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This study sought to conduct a comprehensive search for genetic risk of cognitive decline in the context of geriatric depression.
A genome-wide association study (GWAS) analysis in the Neurocognitive Outcomes of Depression in the Elderly (NCODE) study.
Longitudinal, naturalistic follow-up study.
Older depressed adults, both outpatients and inpatients, receiving care at an academic medical center.
The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropsychological battery was administered to the study participants at baseline and a minimum of twice within a subsequent 3-year period in order to measure cognitive decline. A GWAS analysis was conducted to identify genetic variation that is associated with baseline and change in the CERAD Total Score (CERAD-TS) in NCODE.
The GWAS of baseline CERAD-TS revealed a significant association with an intergenic single-nucleotide polymorphism (SNP) on chromosome 6, rs17662598, that surpassed adjustment for multiple testing (p = 3.7 × 10−7; false discovery rate q = 0.0371). For each additional G allele, average baseline CERAD-TS decreased by 8.656 points. The most significant SNP that lies within a gene was rs11666579 in SLC27A1 (p = 1.1 × 10−5). Each additional copy of the G allele was associated with an average decrease of baseline CERAD-TS of 4.829 points. SLC27A1 is involved with processing docosahexaenoic acid (DHA), an endogenous neuroprotective compound in the brain. Decreased levels of DHA have been associated with the development of Alzheimer’s disease. The most significant SNP associated with CERAD-TS decline over time was rs73240021 in GRXCR1 (p = 1.1 × 10−6), a gene previously linked with deafness. However, none of the associations within genes survived adjustment for multiple testing.
Our GWAS of cognitive function and decline among individuals with late-life depression (LLD) has identified promising candidate genes that, upon replication in other cohorts of LLD, may be potential biomarkers for cognitive decline and suggests DHA supplementation as a possible therapy of interest.
Surface based MRI methods are a promising approach for the identification of cerebral shape alterations in schizophrenia . In particular, investigating gyrification might offer important evidence for disturbed neurodevelopmental mechanisms in schizophrenia.
The present study is the first to compare on a vertex - wise basis mean curvature as a sensitive parameter for the identification of local gyrification changes in first episode schizophrenia.
54 patients with first-episode schizophrenia and 54 healthy control subjects underwent high-resolution T1-weighted MRI scans. Surface extraction and mean curvature calculation was performed using the Freesurfer Software package. Statistical cortical maps were created to estimate gyrification differences between groups.
A significantly increased gyrification was detected in patients relative to controls in a large right parahippocampal-lingual cortex area. A further analysis of cortical thickness of this cluster revealed concurrent significant reduced cortical thickness in patients.
This is the first study to reveal an aberrant gyrification of the medial surface in first episode schizophrenia on basis of a vertex - wise analysis of local gyrification changes of the entire cortex. Both affected areas, the parahippocampal and the lingual cortex, are of high pathophysiological relevance for schizophrenia. Thus, our data provided new in vivo evidence for an early maturational deficit of these cortical areas in schizophrenia .
Depressive disorders are highly prevalent in the general population while there are marked diagnostic and therapeutic deficits resulting in direct and socioeconomic costs. Pharmacists represent important community facilitators in primary health care but their role in counselling and monitoring of depressed patients has rarely been investigated.
In order to improve knowledge about depressive disorders and practical skills, nationwide seminars were held for staff members [N=102] of German public pharmacies followed by an evaluation of personal views and seminar.
Personal estimates of proportion of depressed customers reached an extremely wide range from 1-70%. This view and further beliefs (regarding depression as an illness like any other; confidence in counselling) of pharmaceutical staff were correlated with age and years of practise rather than with professional position. Comprehensive education and specific training programmes (e.g. communication skills), especially in the younger and less experienced staff, may promote successful counselling of depressive individuals.
Mental health care systems need to more implement personnel of public pharmacies by training programmes to increase identification and treatment outcome of depression and reduction of health care expenses.
To validate the diagnosis of hyperkinetic disorders (HD) in the Danish Psychiatric Central Research Registry (DPCRR) for children and adolescents aged 4 to 15 given in the years 1995 to 2005.
From a total of 4568 participants, a representative random subsample of n = 387 patients were used to validate the diagnosis. Patient files were systematically scored for the presence of ICD-10 criteria for HD and oppositional defiant disorder/conduct disorder (ODD/CD; F91). Further to this, an inter-rater reliability study was also conducted, whereby two experienced child and adolescent psychiatrists who were blind to patients discharge diagnoses, rated a random subsample of n = 101 participants.
Information was available for 372 out of 387 patients. Out of n = 372 available files, n = 324 (86.8%) were evaluated to fulfil diagnostic criteria for HD. Due to missing information it was not possible to reach a conclusion for 5.1% of the cases, 3.8% of the diagnoses were registration errors, and in 4.3% of the files the diagnosis had to be rejected. Inter-rater agreement was high (κ = 0.83, z = 10.9, P < .001). The validity of hyperkinetic disorders, unspecified (F90.9) was lower and comorbid CD/ODD were under-diagnosed in the sample. All participants fulfilling HD criteria also fulfilled DSM-5-criteria for ADHD.
The risk of misclassification of patients with HD in the DPCRR is relatively low, with the exception of the diagnosis of hyperkinetic disorders, unspecified (F90.9).
Feeding management of the postnatal and preweaning calf has an important impact on calf growth and development during this critical period and affects the health and well-being of the calves. After birth, an immediate and sufficient colostrum supply is a prerequisite for successful calf rearing. Colostrum provides high amounts of nutrient as well as non-nutrient factors that promote the immune system and intestinal maturation of the calf. The maturation and function of the neonatal intestine enable the calf to digest and absorb the nutrients provided by colostrum and milk. Therefore, colostrum intake supports the start of anabolic processes in several tissues, stimulating postnatal body growth and organ development. After the colostrum feeding period, an intensive milk feeding protocol, that is, at least 20% of BW milk intake/day, is required to realise the calf potential for growth and organ development during the preweaning period. Insufficient milk intake delays postnatal growth and may have detrimental effects on organ development, for example, the intestine and the mammary gland. The somatotropic axis as the main postnatal endocrine regulatory system for body growth is stimulated by the intake of high amounts of colostrum and milk and indicates the promotion of anabolic metabolism in calves. The development of the forestomach is an important issue during the preweaning period in calves, and forestomach maturation is best achieved by solid feed intake. Unfortunately, intensive milk-feeding programmes compromise solid feed intake during the first weeks of life. In the more natural situation for beef calves, when milk and solid feed intake occurs at the same time, calves benefit from the high milk intake as evidenced by enhanced body growth and organ maturation without impaired forestomach development during weaning. To realise an intensive milk-feeding programme, it is recommended that the weaning process should not start too early and that solid feed intake should be at a high extent despite intensive milk feeding. A feeding concept based on intensive milk feeding prevents hunger and abnormal behaviour of the calves and fits the principles of animal welfare during preweaning calf rearing. Studies on milk performance in dairy cows indicate that feeding management during early calf rearing influences lifetime performance. Therefore, an intensive milk-feeding programme affects immediate as well as long-term performance, probably by programming metabolic pathways during the preweaning period.
To examine prenatal APAP exposure in relation to language development in offspring at 30 months of age.
A population-based pregnancy cohort study including 754 women who enrolled in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study in pregnancy week 8–13. Two exposure measures were used: (1) maternally reported number of APAP tablets taken between conception and enrollment; (2) APAP urinary concentration at enrollment. Language development at 30 months was assessed by nurse's evaluation and parental questionnaire, including the number of words the child used (<25, 25–50 and >50). Main study outcome; parental report of use of fewer than 50 words, termed language delay (LD).
59.2% of women enrolled in weeks 8–13 reported taking APAP between conception and enrollment. APAP was measurable in all urine samples and urinary APAP was correlated with the number of APAP taken during pregnancy (P<0.01). Language delay was more prevalent in boys (12.6%) than girls (4.1%) (8.5% in total). Both the number of APAP tablets and urinary APAP concentration were associated with greater LD in girls but not in boys. The adjusted odds ratio (OR) for LD among girls whose mothers reported >6 vs. 0 APAP tablets was 5.92 (95% confidence interval (CI) 1.10–31.94). The OR for LD in girls whose mothers’ urinary APAP was in the highest compared to the lowest quartile was 10.34 (95% CI 1.37–77.86). While it cannot be ruled out, our available data do not support confounding by indication.
Given the prevalence of prenatal APAP use and the importance of language development, these findings, if replicated, would suggest that pregnant women should limit their use of this analgesic during pregnancy.
We derive the surface and basal radar reflectance and backscatter coefficients of the southern McMurdo Ice Shelf (SMIS) and part of the nearby Ross Ice Shelf (RIS), Antarctica, from radar statistical reconnaissance using a 60-MHZ airborne survey. The surface coefficients are further inverted in terms of snow density and roughness, providing a spatial distribution of the processes contributing to the surface boundary conditions. We disentangle the basal coefficients from surface transmission losses, and we provide the basal coherent content, an indicator of the boundary geometric disorder that is also self-corrected from englacial attenuation. The basal radar properties exhibit sharp gradients along specific iso-depths, suggesting an abrupt modification of the ice composition and geometric structure. We interpret this behavior as locations where the pressure-melting point is reached, outlining fields of freezing and melting ice. Basal steps are observed at both SMIS and RIS, suggesting a common geometric expression of widespread basal processes. This technique offers a simultaneous view of both the surface and basal boundary conditions to help investigate the ice-shelf stability, while its application to airborne data significantly improves coverage of the difficult-to-observe ice–ocean boundary. It also provides constraints on thermohaline circulation in ice shelves cavities, which are analogs for ice-covered ocean worlds.
Identifying options for the sustainable intensification of cropping systems in southern Africa under prevailing high climate risk is needed. With this in mind, we tested an intercropping system that combined the staple crop maize with lablab, a local but underutilised legume. Grain and biomass productivity was determined for four variants (i) sole maize (sole-maize), (ii) sole lablab (sole-lablab), (iii) maize/lablab with both crops sown simultaneously (intercropped-SP) and (iv) maize/lablab with lablab sown 28 days after the maize crop (intercropped-DP). Soil water and weather data were monitored and evaluated. The trial was conducted for two seasons (2015/2016 and 2016/2017) at two sites in the Limpopo Province, South Africa: Univen (847 mm rainfall, 29.2 °C maximum and 18.9 °C minimum temperature average for the cropping season over the years 2008–2017) and Syferkuil (491 mm rainfall, with 27.0 °C maximum and 14.8 °C minimum temperature). Analysis revealed three key results: The treatment with intercropped-SP had significantly lower maize yields (2320 kg ha−1) compared with maize in intercropped-DP (2865 kg ha−1) or sole-maize (2623 kg ha−1). As expected, maize yields in the El Niño affected in season 2015/2016 were on average 1688 kg ha−1 lower than in 2016/2017. Maize yields were significantly lower (957 kg ha−1) at Univen, the warmer site with higher rainfall, than at Syferkuil. In 2015/2016, maximum temperature at Univen exceeded 40 °C around anthesis. Furthermore, soil water was close to the estimated permanent wilting point (PWP) for most of the cropping season, which indicates possible water limitations. In Syferkuil, the soil water was maintained well above PWP. Lablab yields were low, around 500 ha−1, but stable as they were not affected by treatment across season and site. Overall, the study demonstrated that intercropped-DP appears to use available soil water more efficiently than sole maize. Intercropped-DP could therefore be considered as an option for sustainable intensification under high climate risk and resource-limited conditions for smallholders in southern Africa.
Excessive mobilization of body reserves during the transition from pregnancy to lactation imposes a risk for metabolic diseases on dairy cows. We aimed to establish an experimental model for high v. normal mobilization and herein characterized performance, metabolic and endocrine changes from 7 weeks antepartum (a.p.) to 12 weeks postpartum (p.p.). Fifteen weeks a.p., 38 pregnant multiparous Holstein cows were allocated to two groups that were fed differently to reach either high or normal body condition scores (HBCS: 7.2 NEL MJ/kg dry matter (DM); NBCS: 6.8 NEL MJ/kg DM) at dry-off. Allocation was also based on differences in body condition score (BCS) in the previous and the ongoing lactation that was further promoted by feeding to reach the targeted BCS and back fat thickness (BFT) at dry-off (HBCS: >3.75 and >1.4 cm; NBCS: <3.5 and <1.2 cm). Thereafter, both groups were fed identical diets. Blood samples were drawn weekly from 7 weeks a.p. to 12 weeks p.p. to assess the serum concentrations of metabolites and hormones. The HBCS cows had greater BCS, BFT and BW than the NBCS cows throughout the study and lost more than twice as much BFT during the first 7 weeks p.p. compared with NCBS. Milk yield and composition were not different between groups, except that lactose concentrations were greater in NBSC than in HBCS. Feed intake was also greater in NBCS, and NBCS also reached a positive energy balance earlier than HBCS. The greater reduction in body mass in HBCS was accompanied by greater concentrations of non-esterified fatty acids, and β-hydroxybutyrate in serum after calving than in NBCS, indicating increased lipomobilization and ketogenesis. The mean concentrations of insulin across all time-points were greater in HBCS than in NBCS. In both groups, insulin and IGF-1 concentrations were lower p.p than in a.p. Greater free thyroxine (fT4) concentrations and a lower free 3-3′-5-triiodothyronine (fT3)/fT4 ratio were observed in HBCS than in NBCS a.p., whereas p.p. fT3/fT4 ratio followed a reverse pattern. The variables indicative for oxidative status had characteristic time courses; group differences were limited to greater plasma ferric reducing ability values in NBSC. The results demonstrate that the combination of pre-selection according to BCS and differential feeding before dry-off to promote the difference was successful in obtaining cows that differ in the intensity of mobilizing body reserves. The HBCS cows were metabolically challenged due to intense mobilization of body fat, associated with reduced early lactation dry matter intake and compromised antioxidative capacity.
Tail lesions caused by tail biting are a widespread welfare issue in pig husbandry. Determining their prevalence currently involves labour intensive, subjective scoring methods. Increased societal interest in tail lesions requires fast, reliable and cheap systems for assessing tail status. In the present study, we aimed to test the reliability of neural networks for assessing tail pictures from carcasses against trained human observers. Three trained observers scored tail lesions from automatically recorded pictures of 13 124 pigs. Nearly all pigs had been tail docked. Tail lesions were classified using a 4-point score (0=no lesion, to 3=severe lesion). In addition, total tail loss was recorded. Agreement between observers was tested prior and during the assessment in a total of seven inter-observer tests with 80 pictures each. We calculated agreement between observer pairs as exact agreement (%) and prevalence-adjusted bias-adjusted κ (PABAK; value 1=optimal agreement). Out of the 13 124 scored pictures, we used 80% for training and 20% for validating our neural networks. As the position of the tail in the pictures varied (high, low, left, right), we first trained a part detection network to find the tail in the picture and select a rectangular part of the picture which includes the tail. We then trained a classification network to categorise tail lesion severity using pictures scored by human observers whereby the classification network only analysed the selected picture parts. Median exact agreement between the three observers was 80% for tail lesions and 94% for tail loss. Median PABAK for tail lesions and loss were 0.75 and 0.87, respectively. The agreement between classification by the neural network and human observers was 74% for tail lesions and 95% for tail loss. In other words, the agreement between the networks and human observers were very similar to the agreement between human observers. The main reason for disagreement between observers and thereby higher variation in network training material were picture quality issues. Therefore, we expect even better results for neural network application to tail lesions if training is based on high quality pictures. Very reliable and repeatable tail lesion assessment from pictures would allow automated tail classification of all pigs slaughtered, which is something that some animal welfare labels would like to do.
The secondary instability in the wake of a two-dimensional blunt body with a chord to thickness ratio of 46.5 was experimentally investigated for Reynolds numbers of 3500, 5200 and 7000 based on the blunt trailing edge height
. Planar, stereoscopic and high-speed particle image velocimetry (PIV) measurements were performed to characterise the wake and upstream boundary layer. The same mode B secondary instability that is found in the cylinder wake was found to be present in the wake of the elongated body studied here. The most probable wavelength of the secondary instability, defined as the spanwise distance between adjacent streamwise vortex pairs in the wake, was found to range from
by applying a spatial autocorrelation to the spanwise–wall-normal instantaneous fields of the
-criterion. The temporal evolution of the secondary wake vortices was investigated using time-resolved stereoscopic PIV measurements and it was shown that the vortices maintain both their directions of rotation and spanwise positions during the primary vortex shedding cycles. In agreement with previous literature, the secondary instability did not greatly change as the upstream boundary layer transitioned from laminar to turbulent. Moreover, any upstream boundary layer structures were found to rapidly evolve into wake structures just past the blunt trailing edge. The wavelength of the secondary instability was shown to match the spanwise distance between adjacent low-speed zones of streamwise velocity in the wake. These undulating velocity patterns proved to be a viable method for determining the secondary instability wavelength; however, this type of analysis is highly sensitive to the energy content used for data reconstruction when proper orthogonal decomposition is applied beforehand.
Avian influenza virus (AIV) subtypes H5 and H7 can infect poultry causing low pathogenicity (LP) AI, but these LPAIVs may mutate to highly pathogenic AIV in chickens or turkeys causing high mortality, hence H5/H7 subtypes demand statutory intervention. Serological surveillance in the European Union provides evidence of H5/H7 AIV exposure in apparently healthy poultry. To identify the most sensitive screening method as the first step in an algorithm to provide evidence of H5/H7 AIV infection, the standard approach of H5/H7 antibody testing by haemagglutination inhibition (HI) was compared with an ELISA, which detects antibodies to all subtypes. Sera (n = 1055) from 74 commercial chicken flocks were tested by both methods. A Bayesian approach served to estimate diagnostic test sensitivities and specificities, without assuming any ‘gold standard’. Sensitivity and specificity of the ELISA was 97% and 99.8%, and for H5/H7 HI 43% and 99.8%, respectively, although H5/H7 HI sensitivity varied considerably between infected flocks. ELISA therefore provides superior sensitivity for the screening of chicken flocks as part of an algorithm, which subsequently utilises H5/H7 HI to identify infection by these two subtypes. With the calculated sensitivity and specificity, testing nine sera per flock is sufficient to detect a flock seroprevalence of 30% with 95% probability.
This article is a review of research on nanostructured high-entropy alloys with emphasis on those made by the severe plastic deformation methods of mechanical alloying and high-pressure torsion. An example of thin film refractory metal alloys made by magnetron sputtering is also presented. The article will begin with a discussion of the seminal research of B.S. Murty and co-workers who first produced nanocrystalline high-entropy alloys by mechanical alloying of powders. This will be followed by a listing of research, in mostly chronological order, of mainly 3d transition metal alloys made nanocrystalline by mechanical alloying. Research on the well-studied Cantor alloy, from the literature and the author’s laboratory will be presented. The author’s and co-worker’s research on a low-density high-entropy alloy with single-phase fcc or hcp structure and an extremely high strength (hardness)-to-weight ratio will be described.
Previous studies hypothesized that neurodevelopmental risk factors may play a role in the pathogenesis of obsessive-compulsive disorder (OCD). Cortical folding has been shown to be a reliable indicator for normal and altered neurodevelopment, but in OCD it has barely been investigated up to now. The present study investigates whether alterations in gyrification are detectable in OCD and, if so, how these are associated with clinical characteristics.
We compared the local Gyrification Index (lGI) between 75 OCD patients and 75 matched healthy subjects across the whole brain. In addition, for those regions exhibiting an altered lGI in patients we explored a potential relationship to symptom severity, age of onset, and influence of medication.
OCD patients had a significantly decreased lGI in right parietal, precentral but also insula, temporal, pars triangularis and rostral middle frontal regions compared to healthy subjects. A positive association with age of onset was found but no association with symptom severity. There was no effect of co-morbidity or medication.
The reduced gyrification found in OCD confirms previous findings in other psychiatric disorders and suggests that alterations may already occur during early stages of brain development. Our findings support the idea that altered cortical folding might represent a trait characteristic of the disorder although longitudinal studies are needed to clarify the trajectory of this morphological measure in OCD.
The incidence of childhood respiratory infections in Greenland is among the highest globally. We performed a population-based study of 352 Greenlandic children aged 0–6 years aiming to describe rates and risk factors for carriage of four key bacteria associated with respiratory infections, their antimicrobial susceptibility and inter-bacterial associations. Nasopharyngeal swabs were tested for Streptococcus pneumoniae grouped by serotypes included (VT) or not included (NVT) in the 13-valent pneumococcal conjugate vaccine, non-typable Haemophilus influenzae (NTHi), Staphylococcus aureus and Moraxella catarrhalis. S. pneumoniae was detected from age 2 weeks with a peak carriage rate of 60% in 2-year-olds. Young age and having siblings attending a daycare institution were associated with pneumococcal carriage. Overall co-colonization with ⩾2 of the studied bacteria was 52%. NTHi showed a positive association with NVT pneumococci and M. catarrhalis, respectively, M. catarrhalis was positively associated with S. pneumoniae, particular VT pneumococci, whereas S. aureus were negatively associated with NTHi and M. catarrhalis. Nasopharyngeal bacterial carriage was present unusually early in life and with frequent co-colonization. Domestic crowding increased odds of carriage. Due to important bacterial associations we suggest future surveillance of pneumococcal conjugate vaccine's impact on carriage in Greenland to also include other pathogens.
Natural disasters may have considerable impact on society as well as on the (re-)insurance industry. Max-stable processes are ideally suited for the modelling of the spatial extent of such extreme events, but it is often assumed that there is no temporal dependence. Only a few papers have introduced spatiotemporal max-stable models, extending the Smith, Schlather and Brown‒Resnick spatial processes. These models suffer from two major drawbacks: time plays a similar role to space and the temporal dynamics are not explicit. In order to overcome these defects, we introduce spatiotemporal max-stable models where we partly decouple the influence of time and space in their spectral representations. We introduce both continuous- and discrete-time versions. We then consider particular Markovian cases with a max-autoregressive representation and discuss their properties. Finally, we briefly propose an inference methodology which is tested through a simulation study.
We have used dedicated 0.7m telescopes in California and Israel to image the halos of ~ 200 galaxies in the Local Volume to 29 mag/sq arcsec, the sample mainly drawn from the 2MASS Large Galaxy Atlas (LGA). We supplement the LGA sample with dwarf galaxies and more distant giant ellipticals. Low surface brightness halos exceeding 50 kpc in diameter are found only in galaxies more luminous than L*, and classic interaction signatures are relatively infrequent. Halo diameter is correlated with total galaxy luminosity. Extended low surface brightness halos are present even in galaxies as faint as MV = - 18. Edge-on galaxies with boxy bulges tend to lack extended spheroidal halos, while those with large classical bulges exhibit extended round halos, supporting the notions that boxy or barlike bulges originate from disks. Most face-on spiral galaxies present features that appear to be irregular extensions of spiral arms, although rare cases show smooth boundaries with no sign of star formation. Although we serendipitously discovered a dwarf galaxy undergoing tidal disruption in the halo of NGC 4449, we found no comparable examples in our general survey. A search for similar examples in the Local Volume identified hcc087, a tidally disrupting dwarf galaxy in the Hercules Cluster, but we do not confirm an anomalously large half-light radius reported for the dwarf VCC 1661.
Conventional radiocarbon analysis of carbonate records with accelerator mass spectrometry (AMS) is time consuming and the achievable spatial resolution is limited, because individual samples have to be taken and need to be converted to graphite for the measurement. A new laser ablation (LA) in situ sampling technique for rapid online 14C analyses of carbonate records by AMS is presented. By focusing a 193-nm ArF excimer laser on carbonate samples, carbon dioxide is generated and can directly be introduced into the gas ion source of an AMS. A dedicated LA cell for AMS was constructed in a way that combines rapid gas exchange with the capacity to carry sample specimen with maximum dimensions of 15×2.5×1.5 cm3. With the presented setup, negative carbon ion currents up to 20 µA were achieved. A low 14C background of 0.011±0.002 F14C was observed on 14C-free marble and different standard and reference materials could be well reproduced within errors. The novel technique allows scanning carbonate samples continuously over several cm per hour with achievable measurement precisions of less than 1% for modern samples. This approach allows acquiring highly spatially resolved 14C records at a far higher rate than with any currently available method.
Nucleotide excision repair (NER) is a highly versatile and efficient DNA repair process, which is responsible for the removal of a large number of structurally diverse DNA lesions. Its extreme broad substrate specificity ranges from DNA damages formed upon exposure to ultraviolet radiation to numerous bulky DNA adducts induced by mutagenic environmental chemicals and cytotoxic drugs used in chemotherapy. Defective NER leads to serious diseases, such as xeroderma pigmentosum (XP). Eight XP complementation groups are known of which seven (XPA–XPG) are caused by mutations in genes involved in the NER process. The eighth gene, XPV, codes for the DNA polymerase ɳ, which replicates through DNA lesions in a process called translesion synthesis (TLS). Over the past decade, detailed structural information of these DNA repair proteins involved in eukaryotic NER and TLS have emerged. These structures allow us now to understand the molecular mechanism of the NER and TLS processes in quite some detail and we have begun to understand the broad substrate specificity of NER. In this review, we aim to highlight recent advances in the process of damage recognition and repair as well as damage tolerance by the XP proteins.