, HR-HPV was associated with improved progression-free survival of VSCC compared to those with HPV negative tumours (hazard ratio, 0.32, p=0.02)

Influence of COMT genotype and affective distractors on the processing of self-generated thought

The catechol-O-methyltransferase (COMT) enzyme is a major determinant of prefrontal dopamine levels. The Val158Met polymorphism affects COMT enzymatic activity and has been associated with variation in executive function and affective processing. This study investigated the effect of COMT genotype on the flexible modulation of the balance between processing self-generated and processing stimulus-oriented information, in the presence or absence of affective distractors. Analyses included 124 healthy adult participants, who were also assessed on standard working memory (WM) tasks. Relative to Val carriers, Met homozygotes made fewer errors when selecting and manipulating self-generated thoughts. This effect was partly accounted for by an association between COMT genotype and visuospatial WM performance. We also observed a complex interaction between the influence of affective distractors, genotype and sex on task accuracy: male, but not female, participants showed sensitivity to the affective distractors that was dependent on COMT genotype. This was not accounted for by WM performance. This study provides novel evidence of the role of dopaminergic genetic variation on the ability to select and manipulate self-generated thoughts. The results also suggest sexually dimorphic effects of COMT genotype on the influence of affective distractors on executive function

De novo variants of NR4A2 are associated with neurodevelopmental disorder and epilepsy

Purpose This study characterizes the clinical and genetic features of nine unrelated patients with de novo variants in the NR4A2 gene. Methods Variants were identified and de novo origins were confirmed through trio exome sequencing in all but one patient. Targeted RNA sequencing was performed for one variant to confirm its splicing effect. Independent discoveries were shared through GeneMatcher. Results Missense and loss-of-function variants in NR4A2 were identified in patients from eight unrelated families. One patient carried a larger deletion including adjacent genes. The cases presented with developmental delay, hypotonia (six cases), and epilepsy (six cases). De novo status was confirmed for eight patients. One variant was demonstrated to affect splicing and result in expression of abnormal transcripts likely subject to nonsense-mediated decay. Conclusion Our study underscores the importance of NR4A2 as a disease gene for neurodevelopmental disorders and epilepsy. The identified variants are likely causative of the seizures and additional developmental phenotypes in these patients

The driver mutational landscape of ovarian squamous cell carcinomas arising in mature cystic teratoma

Purpose. We sought to identify the genomic abnormalities in squamous cell carcinomas (SCC) arising in ovarian mature cystic teratoma (MCT), a rare gynaecological malignancy of poor prognosis. Experimental design. We performed copy number, mutational state and zygosity analysis of 151 genes in SCC arising in MCT (n=25) using next-generation sequencing. The presence of high/intermediate risk HPV genotypes was assessed by quantitative PCR. Genomic events were correlated with clinical features and outcome Results. MCT had a low mutation burden with a mean of only 1 mutation per case. Zygosity analyses of MCT indicated four separate patterns, suggesting that MCT can arise from errors at various stages of oogenesis. A total of 244 abnormalities were identified in 79 genes in MCT-associated SCC, and the overall mutational burden was high (mean 10.2 mutations per megabase). No SCC was positive for HPV. The most frequently altered genes in SCC were TP53 (20/25 cases, 80%), PIK3CA (13/25 cases, 52%) and CDKN2A (11/25 cases, 44%). Mutation in TP53 was associated with improved overall survival. In 8/20 cases with TP53 mutations, two or more variants were identified, which were bi-allelic. Conclusions. Ovarian SCC arising in MCT has a high mutational burden with TP53 mutation the most common abnormality. The presence TP53 mutation is a good prognostic factor. SCC arising in MCT share similar mutation profiles to other SCC. Given their rarity, they should be included in basket studies that recruit patients with SCC of other organs