Handheld vital microscopy for the identification of microcirculatory alterations in cervical intraepithelial neoplasia and cervical cancer.

BACKGROUND: Ninety percent of cervical cancer (CC) diagnoses and deaths occur in low and middle-income countries (LMICs). Especially in these countries, where human and material resources are limited, there is a need for real-time screening methods that enable immediate treatment decisions (i.e., 'see and treat'). OBJECTIVE: To evaluate whether handheld vital microscopy (HVM) enables real-time detection of microvascular alterations associated with cervical intraepithelial neoplasia (CIN) and CC. METHODS: A cross-sectional study was conducted in an oncologic hospital and outpatient clinic, and included ten healthy controls, ten women with CIN, and ten women with CC. The microvasculature was assessed in four quadrants of the uterine cervix using HVM. The primary outcome was the presence of abnormal angioarchitecture (AA). Secondary outcomes included capillary loop density (CD), total vessel density (TVD), functional capillary density (FCD), and the proportion of perfused vessels (PPV). RESULTS: 198 image sequences of the cervical microvasculature were recorded. Compared to healthy controls, significantly more abnormal image sequences were observed in women with high-grade CIN (11 % vs. 44 %, P < 0.001) and women with CC (11 % vs. 69 %, P < 0.001). TVD, FCD, and PPV were lower in women with CIN and CC. CONCLUSIONS: HVM enables easy, real-time, non-invasive assessment of cervical lesions through the detection of microvascular alterations. Thereby, HVM potentially provides an opportunity for point-of-care screening, which may enable immediate treatment decisions (see and treat) and reduce the number of unnecessary surgical interventions.

Embedded macrophages induce intravascular coagulation in 3D blood vessel-on-chip.

Macrophages are innate immune cells that prevent infections and help in wound healing and vascular inflammation. While these cells are natural helper cells, they also contribute to chronic diseases, e.g., by infiltrating the endothelial layer in early atherosclerosis and by promoting vascular inflammation. There is a crosstalk between inflammatory pathways and key players in thrombosis, such as platelets and endothelial cells - a phenomenon known as 'thromboinflammation'. The role of the embedded macrophages in thromboinflammation in the context of vascular disease is incompletely understood. Blood vessels-on-chips, which are microfluidic vascular cell culture models, have been used extensively to study aspects of vascular disease, like permeability, immune cell adhesion and thrombosis. Blood perfusion assays in blood vessel-on-chip models benefit from multiple unique aspects of the models, such as control of microvessel structure and well-defined flow patterns, as well as the ability to perform live imaging. However, due to their simplified nature, blood vessels-on-chip models have not yet been used to capture the complex cellular crosstalk that is important in thromboinflammation. Using induced pluripotent stem cell-derived endothelial cells and polarized THP-1 monocytes, we have developed and systematically set up a 3D blood vessel-on-chip with embedded (lipid-laden) macrophages, which is created using sequential cell seeding in viscous finger patterned collagen hydrogels. We have set up a human whole blood perfusion assay for these 3D blood vessels-on-chip. An increased deposition of fibrin in the blood vessel-on-chip models containing lipid-laden macrophages was observed. We anticipate the future use of this advanced vascular in vitro model in drug development for early atherosclerosis or aspects of other vascular diseases.

Cost-utility analysis of a structured medication review compared to usual care in Parkinson's disease.

PURPOSE: For controlling symptoms in Parkinson's disease (PD) together with treating additional comorbidities, patients often face complex medication regimens, with suboptimal adherence, drug-related problems, and diminished therapy efficacy as a common consequence. A medication review could potentially tackle these issues, among others by optimizing drug treatment. Even if no change in clinical outcomes is observed, this intervention might decrease health care costs by reducing drug-related problems and hospital admissions. This study aimed to gain more insight in the health benefits and costs of a structured medication review (SMR) in PD. METHODS: A cost-utility analysis was performed, based on a multicenter randomized controlled trial with 202 PD patients with polypharmacy. The intervention group received an SMR, whereas the control group received usual care. The intervention effect after 6 months of follow-up was presented as incremental quality-adjusted life years (QALY) using the EQ-5D-5L questionnaire. Costs were based on real-world data. Missing data was imputed using multiple imputation techniques. Bootstrapping was used to estimate the uncertainty in all health and economic outcomes. RESULTS: The QALY gain in the intervention group compared to the control group was - 0.011 (95% CI - 0.043; 0.020). Incremental costs were €433 (95% CI - 873; 1687). When adapting a willingness-to-pay threshold of €20,000/QALY and €80,000/QALY, the probability of SMRs being cost-effective was 18% and 30%, respectively. CONCLUSION: A community pharmacist-led SMR in PD patients in the current setting shows no apparent benefit and is not cost-effective after 6 months, compared to usual care. TRIAL REGISTRATION: Netherlands Trial Register, NL4360. Registered 17 March 2014.

Protocol for a randomized controlled multicenter trial assessing the efficacy of leuprorelin for severe polycystic liver disease: the AGAINST-PLD study.

BACKGROUND: In patients with severe polycystic liver disease (PLD), there is a need for new treatments. Estrogens and possibly other female sex hormones stimulate growth in PLD. In some patients, liver volume decreases after menopause. Female sex hormones could therefore be a target for therapy. The AGAINST-PLD study will examine the efficacy of the GnRH agonist leuprorelin, which blocks the production of estrogen and other sex hormones, to reduce liver growth in PLD. METHODS: The AGAINST-PLD study is an investigator-driven, multicenter, randomized controlled trial. Institutional review board (IRB) approval was received at the University Medical Center of Groningen and will be collected in other sites before opening these sites. Thirty-six female, pre-menopausal patients, with a very large liver volume for age (upper 10% of the PLD population) and ongoing liver growth despite current treatment options will be randomized to direct start of leuprorelin or to 18 months standard of care and delayed start of leuprorelin. Leuprorelin is given as 3.75 mg subcutaneously (s.c.) monthly for the first 3 months followed by 3-monthly depots of 11.25 mg s.c. The trial duration is 36 months. MRI scans to measure liver volume will be performed at screening, 6 months, 18 months, 24 months and 36 months. In addition, blood will be drawn, DEXA-scans will be performed and questionnaires will be collected. This design enables comparison between patients on study treatment and standard of care (first 18 months) and within patients before and during treatment (whole trial). Main outcome is annualized liver growth rate compared between standard of care and study treatment. Secondary outcomes are PLD disease severity, change in liver growth within individuals and (serious) adverse events. The study is designed as a prospective open-label study with blinded endpoint assessment (PROBE). DISCUSSION: In this trial, we combined the expertise of hepatologist, nephrologists and gynecologists to study the effect of leuprorelin on liver growth in PLD. In this way, we hope to stop liver growth, reduce symptoms and reduce the need for liver transplantation in severe PLD. Trial registration Eudra CT number 2020-005949-16, registered at 15 Dec 2020. https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-005949-16 .

Peripartum fetal distress in diabetic women: a retrospective case-cohort study.

BACKGROUND: Major concerns of pregnancies complicated by diabetes mellitus are an increased risk of adverse perinatal outcome. The objective of this study was to analyse the rate of fetal distress during labor in women with type 1, type 2 and gestational diabetes compared to control women. METHODS: A retrospective case-cohort study was conducted at the VU University Medical Center, Amsterdam; a tertiary care hospital. 117 women with type 1 diabetes, 59 women with type 2 diabetes, 303 women with gestational diabetes and 15,260 control women were included, who delivered between March 2004 and February 2014. Linear and logistic regression analyses were used to compare maternal and pregnancy characteristics. Risk of fetal distress and perinatal asphyxia was assessed by multiple regression analyses, adjusted for confounding factors as age, smoking, parity, previous cesarean section, hypertensive disorder, pre-eclampsia, prematurity, induction of labor and macrosomia. Main outcome measure was fetal distress, defined either as clinical indication for instrumental or cesarean delivery; or low umbilical artery pH (UA pH), or admission to neonatal unit (NU). RESULTS: The indication for instrumental or cesarean delivery in women with type 1 and type 2 diabetes mellitus was more frequently based on fetal distress as compared to controls (adjusted OR 2.76 CI 1.74-4.40 and adjusted OR 2.31 CI 1.19-4.51, respectively). In comparison with the control group, infants of women with type 1 diabetes had an increased risk of UA pH < 7.20 (adjusted OR 1.88 CI 1.23-2.87) or UA pH < 7.10 (adjusted OR 3.35 CI 1.79-6.27). Also, infants of women with type 1 diabetes were at increased risk for admission to NU as compared to infants of control women (OR 8.07 CI 4.75-13.70). CONCLUSIONS: Women with type 1 and type 2 diabetes are at increased risk of fetal distress during labor as compared to controls.

Dual hypothermic oxygenated machine perfusion in liver transplants donated after circulatory death.

BACKGROUND: Experimental studies have suggested that end-ischaemic dual hypothermic oxygenated machine perfusion (DHOPE) may restore hepatocellular energy status and reduce reperfusion injury in donation after circulatory death (DCD) liver grafts. The aim of this prospective case-control study was to assess the safety and feasibility of DHOPE in DCD liver transplantation. METHODS: In consecutive DCD liver transplantations, liver grafts were treated with end-ischaemic DHOPE. Outcome was compared with that in a control group of DCD liver transplantations without DHOPE, matched for donor age, donor warm ischaemia time, and recipient Model for End-stage Liver Disease (MELD) score. All patients were followed for 1 year. RESULTS: Ten transplantations involving liver grafts treated with DHOPE were compared with 20 control procedures. There were no technical problems. All 6-month and 1-year graft and patient survival rates were 100 per cent in the DHOPE group. Six-month graft survival and 1-year graft and patient survival rates in the control group were 80, 67 and 85 per cent respectively. During DHOPE, median (i.q.r.) hepatic adenosine 5'-triphosphate (ATP) content increased 11-fold, from 6 (3-10) to 66 (42-87) µmol per g protein (P = 0·005). All DHOPE-preserved livers showed excellent early function. At 1 week after transplantation peak serum alanine aminotransferase (ALT) and bilirubin levels were twofold lower in the DHOPE group than in the control group (ALT: median 966 versus 1858 units/l respectively, P = 0·006; bilirubin: median 1·0 (i.q.r. 0·7-1·4) versus 2·6 (0·9-5·1) mg/dl, P = 0·044). None of the ten DHOPE-preserved livers required retransplantation for non-anastomotic biliary stricture, compared with five of 20 in the control group (P = 0·140). CONCLUSION: This clinical study of end-ischaemic DHOPE in DCD liver transplantation suggests that the technique restores hepatic ATP, reduces reperfusion injury, and is safe and feasible. RCTs with larger numbers of patients are warranted to assess the efficacy in reducing post-transplant biliary complications.

An insight into the antibiofilm properties of Costa Rican stingless bee honeys.

OBJECTIVE: There is an increasing search for antibiofilm agents that either have specific activity against biofilms or may act in synergy with antimicrobials. Our objective is to examine the the antibiofilm properties of stingless bee honeys. METHOD: Meliponini honeys from Costa Rica were examined along with Medihoney as a reference. All honeys were submitted to a screening composed of minimum inhibitory concentration, inhibition of biofilm formation and biofilm destruction microplate-based assays against a Staphylococcus aureus biofilm forming strain. Dialysis led to the isolation of an antibiofilm fraction in Tetragonisca angustula honeys. The honey antibiofilm fraction was evaluated for protease activity and for any synergistic effect with antibiotics on a Staphylococcus aureus biofilm. The active fraction was then separated through activity guided isolation techniques involving SDS-PAGEs, anion exchange and size exclusion fast protein liquid chromatographies. The fractions obtained and the isolated antibiofilm constituents were tested for amylase and DNase activity. RESULTS: A total of 57 Meliponini honeys from Costa Rica were studied in this research. The honeys studied belonged to the Tetragonisca angustula (n=36) and Melipona beecheii (n=21) species. Costa Rican Tetragonisca angustula honeys can inhibit the planktonic growth, biofilm formation, and are capable of destroying a Staphylococcus aureus biofilm. The antibiofilm effect was observed in the protein fraction of Tetragonisca angustula honeys. The biofilm destruction proteins allowed ampicillin and vancomycin to recover their antimicrobial activity over a Staphylococcus aureus biofilm. The antibiofilm proteins are of bee origin, and their activity was not due to serine, cysteine or metalloproteases. There were 2 proteins causing the antibiofilm action; these were named the Tetragonisca angustula biofilm destruction factors (TABDFs). TABDF-1 is a monomeric protein of approximately 50kDa that is responsible of the amylase activity of Tetragonisca angustula honeys. TABDF-2 is a protein monomer of approximately 75kDa. CONCLUSION: Tetragonisca angustula honeys from Costa Rica are a promising candidate for research and development of novel wound dressings focused on the treatment of acute and chronic Staphylococcus aureus biofilm wound infections.

CD58 mutations are common in Hodgkin lymphoma cell lines and loss of CD58 expression in tumor cells occurs in Hodgkin lymphoma patients who relapse.

CD58 is involved in immune recognition of tumor cells via binding of the CD2 receptor expressed on cytotoxic T cells. In diffuse large B-cell lymphoma, mutations of the CD58 gene are reported to contribute to immune evasion of the tumor cells. We previously showed CD58 mutations in three Hodgkin lymphoma (HL) cell lines by whole-exome sequencing. In this study, we confirmed the mutations by Sanger sequencing at the DNA and RNA level and showed low levels or total loss of CD58 mRNA expression in two of the three cell lines. CD58 protein expression as determined by flow cytometry, western blotting and immunohistochemistry was absent in all three mutated HL cell lines. In primary tissue samples, loss of CD58 expression was observed in 11% of the patients who relapse. These data suggest that loss of CD58 is a potential immune escape mechanism of HL tumor cells, especially in clinically aggressive disease.

Comprehensive analysis of miRNA expression in T-cell subsets of rheumatoid arthritis patients reveals defined signatures of naive and memory Tregs.

Disturbed expression of microRNAs (miRNAs) in regulatory T cells (Tregs) leads to development of autoimmunity in experimental mouse models. However, the miRNA expression signature characterizing Tregs of autoimmune diseases, such as rheumatoid arthritis (RA) has not been determined yet. In this study, we have used a microarray approach to comprehensively analyze miRNA expression signatures of both naive Tregs (CD4+CD45RO-CD25++) and memory Tregs (CD4+CD45RO+CD25+++), as well as conventional naive (CD4+CD45RO-CD25-) and memory (CD4+CD45RO+CD25-) T cells (Tconvs) derived from peripheral blood of RA patients and matched healthy controls. Differential expression of selected miRNAs was validated by TaqMan-based quantitative reverse transcription-PCR. We found a positive correlation between increased expression of miR-451 in T cells of RA patients and disease activity score (DAS28), erythrocyte sedimentation rate levels and serum levels of interleukin-6. Moreover, we found characteristic, disease- and treatment-independent, global miRNA expression signatures defining naive Tregs, memory Tregs, naive Tconvs and memory Tconvs. The analysis allowed us to define miRNAs characteristic for a general naive phenotype (for example, miR-92a) and a general memory phenotype (for example, miR-21, miR-155). Importantly, the analysis allowed us to define miRNAs that are specifically expressed in both naive and memory Tregs, defining as such miRNA signature characterizing the Treg phenotype (that is, miR-146a, miR-3162, miR-1202, miR-1246 and miR-4281).

BBB on chip: microfluidic platform to mechanically and biochemically modulate blood-brain barrier function.

The blood-brain barrier (BBB) is a unique feature of the human body, preserving brain homeostasis and preventing toxic substances to enter the brain. However, in various neurodegenerative diseases, the function of the BBB is disturbed. Mechanisms of the breakdown of the BBB are incompletely understood and therefore a realistic model of the BBB is essential. We present here the smallest model of the BBB yet, using a microfluidic chip, and the immortalized human brain endothelial cell line hCMEC/D3. Barrier function is modulated both mechanically, by exposure to fluid shear stress, and biochemically, by stimulation with tumor necrosis factor alpha (TNF-α), in one single device. The device has integrated electrodes to analyze barrier tightness by measuring the transendothelial electrical resistance (TEER). We demonstrate that hCMEC/D3 cells could be cultured in the microfluidic device up to 7 days, and that these cultures showed comparable TEER values with the well-established Transwell assay, with an average (± SEM) of 36.9 Ω.cm(2) (± 0.9 Ω.cm(2)) and 28.2 Ω.cm(2) (± 1.3 Ω.cm(2)) respectively. Moreover, hCMEC/D3 cells on chip expressed the tight junction protein Zonula Occludens-1 (ZO-1) at day 4. Furthermore, shear stress positively influenced barrier tightness and increased TEER values with a factor 3, up to 120 Ω.cm(2). Subsequent addition of TNF-α decreased the TEER with a factor of 10, down to 12 Ω.cm(2). This realistic microfluidic platform of the BBB is very well suited to study barrier function in detail and evaluate drug passage to finally gain more insight into the treatment of neurodegenerative diseases.

In situ spatiotemporal characterization and analysis of chemical reactions using an ATR-integrated microfluidic reactor.

Determining kinetic reaction parameters with great detail has been of utmost importance in the field of chemical reaction engineering. However, commonly used experimental and computational methods however are unable to provide sufficiently resolved spatiotemporal information that can aid in the process of understanding these chemical reactions. With our work, we demonstrate the use of a custom designed single-bounce ATR-integrated microfluidic reactor to obtain spatiotemporal resolution for in situ monitoring of chemical reactions. Having a single-bounce ATR accessory allows us to individually address different sensing areas, thereby providing the ability to obtain spatially and temporally resolved information. To further enhance the spatial resolution, we utilize the benefits of synchrotron IR radiation with the smallest beam spot-size ∼150 µm. An on-flow modular microreactor additionally allows us to monitor the chemical reaction in situ, where the temporal characterization can be controlled with the operational flowrate. With a unique combination of experimental measurements and numerical simulations, we characterize and analyse a model SN2 reaction. For a chemical reaction between benzyl bromide (BB) and sodium azide (SA) to produce benzyl azide (BA), we successfully show the capability of our device to determine the diffusion coefficients of BB and SA as 0.367 ± 0.115 10-9 m2 s-1 and 1.17 ± 0.723 10-9 m2 s-1, respectively. Finally, with the above characteristics of our device, we also calculate a reaction rate of k = 0.0005 (m3s-1mol-1) for the given chemical reaction.

The barriers and needs of transgender men in pregnancy and childbirth: A qualitative interview study.

OBJECTIVE: Transgender and gender diverse individuals are individuals whose gender identity differs from their sex assigned at birth. The discordance between gender identity and sex assignment may cause significant psychological distress: gender dysphoria. Transgender individuals may choose to undergo gender-affirming hormone treatment or surgery, but some decide to (temporarily) refrain from surgery and gender affirming hormone treatment and hence retain the possibility to become pregnant. Pregnancy may enhance feelings of gender dysphoria and isolation. To improve perinatal care for transgender individuals and their health care providers, we conducted interviews to explore the needs and barriers of transgender men in family planning, pregnancy, childbirth, puerperium and perinatal care. DESIGN: In this qualitative study five in-depth semi-structured interviews were conducted with Dutch transgender men who had given birth while identifying on the transmasculine spectrum. The interviews were conducted online through a video remote-conferencing software program (n=4) or live (n=1). Interviews were transcribed verbatim. An inductive approach was used to find patterns and collect data from the participants' narratives and constant comparative method was adapted in analysing the interviews. MEASUREMENTS AND FINDINGS: The experiences of transgender men regarding the preconception period, pregnancy and puerperium and with perinatal care varied widely. Though all participants expressed overall positive experiences, their narratives emphasized they had to overcome substantial hurdles pursuing pregnancy. For instance the necessity to prioritise becoming pregnant over gender transitioning, lack of support by healthcare providers and increased gender dysphoria and isolation during pregnancy KEY CONCLUSIONS: Since pregnancy in transgender men enhances feelings of gender dysphoria, transgender men comprise a vulnerable group in perinatal care. Health care providers are perceived as feeling unaccustomed for the care of transgender patients, as they are perceived to often lack the right tools and knowledge to provide adequate care. Our findings help strengthen the foundation of insight in the needs and hurdles of transgender men pursuing pregnancy and therefore may guide health care providers to provide equitable perinatal care, and emphasize the necessity of patient-centred gender-inclusive perinatal care. A guideline including the option for consultation of an expertise center is advised to facilitate patient-centered gender-inclusive perinatal care.

Circulating tumor cells in small-cell lung cancer: a predictive and prognostic factor.

BACKGROUND: Initial response of small-cell lung cancer (SCLC) to chemotherapy is high, and recurrences occur frequently, leading to early death. This study investigated the prognostic value of circulating tumor cells (CTCs) in patients with SCLC and whether changes in CTCs can predict response to chemotherapy. Patients and methods In this multicenter prospective study, blood samples for CTC analysis were obtained from 59 patients with SCLC before, after one cycle, and at the end of chemotherapy. CTCs were measured using CellSearch systems. RESULTS: At baseline, lower numbers of CTCs were observed for 21 patients with limited SCLC (median = 6, range 0-220) compared with 38 patients with extensive stage (median = 63, range 0-14,040). Lack of measurable CTCs (27% of patients) was associated with prolonged survival (HR 3.4; P ≤ 0.001). CTCs decreased after one cycle of chemotherapy; this decrease was not associated with tumor response after four cycles of chemotherapy. CTC count after the first cycle of chemotherapy was the strongest predictor for overall survival (HR 5.7; 95% CI 1.7-18.9; P = 0.004). CONCLUSION: Absolute CTCs after one cycle of chemotherapy in patients with SCLC is the strongest predictor for response on chemotherapy and survival. Patients with low initial CTC numbers lived longer than those with higher CTCs.

Improved conversion rates in drug screening applications using miniaturized electrochemical cells with frit channels.

This paper reports a novel design of a miniaturized three-electrode electrochemical cell, the purpose of which is aimed at generating drug metabolites with a high conversion efficiency. The working electrode and the counter electrode are placed in two separate channels to isolate the reaction products generated at both electrodes. The novel design includes connecting channels between these two electrode channels to provide a uniform distribution of the current density over the entire working electrode. In addition, the effect of ohmic drop is decreased. Moreover, two flow resistors are included to ensure an equal flow of analyte through both electrode channels. Total conversion of fast reacting ions is achieved at flow rates up to at least 8 µL/min, while the internal chip volume is only 175 nL. Using this electrochemical chip, the metabolism of mitoxantrone is studied by microchip electrospray ionization-mass spectrometry. At an oxidation potential of 700 mV, all known metabolites from direct oxidation are observed. The electrochemical chip performs equally well, compared to a commercially available cell, but at a 30-fold lower flow of reagents.

Transfer effects of training-induced visual field recovery in patients with chronic stroke.

OBJECTIVE: Visual training of light detection in the transition zone between blind and healthy hemianopic visual fields leads to improvement of color and simple pattern recognition. Recently, we demonstrated that visual field enlargement (VFE) also occurs when an area just beyond the transition zone is stimulated. In the current study, we attempted to determine whether this peripheral training also causes improvement in color and shape perception and reading speed. Further, we evaluated which measure of VFE relates best to improvements in performance: the average border shift (ABS) in degrees or the estimated amount of cortical surface gain (ECSG) in millimeters, using the cortical magnification factor (CMF). METHOD: Twelve patients received 40 sessions of 1-hour restorative function training (RFT). Before and after training, we measured visual fields and reading speed. Additionally, color and shape perception in the trained visual field area was measured in 7 patients. RESULTS: VFE was found for 9 of 12 patients. Significant improvements were observed in reading speed for 8 of 12 patients and in color and shape perception for 3 of 7 patients. ECSG correlates significantly with performance; ABS does not. Our data indicate that the threshold ECSG, needed for significant changes in color and shape perception and reading speed, is about 6 mm. CONCLUSIONS: White stimulus training-induced VFE can lead to improved color and shape perception and to increased reading speed in and beyond the pretraining transition zone if ECSG is sufficiently large. The latter depends on the eccentricity of the VFE.

Effects of vision restoration training on early visual cortex in patients with cerebral blindness investigated with functional magnetic resonance imaging.

Cerebral blindness is a loss of vision as a result of postchiasmatic damage to the visual pathways. Parts of the lost visual field can be restored through training. However, the neuronal mechanisms through which training effects occur are still unclear. We therefore assessed training-induced changes in brain function in eight patients with cerebral blindness. Visual fields were measured with perimetry and retinotopic maps were acquired with functional magnetic resonance imaging (fMRI) before and after vision restoration training. We assessed differences in hemodynamic responses between sessions that represented changes in amplitudes of neural responses and changes in receptive field locations and sizes. Perimetry results showed highly varied visual field recovery with shifts of the central visual field border ranging between 1 and 7°. fMRI results showed that, although retinotopic maps were mostly stable over sessions, there was a small shift of receptive field locations toward a higher eccentricity after training in addition to increases in receptive field sizes. In patients with bilateral brain activation, these effects were stronger in the affected than in the intact hemisphere. Changes in receptive field size and location could account for limited visual field recovery (± 1°), although it could not account for the large increases in visual field size that were observed in some patients. Furthermore, the retinotopic maps strongly matched perimetry measurements before training. These results are taken to indicate that local visual field enlargements are caused by receptive field changes in early visual cortex, whereas large-scale improvement cannot be explained by this mechanism.

Coherent Cherenkov radiation from cosmic-ray-induced air showers.

Very energetic cosmic rays entering the atmosphere of Earth will create a plasma cloud moving with almost the speed of light. The magnetic field of Earth induces an electric current in this cloud which is responsible for the emission of coherent electromagnetic radiation. We propose to search for a new effect: Because of the index of refraction of air, this radiation is collimated in a Cherenkov cone. To express the difference from usual Cherenkov radiation, i.e., the emission from a fast-moving electric charge, we call this magnetically induced Cherenkov radiation. We indicate its signature and possible experimental verification.