Nonequilibrium sensing of volatile compounds using active and passive analyte delivery.

Although sensor technologies have allowed us to outperform the human senses of sight, hearing, and touch, the development of artificial noses is significantly behind their biological counterparts. This largely stems from the sophistication of natural olfaction, which relies on both fluid dynamics within the nasal anatomy and the response patterns of hundreds to thousands of unique molecular-scale receptors. We designed a sensing approach to identify volatiles inspired by the fluid dynamics of the nose, allowing us to extract information from a single sensor (here, the reflectance spectra from a mesoporous one-dimensional photonic crystal) rather than relying on a large sensor array. By accentuating differences in the nonequilibrium mass-transport dynamics of vapors and training a machine learning algorithm on the sensor output, we clearly identified polar and nonpolar volatile compounds, determined the mixing ratios of binary mixtures, and accurately predicted the boiling point, flash point, vapor pressure, and viscosity of a number of volatile liquids, including several that had not been used for training the model. We further implemented a bioinspired active sniffing approach, in which the analyte delivery was performed in well-controlled 'inhale-exhale' sequences, enabling an additional modality of differentiation and reducing the duration of data collection and analysis to seconds. Our results outline a strategy to build accurate and rapid artificial noses for volatile compounds that can provide useful information such as the composition and physical properties of chemicals, and can be applied in a variety of fields, including disease diagnosis, hazardous waste management, and healthy building monitoring.

Diffusiophoretic Fast Swelling of Chemically Responsive Hydrogels.

Acid-induced release of stored ions from polyacrylic acid hydrogels (with a free surface fully permeable to the ion and acid) was observed to increase the gel osmotic pressure that leads to rapid swelling faster than the characteristic solvent absorption rate of the gel. The subsequent equilibration of the diffusing ion concentration across the gel surface diminishes the osmotic pressure. Then, the swollen gel contracts, thereby completing one actuation cycle. We develop a continuum poroelastic theory that explains the experiments by introducing a "gel diffusiophoresis" mechanism: Steric repulsion between the gel polymers and released ions can induce a diffusio-osmotic solvent intake counteracted by the diffusiophoretic expansion of the gel network that ceases when the ion gradient vanishes. For applications ranging from drug delivery to soft robotics, engineering the gel diffusiophoresis may enable stimuli-responsive hydrogels with amplified strain rates and power output.

A multiscale whole-cell theory for mechanosensitive migration on viscoelastic substrates.

Increasing experimental evidence validates that both the elastic stiffness and viscosity of the extracellular matrix regulate mesenchymal cell behavior, such as the rational switch between durotaxis (cell migration to stiffer regions), anti-durotaxis (migration to softer regions), and adurotaxis (stiffness-insensitive migration). To reveal the mechanisms underlying the crossover between these motility regimes, we have developed a multiscale chemomechanical whole-cell theory for mesenchymal migration. Our framework couples the subcellular focal adhesion dynamics at the cell-substrate interface with the cellular cytoskeletal mechanics and the chemical signaling pathways involving Rho GTPase proteins. Upon polarization by the Rho GTPase gradients, our simulated cell migrates by concerted peripheral protrusions and contractions, a hallmark of the mesenchymal mode. The resulting cell dynamics quantitatively reproduces the experimental migration speed as a function of the uniform substrate stiffness and explains the influence of viscosity on the migration efficiency. In the presence of stiffness gradients and absence of chemical polarization, our simulated cell can exhibit durotaxis, anti-durotaxis, and adurotaxis respectively with increasing substrate stiffness or viscosity. The cell moves toward an optimally stiff region from softer regions during durotaxis and from stiffer regions during anti-durotaxis. We show that cell polarization through steep Rho GTPase gradients can reverse the migration direction dictated by the mechanical cues. Overall, our theory demonstrates that opposing durotactic behaviors emerge via the interplay between intracellular signaling and cell-medium mechanical interactions in agreement with experiments, thereby elucidating complex mechanosensing at the single-cell level.

Achiral symmetry breaking and positive Gaussian modulus lead to scalloped colloidal membranes.

In the presence of a nonadsorbing polymer, monodisperse rod-like particles assemble into colloidal membranes, which are one-rod-length-thick liquid-like monolayers of aligned rods. Unlike 3D edgeless bilayer vesicles, colloidal monolayer membranes form open structures with an exposed edge, thus presenting an opportunity to study elasticity of fluid sheets. Membranes assembled from single-component chiral rods form flat disks with uniform edge twist. In comparison, membranes composed of a mixture of rods with opposite chiralities can have the edge twist of either handedness. In this limit, disk-shaped membranes become unstable, instead forming structures with scalloped edges, where two adjacent lobes with opposite handedness are separated by a cusp-shaped point defect. Such membranes adopt a 3D configuration, with cusp defects alternatively located above and below the membrane plane. In the achiral regime, the cusp defects have repulsive interactions, but away from this limit we measure effective long-ranged attractive binding. A phenomenological model shows that the increase in the edge energy of scalloped membranes is compensated by concomitant decrease in the deformation energy due to Gaussian curvature associated with scalloped edges, demonstrating that colloidal membranes have positive Gaussian modulus. A simple excluded volume argument predicts the sign and magnitude of the Gaussian curvature modulus that is in agreement with experimental measurements. Our results provide insight into how the interplay between membrane elasticity, geometrical frustration, and achiral symmetry breaking can be used to fold colloidal membranes into 3D shapes.

Colloidal membranes of hard rods: unified theory of free edge structure and twist walls.

Monodisperse suspensions of rod like chiral fd viruses are condensed into a rod-length thick colloidal monolayers of aligned rods by depletion forces. Twist deformations of the molecules are expelled to the monolayer edge as in a chiral smectic A liquid crystal, and a cholesteric band forms at the edge. Coalescence of two such isolated membranes results in a twist wall sandwiched between two regions of aligned rods, dubbed π-walls. By modeling the membrane as a binary fluid of coexisting cholesteric and chiral smectic A liquid-crystalline regions, we develop a unified theory of the π-walls and the monolayer edge. The mean-field analysis of our model yields the molecular tilt profiles, the local thickness change, and the crossover from smectic to cholesteric behavior at the monolayer edge and across the π-wall. Furthermore, we calculate the line tension associated with the formation of these interfaces. Our model offers insights regarding the stability and the detailed structure of the π-wall and the monolayer edge.

HPA-5 typing discrepancy reveals an Ile503Leu substitution in platelet GPIa (α2 integrin).

BACKGROUND AND OBJECTIVES: In fetal/neonatal thrombocytopenia, maternal alloimmunization is diagnosed by the identification of the maternal alloantibody and the offending paternal antigen inherited by the foetus/neonate. Today, for practical reasons, most laboratories perform platelet genotyping instead of phenotyping. Here, we report the case of a human platelet antigen (HPA)-5 genotype/phenotype discrepancy observed in a mother who delivered a mildly thrombocytopenic newborn. MATERIALS AND METHODS: Platelet antibody detection and platelet phenotyping were performed using the MAIPA assay; platelet genotypes were determined using BeadChip technology (BioArray), PCR-SSP, PCR-RFLP and sequencing. RESULTS: Serological investigations revealed the presence of maternal anti-GPIIbIIIa autoantibodies. No alloantibodies were detected. No feto-maternal platelet incompatibility was observed for HPA-1 to -21. The mother and newborn were genotyped as HPA-5aa using BeadChips, but as HPA-5a (weak b) with PCR-SSP and HPA-5ab with PCR-RFLP. Mother's platelets were phenotyped as HPA-5b(+). GPIa exon 13 sequencing confirmed the HPA-5ab genotype of the mother and newborn, and revealed an NM_002203.3:c.1594A>C mutation near the HPA-5 polymorphism (5' side), leading to an I503L amino acid change. CONCLUSION: Feto-maternal alloimmunization was ruled out: the neonatal thrombocytopenia probably resulted from maternal anti-GPIIbIIIa autoantibodies. This case highlights that platelet typing should be performed using two different methods to avoid false diagnosis.

Sensitivity of assays for the detection of HPA-1a antibodies: results of an international workshop demonstrating the impact of cation chelation from integrin αIIbß3 on three widely used assays.

BACKGROUND AND OBJECTIVES: HPA-1a antibodies account for 70-80% of cases of fetal-neonatal alloimmune thrombocytopenia (FNAIT) in Caucasians. However, numerous workshops have demonstrated variability in their detection. We recently showed that exposure of αIIbß3 to ethylene diamine tetraacetic acid (EDTA) affected binding of many anti-αIIbß3 monoclonal, and HPA-1a allo-, antibodies; this adversely affected sensitivity of the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay and indirect platelet immunofluorescence test (PIFT). This study presents results from an international workshop studying the impact of cation chelation on HPA-1a antibody detection in routine diagnostic laboratories. MATERIALS AND METHODS: Serum and EDTA-anticoagulated plasma samples containing anti-HPA-1a were distributed to 39 laboratories. Participants were asked to detect and identify any HPA antibodies present. RESULTS: 2/39 (5.1%) participants were able to detect and identify anti-HPA-1a in the serum, but not in the plasma sample. EDTA plasma reduced MAIPA assay sensitivity by ≥ 20% in 17/24 (70.8%) laboratories and by ≥ 50% in 9/24 (37.5%) when using HPA-1a1a platelets (mean: 27.7%, range 0-85.1%); when using HPA-1a1b platelets 3/4 (75%), participants reported ≥ 50% loss of sensitivity (mean 65.6%, range 0-96.6%). A small but significant increase in optical densities was observed in antigen capture ELISA assays when using plasma (mean difference: 0.081, P < 0.01). Insufficient PIFT data were returned to draw firm conclusions. CONCLUSION: Use of EDTA plasma significantly affects the sensitivity of the MAIPA assay and can affect detection of even potent, FNAIT-causing examples of anti-HPA-1a. These data highlight the importance of use of αIIbß3 in an appropriate conformation for the sensitive detection of anti-HPA-1a.

Structural issues affecting creation of a community action and advocacy board.

The most effective woman-initiated method to prevent HIV/sexually transmitted infections is the female condom (FC). Yet, FCs are often difficult to find and denigrated or ignored by community health and service providers. Evidence increasingly supports the need to develop and test theoretically driven, multilevel interventions using a community-empowerment framework to promote FCs in a sustained way. We conducted a study in a midsized northeastern US city (2009-2013) designed to create, mobilize and build capacity of a community group to develop and implement multilevel interventions to increase availability, accessibility and support for FCs in their city. The Community Action and Advocacy Board (CAAB) designed and piloted interventions concurrently targeting community, organizational and individual levels. Ethnographic observation of the CAAB training and intervention planning and pilot implementation sessions documented the process, preliminary successes, challenges and limitations of this model. The CAAB demonstrated ability to conceptualize, plan and initiate multilevel community change. However, challenges in group decision-making and limitations in members' availability or personal capacity constrained CAAB processes and intervention implementation. Lessons from this experience could inform similar efforts to mobilize, engage and build capacity of community coalitions to increase access to and support for FCs and other novel effective prevention options for at-risk women.

Cardiac syncope due to pain: report of a case responsive to duloxetine treatment.

Neurocardiogenic syncope comprises situations triggered by neurological reflexes resulting in abnormal responses of the neurocardiovascular system that cause loss of consciousness. A vast number of clinical conditions may cause this disorder including pain, defecation, micturition, swallowing, cough, sudden fear or excitement, exercise, and long-time standing. Treatment options for syncope prevention are not satisfactory. Several agents were used for pharmacological treatment without success. Selective inhibitors of neuronal norepinephrine transporter (NET) like duloxetine may play a role in neurally mediated syncope by increasing synaptic norepinephrine levels. Therefore, we report the effect of duloxetine in a patient with pain-induced syncope resistant to standard regimens.

Retinal degeneration characterizes a spinocerebellar ataxia mapping to chromosome 3p.

A heterogeneous group of neurological disorders known as the spinocerebellar ataxias (SCA) are characterized by degeneration of the cerebellum, spinal cord and brainstem. We describe linkage analysis in four unusual SCA families revealing a distinct disease locus on chromosome 3p14-21.1. The disease in these families is distinguished from other forms of SCA by concomitant retinal degeneration. Initial visual problems leading to blindness, disabling ataxia and anticipation are seen in all kindreds. The anticipation in these families suggests a dynamic mutation at this locus. Eventual molecular characterization of this disease may provide valuable insights into the processes of both neural and retinal degeneration.

A multiscale theory for spreading and migration of adhesion-reinforced mesenchymal cells.

We present a chemomechanical whole-cell theory for the spreading and migration dynamics of mesenchymal cells that can actively reinforce their adhesion to an underlying viscoelastic substrate as a function of its stiffness. Our multiscale model couples the adhesion reinforcement effect at the subcellular scale with the nonlinear mechanics of the nucleus-cytoskeletal network complex at the cellular scale to explain the concurrent monotonic area-stiffness and non-monotonic speed-stiffness relationships observed in experiments: we consider that large cell spreading on stiff substrates flattens the nucleus, increasing the viscous drag force on it. The resulting force balance dictates a reduction in the migration speed on stiff substrates. We also reproduce the experimental influence of the substrate viscosity on the cell spreading area and migration speed by elucidating how the viscosity may either maintain adhesion reinforcement or prevent it depending on the substrate stiffness. Additionally, our model captures the experimental directed migration behaviour of the adhesion-reinforced cells along a stiffness gradient, known as durotaxis, as well as up or down a viscosity gradient (viscotaxis or anti-viscotaxis), the cell moving towards an optimal viscosity in either case. Overall, our theory explains the intertwined mechanics of the cell spreading, migration speed and direction in the presence of the molecular adhesion reinforcement mechanism.

Colony-like Protocell Superstructures.

We report the formation, growth, and dynamics of model protocell superstructures on solid surfaces, resembling single cell colonies. These structures, consisting of several layers of lipidic compartments enveloped in a dome-shaped outer lipid bilayer, emerged as a result of spontaneous shape transformation of lipid agglomerates deposited on thin film aluminum surfaces. Collective protocell structures were observed to be mechanically more stable compared to isolated spherical compartments. We show that the model colonies encapsulate DNA and accommodate nonenzymatic, strand displacement DNA reactions. The membrane envelope is able to disassemble and expose individual daughter protocells, which can migrate and attach via nanotethers to distant surface locations, while maintaining their encapsulated contents. Some colonies feature "exocompartments", which spontaneously extend out of the enveloping bilayer, internalize DNA, and merge again with the superstructure. A continuum elastohydrodynamic theory that we developed suggests that a plausible driving force behind subcompartment formation is attractive van der Waals (vdW) interactions between the membrane and surface. The balance between membrane bending and vdW interactions yields a critical length scale of 236 nm, above which the membrane invaginations can form subcompartments. The findings support our hypotheses that in extension of the "lipid world hypothesis", protocells may have existed in the form of colonies, potentially benefiting from the increased mechanical stability provided by a superstructure.

Stakeholder Assessment of Evidence-Based Guideline Dissemination and Implementation in a Dental Group Practice.

OBJECTIVE: This evaluation captures the perspectives of multiple stakeholders within a salaried dental care delivery organization (dentists, dental assistants, dental hygienists, and dental management) on the implementation of a pit-and-fissure sealant guideline in the Kaiser Permanente Dental Program. Also assessed is the role of formal processes and structures in providing a framework for guideline implementation. METHODS: We collected qualitative data through field observations, stakeholder interviews (n = 6), and focus groups (30 participants in 5 focus groups). Field observation notes captured summaries of conversations and other activities. Interviews and focus groups were recorded and transcribed. We analyzed transcripts and field notes using a template analysis with NVivo 12 software to identify themes related to the existing implementation process of clinical guidelines and stakeholder perspectives on the strengths and weaknesses of this process. RESULTS: Stakeholders perceived 2 main barriers for achieving implementation of the pit-and-fissure sealant guideline: 1) shortcomings in the implementation infrastructure resulting in lack of clarity about the roles and responsibilities in the guideline implementation process and lack of effective mechanisms to disseminate guideline content and 2) resource constraints, such as limited human, space, and material resources. Perceived opportunities for the dissemination and implementation of guidelines included recognition of the importance of guidelines in dental practice and well-functioning workflows within dental specialties. CONCLUSION: Our research points to the importance of developing and maintaining an infrastructure to ensure standardized, predictable mechanisms for implementation of guidelines and thereby promoting practice change. While addressing resource constraints may not be possible in all circumstances, an important step for improving guideline implementation-wherever feasible-would be the development of a robust implementation infrastructure that captures and delineates roles and responsibilities of different clinical actors in the guideline implementation process. KNOWLEDGE TRANSFER STATEMENT: The results of this study can be used by health care leadership and administrators to understand possible reasons for a lack of guideline implementation and provide suggestions for establishing sustainable infrastructure to promote the adoption of clinical guidelines in salaried dental clinics.

Human platelet antigen allele frequencies in different Algerian populations.

The frequencies of human platelet antigens (HPAs) vary between different populations and are a major determinant for the prevalence of HPA alloimmunization and its clinically associated entities. No report on HPA prevalence has previously been published for the Algerian populations which are ethnically diverse. The aim of this study was to determine the HPA allele frequencies in Algerian populations and to identify situations of incompatibility possibly leading to alloimmunization. A total of 485 healthy volunteer Algerian blood donors from different regions and representing different ethnic groups were included. HPA genotyping was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and/or polymerase chain reaction-sequence specific primer (PCR-SSP). The HPA-1 allele frequencies were close to the frequencies found in Caucasian populations. The presence of the molecule human leukocyte antigen (HLA)-DRB3*0101 (17.9%) increases the risk of alloimmunization. We observed an increase in the frequency of homozygous HPA-5b, particularly in the population of Annaba (7.61%) and the Mzab population (5.13%). The allele frequency HPA-2b (0.193-0.147) was similar to that seen in Sub-Saharan African populations. The high frequency of homozygotic HPA-2b (Kabyle 5%; Mzab 2.44% and Annaba 2.19%) could increase the risk of alloimmunization. GPIIb A(k) mutation (2614C>A) was found in these populations. This study is the first to report on HPA allele frequencies in Algerian populations. High allele frequencies were observed for HPA-1b (0.209-0.112), HPA-3b (0.411-0.312) and HPA-5b (0.217-0.087), leading to a high risk of alloimmunization in this population, especially the Mzab and the population of Annaba. Our results could have some impact in the diagnosis, prevention and treatment of alloimmune thrombocytopenia.

Report on the 14th International Society of Blood Transfusion Platelet Immunology Workshop.

BACKGROUND AND OBJECTIVES: The aims of the 14th ISBT Platelet Immunology Workshop were to evaluate in-house methods for detection of antibodies to human platelet antigens, to compare the sensitivity and specificity of antibody detection using a panel of monoclonal antibodies and to evaluate genotyping methods and establish procedures for drug-dependent antibody detection. MATERIALS AND METHODS: Forty-two laboratories from 23 countries participated. Samples and reagents provided for the five different exercises. RESULTS: The ability of participating laboratories to correctly identify the HPA antibody specificity in the nine samples ranged from 20% to 97%. The greatest difficulty was observed with samples that contained antibodies against HPA-3b and GPIV. The significant differences in optical density values by monoclonal antibody of immobilization of platelet antigens (MAIPA) assay were observed when testing the same platelet-specific antibodies. HPA genotyping of DNA with novel mutations did not significantly affect the results. The overall average discrepancy rate was 2·15% for genotyping of 10 DNA samples from well-characterized Epstein­Barr virus transformed cell lines. For detection of drug-dependent antibodies, excellent results for specificity and sensitivity were obtained by the laboratories using the MAIPA and flow cytometry. CONCLUSIONS: Most laboratories were able to identify the majority of HPA antibodies; however, significant disparities were observed in proficiency testing. MAIPA assay sensitivity is influenced by the monoclonal antibody clone used. DNA with new mutations and EBV cell lines are valuable samples to ensure accurate genotyping. A sensitive and specific drug-dependent antibody assay performed well in the hands of participants.

Fluoroquinolones in the management of community-acquired pneumonia.

AIMS: Review of the current guidelines for the use of respiratory fluoroquinolones in the management of community-acquired pneumonia (CAP). METHODS: Data were collected from recent clinical trials on fluoroquinolone therapy in patients with CAP and from updated recommendations of antimicrobial therapy in managing CAP, with a focus on current North American guidelines. RESULTS: Randomised clinical trials of respiratory fluoroquinolones (moxifloxacin, levofloxacin and gemifloxacin) in the treatment of CAP were identified and analysed. The bacteriology of CAP, and susceptibility rates, resistance rates and pharmacokinetic and pharmacodynamic properties of fluoroquinolones against causative pathogens in CAP, and adverse event profiles of these agents were described. Respiratory fluoroquinolones have broad-spectrum antibacterial activities against common causative pathogens in CAP and provide an important treatment option as monotherapy for outpatients with comorbidities and inpatients who are not admitted to the intensive care unit (ICU), including those with risk factors of drug-resistant Streptococcus pneumoniae. For treatment of ICU patients with severe CAP, it is recommended that fluoroquinolones be used in combination with a beta-lactam. Recent studies also demonstrated a more rapid resolution of clinical symptoms with the use of highly potent respiratory fluoroquinolones. DISCUSSION: Appropriate use of fluoroquinolone agents may shorten the duration of antimicrobial therapy and the length of hospital stay and contribute to the decreased development of resistance in patients with CAP. Adverse event profiles of these agents should be considered to facilitate the selection of an appropriate fluoroquinolone for appropriate CAP patients. CONCLUSION: The fluoroquinolone class, specifically those with adequate activity against respiratory pathogens, represents an important and convenient treatment option for patients with CAP.

Non-equilibrium signal integration in hydrogels.

Materials that perform complex chemical signal processing are ubiquitous in living systems. Their synthetic analogs would transform developments in biomedicine, catalysis, and many other areas. By drawing inspiration from biological signaling dynamics, we show how simple hydrogels have a previously untapped capacity for non-equilibrium chemical signal processing and integration. Using a common polyacrylic acid hydrogel, with divalent cations and acid as representative stimuli, we demonstrate the emergence of non-monotonic osmosis-driven spikes and waves of expansion/contraction, as well as traveling color waves. These distinct responses emerge from different combinations of rates and sequences of arriving stimuli. A non-equilibrium continuum theory we developed quantitatively captures the non-monotonic osmosis-driven deformation waves and determines the onset of their emergence in terms of the input parameters. These results suggest that simple hydrogels, already built into numerous systems, have a much larger sensing space than currently employed.

An International Reference Reagent (minimum sensitivity) for the detection of anti-human platelet antigen 1a.

BACKGROUND AND OBJECTIVES: The platelet-specific alloantibody anti-human platelet antigen (HPA) 1a is involved in feto-maternal alloimmune thrombocytopenia, post-transfusion purpura and platelet refractoriness. The existing minimum potency preparation for the detection of anti-HPA-1a (NIBSC code 93/710) was established by World Health Organization in 1997 and is used by laboratories to validate new assays or to calibrate 'in-house' controls. However, it has been well-used and a replacement is required. This report describes the production and comparative evaluation of a freeze-dried preparation of pooled human plasma, coded 05/106, containing anti-HPA-1a. MATERIALS AND METHODS: Plasma containing anti-HPA-1a was obtained and 2974 1-ml aliquots were prepared and freeze-dried in glass ampoules. In order to characterize the material and compare it to the existing reference material, three collaborative studies were organized, involving a total of 50 different laboratories in 23 countries. RESULTS: As expected only anti-HPA-1a could be detected in the plasma and no additional HPA or human leucocyte antigen antibodies were detected. When tested in titration, there was a wide variation in the sensitivity of antibody detection by different laboratories, irrespective of the technique used. However, there was no significant difference between the two materials when compared using a t-test. CONCLUSIONS: When diluted 1 in 2, most laboratories were able to detect the presence of anti-HPA-1a in both materials and the participants agreed that this was an appropriate level to set as the minimum sensitivity required. In October 2007, the World Health Organization Expert Committee on Biological Standardization approved the material 05/106 as an International Reference Reagent.

Infinitely robust order and local order-parameter tulips in Apollonian networks with quenched disorder.

For a variety of quenched random spin systems on an Apollonian network, including ferromagnetic and antiferromagnetic bond percolation and the Ising spin glass, we find the persistence of ordered phases up to infinite temperature over the entire range of disorder. We develop a renormalization-group technique that yields highly detailed information, including the exact distributions of local magnetizations and local spin-glass order parameters, which turn out to exhibit, as function of temperature, complex and distinctive tulip patterns.

[Fetal and neonatal alloimmune thrombocytopenias]. / Les thrombopénies foetales et néonatales allo-immunes.

Fetal and neonatal alloimmune thrombocytopenias result from maternal immunization against fetal specific platelet antigens inherited from the father that the mother lacks. The incidence has been estimated to one in 800 to one in 1000 live births. The most feared complication in case of severe thrombocytopenia is the occurrence of intracranial hemorrhage, leading to death or neurological sequelea. The diagnosis is straightforward when a maternal alloantibody is detected and the offending antigen identified in the infant. Any difficulties in confirming the diagnosis should not delay the treatment. Since the first description of these conditions in the 1950's, significant progress has been made in laboratory diagnosis and management.