Reading Difficulties in Individuals with Homonymous Visual Field Defects: A Systematic Review of Reported Interventions.

Reading difficulties are amongst the most commonly reported problems in individuals with homonymous visual field defects (HVFDs). To be able to provide guidance for healthcare professionals considering offering reading training, researchers in this field and interested individuals with HVFDs, this systematic review aims to (1) provide an overview of the contextual and intervention characteristics of all published HVFD interventions and (2) generate insights into the different reading outcome measures that these studies adopted. A search on PsycINFO, MEDLINE and Web of Science was conducted up to February 2, 2023. All intervention studies for HVFD in which reading was measured were included. Data was collected about the intervention type, session duration, number of sessions, the intensity, duration, circumstance of the interventions, country in which the intervention was studied and reading measures. Sixty records are included, describing 70 interventions in total of which 21 are specifically reading interventions. Overall, adjusted saccadic behaviour interventions occur most in the literature. A wide range within all intervention characteristics was observed. Forty-nine records reported task-performance reading measures, and 33 records reported self-reported reading measures. The majority of task-performance measures are based on self-developed paragraph reading tasks with a time-based outcome measure (e.g. words per minute). Future research could benefit from making use of validated reading tests, approaching the measurement of reading mixed-methods and providing participants the possibility to supply outcomes relevant to them.

Neurovisual rehabilitation in multiple sclerosis: Why a close integration of low-vision rehabilitation and neuropsychological rehabilitation may be effective for visual complaints.

OBJECTIVE: The quality of life of people with multiple sclerosis (MS) is often affected by visual complaints. A previous study suggested that visual complaints are not likely to be related to specific visual functions, but by a global decline of cognitive and visual functioning. In this study, we further explore this hypothesis, by investigating the relation between visual functions and global cognitive functioning, aiming to provide recommendations for rehabilitation for visual complaints. DESIGN: Cross-sectional study. SETTING: A rehabilitation centre for partially sighted and blind people and a MS centre at a university hospital. PARTICIPANTS: 102 people with MS. MAIN MEASURE: Correlations between assessments of visual functions (acuity, contrast sensitivity, visual field, smooth pursuit and saccades) and composite scores of a neuropsychological assessment (tests with a visual component and without a visual component). RESULTS: All composite scores correlated with visual acuity, contrast sensitivity and the sensitivity of the monocular field, but not with smooth pursuit and saccades. Similar patterns were found in various subgroups. Results showed that visual functions that related to visual complaints correlated with a diffuse decline of global cognitive functioning and that visual and cognitive functioning may decline concurrently in people with MS. CONCLUSIONS: Visual complaints may occur as a result of a diffuse decline of the integrity of a cerebral network involved in vision and cognition. People with MS with visual complaints may benefit from neurovisual rehabilitation, in which low-vision rehabilitation and neuropsychological rehabilitation are closely intertwined.

The complex relation between visual complaints and decline in visual, visuoperceptual and cognitive functions in people with multiple sclerosis.

People with multiple sclerosis (pwMS) report many different visual complaints, but not all of them are well understood. Decline in visual, visuoperceptual and cognitive functions do occur in pwMS, but it is unclear to what extend those help us understand visual complaints. The purpose of this cross-sectional study was to explore the relation between visual complaints and decline in visual, visuoperceptual and cognitive functions, to optimize care for pwMS. Visual, visuoperceptual and cognitive functions of 68 pwMS with visual complaints and 37 pwMS with no or minimal visual complaints were assessed. The frequency of functional decline was compared between the two groups and correlations were calculated between visual complaints and the assessed functions. Decline in several functions occurred more frequently in pwMS with visual complaints. Visual complaints may be an indication of declined visual or cognitive functioning. However, as most correlations were not significant or weak, we cannot infer that visual complaints are directly related to functions. The relationship may be indirect and more complex. Future research could focus on the overarching cognitive capacity that may contribute to visual complaints. Further research into these and other explanations for visual complaints could help us to provide appropriate care for pwMS.

Ultrafast laser-induced strain waves in thin ruthenium layers.

We report on the time-dependent optical diffraction from ultra-high frequency laser-induced acoustic waves in thin layers of ruthenium deposited on glass substrates. We show that the thermo-optic and strain-optic effects dominate the optical response of Ru layers to a traveling longitudinal strain wave. In addition, we show the generation and detection of acoustic waves with a central frequency ranging from 130 GHz to 750 GHz on ultra-thin layers with thicknesses in the range of 1.2 - 20 nm. For these ultra-thin layers we measure a strong dependency of the speed of sound on the layer thickness and, thus, the frequency. This frequency-dependent speed of sound results in a frequency-dependent acoustic impedance mismatch between the ruthenium and the glass substrate, leading to a faster decay of the measured signals for increasing frequency. Furthermore, for these extremely high-frequency oscillations, we find that the frequency and phase remain constant for times longer than about 2 ps after optical excitation. Back extrapolation of the acquired acoustic signals to t = 0 gives a starting phase of -π/2. As this seems unlikely, we interpret this as an indication of possible dynamic changes in the phase/frequency of the acoustic wave in the first 2 ps after excitation.

Femtosecond time-resolved pump-probe measurements on percolating gold in the ablation regime.

We report on femtosecond laser ablation experiments on percolating gold layers deposited on a glass substrate. In our experiments, we measure changes in optical transmission and reflection induced by single, high-intensity infrared laser pulses as a function of the time delay between the pump and the probe. For the highest pump intensities we find that on a time scale of about 150 ps after excitation, the transmission and reflection approach values close to the substrate values. We attribute this rapid ablation to vaporization of the entire layer when the injected energy exceeds the cohesive energy of the material. This vaporization results in the rapid transformation of the gold layer into a sufficiently dilute mist of atoms and nano-particles which renders the material almost optically transparent to the probe pulse. SEM images of the surfaces show how the morphology of the films changes at relatively low excitation intensities and show the complete removal of the gold at high intensities. We find that the ablation threshold for percolating Au on glass is 2.3 × 1011 W/cm2, which is two orders of magnitude lower than the damage threshold for continuous gold layers as reported in the literature.

Lacosamide monotherapy in clinical practice: A retrospective chart review.

OBJECTIVE: To assess effectiveness and tolerability of first-line and conversion to lacosamide monotherapy for focal seizures. MATERIALS AND METHODS: Retrospective, non-interventional chart review of lacosamide monotherapy patients aged ≥16 years in Europe. Outcomes included retention rate at observational point (OP) 3 (12 ± 3 months), seizure freedom rates at OP2 (6 ± 3 months) and OP3 and adverse drug reactions (ADRs). RESULTS: A total of 439 patients were included (98 first-line and 341 conversion to monotherapy; 128 aged ≥65 years [25 first-line and 103 conversion to monotherapy]). First-line and conversion to monotherapy retention rates were 60.2% (59/98; 95% confidence interval [CI] 49.8%-70.0%) and 62.5% (213/341; 57.1%-67.6%), respectively. Kaplan-Meier estimates of 12-month retention rates were 81.2% and 91.4% for first-line and conversion to monotherapy, respectively. First-line and conversion to monotherapy retention rates in patients aged ≥65 years were 60.0% (38.7%-78.9%) and 68.9% (59.1%-77.7%), respectively. At OP2, 66.3% of first-line and 63.0% of conversion to monotherapy patients were seizure free. At OP3, 60.2% of first-line and 52.5% of conversion to monotherapy patients were seizure free. In the ≥65 years subgroup, seizure freedom rates at OP2 were 72.0% and 68.0% for first-line and converted to monotherapy, respectively, and at OP3, 68.0% and 56.3%, respectively. Overall, 52 of 439 (11.8%) patients reported ADRs (16.4% in ≥65 years subgroup), most commonly dizziness (5.0%), headache (2.1%) and somnolence (1.6%). CONCLUSIONS: Lacosamide was effective and well tolerated as first-line or conversion to monotherapy in a clinical setting in adult and elderly patients with focal seizures.

Electro-clinical criteria and surgical outcome: Is there a difference between mesial and lesional temporal lobe epilepsy?

OBJECTIVES: Mesial temporal lobe epilepsy syndrome (MTLE) with specific electrophysiological and clinical characteristics and hippocampal sclerosis (HS) on MRI is considered the prototype of a syndrome with good surgical prognosis. Ictal onset zones in MTLE have been found to extend outside the hippocampus and neocortical seizures often involve mesial structures. It can, thus, be questioned whether MTLE with HS is different from lesional temporal epilepsies with respect to electro-clinical characteristics and surgical prognosis. We assessed whether MTLE with HS is distinguishable from lesional TLE and which criteria determine surgical outcome. METHODS: People in a retrospective cohort of 389 individuals with MRI abnormalities who underwent temporal lobectomy, were divided into "HS only" or "lesional" TLEs. Twenty-six presented with dual pathology and were excluded from further analysis. We compared surgical outcome and electro-clinical characteristics. RESULTS: Over half (61%) had "HS only." Four electro-clinical characteristics (age at epilepsy onset, febrile seizures, memory dysfunction and contralateral dystonic posturing) distinguished "HS only" from "lesional" TLE, but there was considerable overlap. Seizure freedom 2 years after surgery (Engel class 1) was similar: 67% ("HS only") vs 69% ("lesional" TLE). Neither presence of HS nor electro-clinical criteria was associated with surgical outcome. CONCLUSIONS: Despite small differences in electrophysiological and clinical characteristics between MTLE with HS and lesional TLE, surgical outcomes are similar, indicating that aetiology seems irrelevant in the referral for temporal surgery.

Epidemiology, pathophysiology and putative genetic basis of carbamazepine- and oxcarbazepine-induced hyponatremia.

The use of carbamazepine (CBZ) and oxcarbazepine (OXC) as first-line antiepileptic drugs in the treatment of focal epilepsy is limited by hyponatremia, a known adverse effect. Hyponatremia occurs in up to half of people taking CBZ or OXC and, although often assumed to be asymptomatic, it can lead to symptoms ranging from unsteadiness and mild confusion to seizures and coma. Hyponatremia is probably due to the antidiuretic properties of CBZ and OXC that are, at least partly, explained by stimulation of the vasopressin 2 receptor/aquaporin 2 pathway. No known genetic risk variants for CBZ- and OXC-induced hyponatremia exist, but likely candidate genes are part of the vasopressin water reabsorption pathway.

Efficient nucleus detector in histopathology images.

In traditional cancer diagnosis, (histo)pathological images of biopsy samples are visually analysed by pathologists. However, this judgment is subjective and leads to variability among pathologists. Digital scanners may enable automated objective assessment, improved quality and reduced throughput time. Nucleus detection is seen as the corner stone for a range of applications in automated assessment of (histo)pathological images. In this paper, we propose an efficient nucleus detector designed with machine learning. We applied colour deconvolution to reconstruct each applied stain. Next, we constructed a large feature set and modified AdaBoost to create two detectors, focused on different characteristics in appearance of nuclei. The proposed modification of AdaBoost enables inclusion of the computational cost of each feature during selection, thus improving the computational efficiency of the resulting detectors. The outputs of the two detectors are merged by a globally optimal active contour algorithm to refine the border of the detected nuclei. With a detection rate of 95% (on average 58 incorrectly found objects per field-of-view) based on 51 field-of-view images of Her2 immunohistochemistry stained breast tissue and a complete analysis in 1 s per field-of-view, our nucleus detector shows good performance and could enable a range of applications in automated assessment of (histo)pathological images.

An automatic vision-based malaria diagnosis system.

Malaria is a worldwide health problem with 225 million infections each year. A fast and easy-to-use method, with high performance is required to differentiate malaria from non-malarial fevers. Manual examination of blood smears is currently the gold standard, but it is time-consuming, labour-intensive, requires skilled microscopists and the sensitivity of the method depends heavily on the skills of the microscopist. We propose an easy-to-use, quantitative cartridge-scanner system for vision-based malaria diagnosis, focusing on low malaria parasite densities. We have used special finger-prick cartridges filled with acridine orange to obtain a thin blood film and a dedicated scanner to image the cartridge. Using supervised learning, we have built a Plasmodium falciparum detector. A two-step approach was used to first segment potentially interesting areas, which are then analysed in more detail. The performance of the detector was validated using 5,420 manually annotated parasite images from malaria parasite culture in medium, as well as using 40 cartridges of 11,780 images containing healthy blood. From finger prick to result, the prototype cartridge-scanner system gave a quantitative diagnosis in 16 min, of which only 1 min required manual interaction of basic operations. It does not require a wet lab or a skilled operator and provides parasite images for manual review and quality control. In healthy samples, the image analysis part of the system achieved an overall specificity of 99.999978% at the level of (infected) red blood cells, resulting in at most seven false positives per microlitre. Furthermore, the system showed a sensitivity of 75% at the cell level, enabling the detection of low parasite densities in a fast and easy-to-use manner. A field trial in Chittagong (Bangladesh) indicated that future work should primarily focus on improving the filling process of the cartridge and the focus control part of the scanner.

Hyperactive behavior in a family with autosomal dominant lateral temporal lobe epilepsy caused by a mutation in the LGI1/epitempin gene.

Autosomal dominant lateral temporal lobe epilepsy (ADLTE) is characterized by focal seizures with auditory features or aphasia. Mutations in the leucine-rich glioma-inactivated 1 (LGI1) gene have been reported in up to 50% of families with ADLTE. Attention-deficit/hyperactivity disorder (ADHD) symptoms have not yet been reported in these families. Clinical data were collected from a family with five affected members. Leucine-rich glioma-inactivated 1 exons and boundaries were sequenced by standard methods. Attention-deficit/hyperactivity disorder symptoms were scored based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Affected members had seizures with auditory features and psychic auras, and some experienced nightmares. A heterozygous c.431+1G>A substitution in LGI1 was detected in all members. Significantly more hyperactivity symptoms were found in family members carrying the LGI1 mutation. This study expands the phenotypic spectrum associated with ADLTE due to LGI1 mutation and underlines the need for more systematic evaluation of ADHD and related symptoms.

SPTLC1 is mutated in hereditary sensory neuropathy, type 1.

Hereditary sensory neuropathy type 1 (HSN1, MIM 162400; ref. 1) genetically maps to human chromosome 9q22 (refs. 2-4). We report here that the gene encoding a subunit of serine palmitoyltransferase is located within the HSN1 locus, expressed in dorsal root ganglia (DRG) and mutated in HSN1.

Recognizing visual complaints in people with multiple sclerosis: Prevalence, nature and associations with key characteristics of MS.

BACKGROUND: Visual disturbances are common in multiple sclerosis (MS), but visual complaints may be underestimated. While these complaints decrease quality of life, they may not be discussed during clinic visits. People with MS (pwMS) may not be referred to appropriate care. We therefore investigated the prevalence, nature and associations of visual complaints of pwMS. METHODS: We performed a cohort study with a comparison group. PwMS (n = 493) and healthy controls (n = 661) filled out the Screening Visual Complaints questionnaire (SVCq). Primary outcomes were the percentage of pwMS and controls that reported the 19 complaints, and total scores of the SVCq. We also compared the scores on the SVCq between different groups of pwMS. RESULTS: In general, the complaints were reported more often by pwMS than by controls. PwMS especially reported experiencing complaints 'often/always', while controls reported the complaints primarily 'sometimes'. PwMS with and without a history of optic neuritis showed similar complaints. PwMS with a longer disease duration and those with SPMS reported more complaints. EDSS score and disease duration only showed a limited association with discomfort of visual complaints. CONCLUSION: The prevalence of visual complaints among pwMS is high and any person with MS may experience a wide array of different visual complaints anywhere along the disease course, regardless of a history of optic neuritis. Using the SVCq may help detect pwMS' visual complaints and may facilitate referrals to appropriate care.

Intrinsic and extrinsic control of hemopoietic stem cell numbers: mapping of a stem cell gene.

We evaluated in vivo interactions between extrinsic (growth factor induced) and intrinsic (genetically determined) effectors of mouse primitive hemopoietic stem cell proliferation and numbers. Accordingly, stem cell frequency and cell cycle kinetics were assessed in eight strains of inbred mice using the cobblestone area-forming cell (CAFC) assay. A strong inverse correlation was observed between mouse lifespan and the number of autonomously cycling progenitors (CAFC day 7) in the femur. The population size of primitive stem cells (CAFC day 35) varied widely (up to sevenfold) among strains, unlike total CAFC day 7 numbers (cycling and quiescent), which were similar. Administration of the early acting cytokine flt-3 ligand to these strains resulted in activation of quiescent primitive stem cells exclusively in strains with high endogenous stem cell numbers (DBA and AKR), but was unrelated to strain-specific progenitor cell cycling. To map loci affecting stem cell frequency, we quantified stem cells in BXD recombinant inbred mice (offspring of C57BL/6 and DBA/2). The resulting strain distribution pattern showed high concordance with a marker that mapped to chromosome 18 (19 cM). Linkage with this genomic interval was associated with a likelihood of odds score of 3.3, surpassing the level required for significance. Interestingly, this segment, containing the EGR-1 gene, shows synteny with human chromosome 5q, a region strongly associated with various hematological malignancies. Our findings indicate that a gene mapping to this region is mutated in either C57BL/6 or DBA/2 (and possibly AKR) mice. These studies in apparently healthy mice may facilitate the identification of a gene implicated in human 5q-syndromes.

[Clonal hematopoiesis: a risk factor for leukemia and cardiovascular disease?] / Klonale hematopoëse.

Upon ageing, hematopoietic stem or progenitor cells harboring acquired leukemia-associated mutations may expand clonally and become detectable in peripheral blood. So-called clonal hematopoiesis may be detected in 5-55% of (otherwise healthy) individuals aged ≥ 70 years. Clonal hematopoiesis is associated with a higher risk of developing hematological neoplasms, although most individuals never develop malignant disease. Surprisingly, clonal hematopoiesis is also recognized as a new cardiovascular risk factor. Specific patient categories may be at higher risk for the consequences of clonal hematopoiesis. For future risk stratification, there is a need to distinguish high-risk clonal hematopoiesis from 'physiological' ageing processes. In this article we summarize current knowledge on clonal hematopoiesis and its clinical implications. Given the widespread application of next-generation sequencing in routine diagnostics, multidisciplinary recommendations for clinical management of individuals with detected clonal hematopoiesis should be developed.

Independent outdoor mobility of persons with multiple sclerosis - A systematic review.

BACKGROUND: Multiple sclerosis (MS) can manifest itself in many ways, all of which can affect the independent outdoor mobility of persons with MS (pwMS). In most studies, mobility of pwMS is defined by the ability to walk. However, mobility comprises more than walking alone. This systematic review provides an overview of the literature on several types of independent outdoor mobility of pwMS. We aimed to identify which specific factors may influence outdoor mobility and how the lives of pwMS may be affected by a reduced mobility. METHODS: A systematic literature search was performed, using three databases (PubMed, PsychInfo and Web of Science). Studies had to describe a group of pwMS sclerosis and had to concern some type of mobility other than walking. RESULTS: The 57 studies that fulfilled the criteria included in total 10,394 pwMS and in addition, 95,300 pwMS in separate prevalence study. These studies showed that pwMS as a group have a decreased fitness to drive, make use of a wheelchair or mobility scooter more often and have difficulties making use of public transport. Mobility problems especially occur in patients with cognitive problems, secondary progressive MS or high disability scores. CONCLUSIONS: The reduced mobility may prevent pwMS participating in society. However, few studies investigating interventions or rehabilitation options to improve mobility were found in the existing literature, highlighting an until now under recognised unmet need.

Posture effects on the calibratability of remote pulse oximetry in visible light.

OBJECTIVE: Remote pulse oximetry in visible light (VIS) is a relevant application of photoplethysmography (PPG). However, wavelengths penetrate at different depths and VIS-based pulse oximetry may not guarantee robustness to physiological variations of the skin properties. This paper shows how a simple manoeuver like a posture change can hamper the accuracy of a method relying on red and the less penetrating green wavelengths. APPROACH: Stationary subjects were measured under normoxic conditions while sitting and in the supine position. For each recording, we extracted remote PPG signals from forehead video recordings of 31 healthy adults at the red and green camera channels. The resulting normalized PPG-amplitudes, and its ratio, red-over-green (RoG), were compared between postures. The observed RoG changes were translated into estimates for arterial blood oxygen saturation (SpO2, %) errors by means of Monte Carlo simulations of the skin tissue. Simulations were also used to compare the calibratability errors of SpO2 in VIS against the conventional red-IR wavelengths. MAIN RESULTS: RoG differs significantly between postures (RoG: sitting, 0.100 [Formula: see text] 0.025; supine, 0.123 [Formula: see text] 0.033), mediated by PPG-amplitude changes in green. The posture interference in RoG may be mitigated by an offset correction. Without this correction, we estimated that the observed change in RoG causes SpO2 errors >[Formula: see text]. Analogous simulations involving red-IR wavelengths indicate SpO2 errors <[Formula: see text]. SIGNIFICANCE: Our results show that the calibrations for remote pulse oximetry in VIS require the specification of a fixed measurement position. Future work could be aimed at controlling for posture in measurements.

Mobilized peripheral blood stem cells provide rapid reconstitution but impaired long-term engraftment in a mouse model.

In this study, we use competitive repopulation to compare the quality and frequency of stem cells isolated from mobilized blood with stem cells isolated from bone marrow (BM) in a mouse model. Lin(-)Sca-1(+)c-Kit(+) (LSK) cells were harvested from control BM and peripheral blood of mice following granulocyte colony-stimulating factor (G-CSF) administration. LSK cells were used because of their resemblance to human CD34(+) cells. We confirmed that transplantation of phenotypically defined mobilized peripheral blood (MPB) stem cells results in rapid recovery of blood counts. However, in vitro results indicated that LSK cells purified from MPB had lower cobblestone area-forming cell day 35 activity compared to BM. Additionally, evaluation of chimerism after co-transplantation of LSK cells purified from blood and BM revealed that MPB stem cells contained 25-fold less repopulation potential compared to BM stem cells. Competitive repopulating unit frequency analysis showed that freshly isolated MPB LSK cells have 8.8-fold fewer cells with long-term repopulating ability compared to BM LSK cells. Secondary transplantation showed no further decline in contribution of hematopoiesis relative to BM. We conclude that the reduced frequency of stem cells within the LSK population of MPB, rather than poorer quality, causes the reduced repopulation potential.Bone Marrow Transplantation (2007) 39, 401-409. doi:10.1038/sj.bmt.1705601; published online 12 February 2007.

A history of loss of consciousness or post-traumatic amnesia in minor head injury: "conditio sine qua non" or one of the risk factors?

OBJECTIVE: A history of loss of consciousness (LOC) or post-traumatic amnesia (PTA) is commonly considered a prerequisite for minor head injury (MHI), although neurocranial complications also occur when LOC/PTA are absent, particularly in the presence of other risk factors. The purpose of this study was to evaluate whether known risk factors for complications after MHI in the absence of LOC/PTA have the same predictive value as when LOC/PTA are present. METHODS: A prospective multicentre study was performed in four university hospitals between February 2002 and August 2004 of consecutive blunt head injury patients (> or = 16 years) presenting with a normal level of consciousness and a risk factor. Outcome measures were any neurocranial traumatic CT finding and neurosurgical intervention. Common odds ratios (OR) were estimated for each of the risk factors and tested for homogeneity. RESULTS: 2462 patients were included: 1708 with and 754 without LOC/PTA. Neurocranial traumatic findings on CT were present in 7.5% and were more common when LOC/PTA was present (8.7%). Neurosurgical intervention was required in 0.4%, irrespective of the presence of LOC/PTA. ORs were comparable across the two subgroups (p>0.05), except for clinical evidence of a skull fracture, with high ORs both when LOC/PTA was present (OR = 37, 95% CI 17 to 80) or absent (OR = 6.9, 95% CI 1.8 to 27). LOC and PTA had significant ORs of 1.9 (95% CI 1.0 to 2.7) and 1.7 (95% CI 1.3 to 2.3), respectively. CONCLUSION: Known risk factors have comparable ORs in MHI patients with or without LOC or PTA. MHI patients without LOC or PTA need to be explicitly considered in clinical guidelines.