Tensor-tensor algebra for optimal representation and compression of multiway data.

With the advent of machine learning and its overarching pervasiveness it is imperative to devise ways to represent large datasets efficiently while distilling intrinsic features necessary for subsequent analysis. The primary workhorse used in data dimensionality reduction and feature extraction has been the matrix singular value decomposition (SVD), which presupposes that data have been arranged in matrix format. A primary goal in this study is to show that high-dimensional datasets are more compressible when treated as tensors (i.e., multiway arrays) and compressed via tensor-SVDs under the tensor-tensor product constructs and its generalizations. We begin by proving Eckart-Young optimality results for families of tensor-SVDs under two different truncation strategies. Since such optimality properties can be proven in both matrix and tensor-based algebras, a fundamental question arises: Does the tensor construct subsume the matrix construct in terms of representation efficiency? The answer is positive, as proven by showing that a tensor-tensor representation of an equal dimensional spanning space can be superior to its matrix counterpart. We then use these optimality results to investigate how the compressed representation provided by the truncated tensor SVD is related both theoretically and empirically to its two closest tensor-based analogs, the truncated high-order SVD and the truncated tensor-train SVD.

The world apheresis association registry, 2023 update.

The WAA apheresis registry contains data on more than 140,000 apheresis procedures conducted in 12 different countries. The aim is to give an update of indications, type and number of procedures and adverse events (AEs). MATERIAL AND METHODS: The WAA-registry is used for registration of apheresis procedures and is free of charge. The responsible person for a center can apply at the site www.waa-registry.org RESULTS: Data includes reported AEs from 2012 and various procedures and diagnoses during the years 2018-2022; the latter in total from 27 centers registered a total of 9500 patients (41% women) that began therapeutic apheresis (TA) during the period. A total of 58,355 apheresis procedures were performed. The mean age was 50 years (range 0-94). The most common apheresis procedure was stem cell collection for which multiple myeloma was the most frequent diagnosis (51%). Donor cell collection was done in 14% and plasma exchange (PEX) in 28% of patients; In relation to all performed procedures PEX, using a centrifuge (35%) and LDL-apheresis (20%) were the most common. The main indication for PEX was TTP (17%). Peripheral veins were used in 56% as the vascular access. The preferred anticoagulant was ACD. AEs occurred in 2.7% of all procedures and were mostly mild (1%) and moderate 1.5% (needed supportive medication) and, only rarely, severe (0.15%). CONCLUSION: The data showed a wide range of indications and variability in apheresis procedures with low AE frequency.

Challenges associated with test dose pharmacokinetic predictions of high dose melphalan exposure in patients with multiple myeloma.

AIM: To evaluate the accuracy of melphalan test dose pharmacokinetic (PK) predictions of the subsequent high dose (HDM) area under the concentration-versus-time curve (AUC) and to identify sources of prediction error (PE). METHODS: A prospective multicentre PK study was conducted in 40 myeloma patients of median age 60 (range:35-71) years using a 20 mg/m2 test dose administered 1-3 days prior to HDM (predominantly 180 mg/m2). PK data were collected post the test and high doses to compare predicted versus actual AUCs determined using the trapezoidal rule. Test and high dose infusion concentration, volume and duration and the time from preparation to infusion were compared using the paired Wilcoxin rank sign test. The impact of Melphalan administration parameters on PE was evaluated using the Mann-Whitney test. The predictive capacity of a previously published population PK (PopPK) model was also examined. RESULTS: Predicted HDM AUC was within 15% of the observed values in only 63% of patients when analysed using the trapezoidal rule and 70% of patients using PopPK. Test dose infusion concentration, volume, duration and time from preparation to infusion were significantly lower than for HDM (p < 0.005). Test dose administration within 15 min of reconstitution (n = 5) was associated with significantly lower PE than administration times of 16-60 min (n = 22), p < 0.05. Test and HDM infusion concentrations were lower in patients with large PE (> ± 15%), but the differences were not significant (p = 0.078, 0.228, respectively). CONCLUSION: Test dose PK has the potential to predict subsequent HDM exposure to achieve a target AUC once melphalan administration parameters are optimised to account for stability issues in the formulation.

Boron Isotope Analysis Reveals Borate Selectivity in Seaweeds.

The role of boron in terrestrial plant physiology is diverse and increasingly well understood, but its role in marine aquatic eukaryotes is less clear. Our research reveals a distinctive and large offset in boron isotopes from seawater, irrespective of seaweed type or season. We show that the offset is consistent with the incorporation of borate from seawater. Boron is a known micronutrient in plants but very few studies have used boron isotopes to investigate boron's role in plant physiology. Seaweed, as the most primitive multicellular plant, has an important role in investigating wider plant adaptations that use boron to meet functional needs. Furthermore, seaweed and other plants are a key base nutrient provider in food webs, supplying boron to consumers and playing a critical role in boron environmental cycling.

Using the World Apheresis Association Registry Helps to Improve the Treatment Quality of Therapeutic Apheresis.

Therapeutic apheresis (TA) is prescribed to patients that suffer from a severe progressive disease that is not sufficiently treated by conventional medications. A way to gain more knowledge about this treatment is usually by the local analysis of data. However, the use of large quality assessment registries enables analyses of even rare findings. Here, we report some of the recent data from the World Apheresis Association (WAA) registry. Data from >104,000 procedures were documented, and TA was performed on >15,000 patients. The main indication for TA was the collection of autologous stem cells (45% of patients) as part of therapy for therapy. Collection of stem cells from donors for allogeneic transplantation was performed in 11% of patients. Patients with indications such as neurological diseases underwent plasma exchange (28%). Extracorporeal photochemotherapy, lipid apheresis, and antibody removal were other indications. Side effects recorded in the registry have decreased significantly over the years, with approximately only 10/10,000 procedures being interrupted for medical reasons. CONCLUSION: Collection of data from TA procedures within a multinational and multicenter concept facilitates the improvement of treatment by enabling the analysis of and feedback on indications, procedures, effects, and side effects.

Canonical Wnt signaling regulates patterning, differentiation and nucleogenesis in mouse hypothalamus and prethalamus.

The hypothalamus is a small, but anatomically and functionally complex region of the brain whose development is poorly understood. In this study, we have explored its development by studying the canonical Wnt signaling pathway, generating gain and loss of function mutations of beta-catenin (Ctnnb1) in both hypothalamic and prethalamic neuroepithelium. Deletion of Ctnnb1 resulted in an anteriorized and hypoplastic hypothalamus. Posterior structures were lost or reduced, and anterior structures were expanded. In contrast, overexpression of a constitutively active mutant form of Ctnnb1 resulted in severe hyperplasia of prethalamus and hypothalamus, and expanded expression of a subset of posterior and premamillary hypothalamic markers. Moderate defects in differentiation of Arx-positive GABAergic neural precursors were observed in both prethalamus and hypothalamus of Ctnnb1 loss of function mutants, while in gain of function mutants, their differentiation was completely suppressed, although markers of prethalamic progenitors were preserved. Multiple other region-specific markers, including several specific posterior hypothalamic structures, were also suppressed in Ctnnb1 gain of function mutations. Severe, region-specific defects in hypothalamic nucleogenesis were also observed in both gain and loss of function mutations of Ctnnb1. Finally, both gain and loss of function of Ctnnb1 also produced severe, non-cell autonomous disruptions of pituitary development. These findings demonstrate a central and multifaceted role for canonical Wnt signaling in regulating growth, patterning, differentiation and nucleogenesis in multiple diencephalic regions.

Foxd1 is required for terminal differentiation of anterior hypothalamic neuronal subtypes.

Although the hypothalamus functions as a master homeostat for many behaviors, little is known about the transcriptional networks that control its development. To investigate this question, we analyzed mice deficient for the Forkhead domain transcription factor Foxd1. Foxd1 is selectively expressed in neuroepithelial cells of the prethalamus and hypothalamus prior to the onset of neurogenesis, and is later restricted to neural progenitors of the prethalamus and anterior hypothalamus. During early stages of neurogenesis, we observed that Foxd1-deficient mice showed reduced expression of Six3 and Vax1 in anterior hypothalamus, but overall patterning of the prethalamus and hypothalamus is unaffected. After neurogenesis is complete, however, a progressive reduction and eventual loss of expression of molecular markers of the suprachiasmatic, paraventricular and periventricular hypothalamic is observed. These findings demonstrate that Foxd1 acts in hypothalamic progenitors to allow sustained expression of a subset of genes selectively expressed in mature neurons of the anterior hypothalamus.

Changes in Gene Expression in the Locus Coeruleus-Amygdala Circuitry in Inhibitory Avoidance PTSD Model.

The locus coeruleus (LC)-amygdala circuit is implicated in playing a key role in responses to emotionally arousing stimuli and in the manifestation of post-traumatic stress disorder (PTSD). Here, we examined changes in gene expression of a number of important mediators of the LC-amygdala circuitry in the inhibition avoidance model of PTSD. After testing for basal acoustic startle response (ASR), rats were exposed to a severe footshock (1.5 mA for 10 s) in the inhibitory avoidance apparatus. They were given contextual situational reminders every 5 day for 25 days. Controls were treated identically but with the footshock inactivated. Animals were re-tested on second ASR and decapitated 1 h later. The shock group had enhanced hyperarousal and several changes in gene expression compared to controls. In the LC, mRNA levels of norepinephrine (NE) biosynthetic enzymes (TH, DBH), NE transporter (NET), NPY receptors (Y1R, Y2R), and CB1 receptor of endocannabinoid system were elevated. In the basolateral amygdala (BLA), there were marked reductions in gene expression for CB1, and especially Y1R, with rise for corticotropin-releasing hormone (CRH) system (CRH, CRH receptor 1), and no significant changes in the central amygdala. Our results suggest a fast forward mechanism in the LC-amygdala circuitry in the shock group.

Prevalence of Chronic Illness among Youth with DSM-IV-TR Axis I Diagnoses at a Large Mental Health Agency in Northeast Ohio.

This descriptive study examines the prevalence of comorbid physical and mental health issues among young clients at a large mental health agency. Health status data was collected from the intake process of youth seeking mental health services at a Northeast Ohio agency (n = 1,076). The results show a higher prevalence of asthma and obesity among clients with known mental health diagnoses at this agency compared to national averages. The results could help the agency develop strategies for implementation of an integrated care model to better meet the complex needs of the clients served.

A CD2 high-expressing stress-resistant human plasmacytoid dendritic-cell subset.

Human plasmacytoid dendritic cells (pDCs) were considered to be a phenotypically and functionally homogeneous cell population; however, recent analyses indicate potential heterogeneity. This is of major interest, given their importance in the induction of anti-viral responses and their role in creating immunologically permissive environments for human malignancies. For this reason, we investigated the possible presence of human pDC subsets in blood and bone marrow, using unbiased cell phenotype clustering and functional studies. This defined two major functionally distinct human pDC subsets, distinguished by differential expression of CD2. The CD2(hi) and CD2(lo) pDCs represent discontinuous subsets, each with hallmark pDC functionality, including interferon-alpha production. The rarer CD2(hi) pDC subset demonstrated a significant survival advantage over CD2(lo) pDC during stress and upon exposure to glucocorticoids (GCs), which was associated with higher expression of the anti-apoptotic molecule BCL2. The differential sensitivity of these two human pDC subsets to GCs is demonstrated in vivo by a relative increase in CD2(hi) pDC in multiple myeloma patients treated with GCs. Hence, the selective apoptosis of CD2(lo) pDC during stress represents a novel mechanism for the control of innate responses.

Incidence of heterotopic ossification in direct anterior vs posterior approach to total hip arthroplasty: a retrospective radiographic review.

PURPOSE: To investigate the prevalence of heterotopic ossification following direct anterior approach total hip arthroplasty compared to posterior approach, performed by a single surgeon at one institution METHODS: All primary THAs performed by the senior author (JEL) over a 70-month period were reviewed, including 235 DAA and 120 posterior THAs. Brooker's system was used to grade HO at a minimum of six months follow-up. RESULTS: Patients undergoing DAA were less likely to develop clinically significant HO compared to posterior THA (p = 0.04). The overall incidence of HO following DAA THA was 24.3 % (3 % grade 3 and 0 % grade 4), and following posterior THA was 27.5 % (4.2 % grade 3 and 3.3 % grade 4). CONCLUSIONS: Lower rates of clinically significant (Brooker grade 3 and 4) HO were observed in DAA THA than in posterior approach THA. This data may be instructive when approaching THA candidates with conditions that predispose them to HO.

The LIM homeodomain factor Lhx2 is required for hypothalamic tanycyte specification and differentiation.

Hypothalamic tanycytes, a radial glial-like ependymal cell population that expresses numerous genes selectively enriched in embryonic hypothalamic progenitors and adult neural stem cells, have recently been observed to serve as a source of adult-born neurons in the mammalian brain. The genetic mechanisms that regulate the specification and maintenance of tanycyte identity are unknown, but are critical for understanding how these cells can act as adult neural progenitor cells. We observe that LIM (Lin-11, Isl-1, Mec-3)-homeodomain gene Lhx2 is selectively expressed in hypothalamic progenitor cells and tanycytes. To test the function of Lhx2 in tanycyte development, we used an intersectional genetic strategy to conditionally delete Lhx2 in posteroventral hypothalamic neuroepithelium, both embryonically and postnatally. We observed that tanycyte development was severely disrupted when Lhx2 function was ablated during embryonic development. Lhx2-deficient tanycytes lost expression of tanycyte-specific genes, such as Rax, while also displaying ectopic expression of genes specific to cuboid ependymal cells, such as Rarres2. Ultrastructural analysis revealed that mutant tanycytes exhibited a hybrid identity, retaining radial morphology while becoming multiciliated. In contrast, postnatal loss of function of Lhx2 resulted only in loss of expression of tanycyte-specific genes. Using chromatin immunoprecipitation, we further showed that Lhx2 directly regulated expression of Rax, an essential homeodomain factor for tanycyte development. This study identifies Lhx2 as a key intrinsic regulator of tanycyte differentiation, sustaining Rax-dependent activation of tanycyte-specific genes while also inhibiting expression of ependymal cell-specific genes. These findings provide key insights into the transcriptional regulatory network specifying this still poorly characterized cell type.

Stable tensor neural networks for efficient deep learning.

Learning from complex, multidimensional data has become central to computational mathematics, and among the most successful high-dimensional function approximators are deep neural networks (DNNs). Training DNNs is posed as an optimization problem to learn network weights or parameters that well-approximate a mapping from input to target data. Multiway data or tensors arise naturally in myriad ways in deep learning, in particular as input data and as high-dimensional weights and features extracted by the network, with the latter often being a bottleneck in terms of speed and memory. In this work, we leverage tensor representations and processing to efficiently parameterize DNNs when learning from high-dimensional data. We propose tensor neural networks (t-NNs), a natural extension of traditional fully-connected networks, that can be trained efficiently in a reduced, yet more powerful parameter space. Our t-NNs are built upon matrix-mimetic tensor-tensor products, which retain algebraic properties of matrix multiplication while capturing high-dimensional correlations. Mimeticity enables t-NNs to inherit desirable properties of modern DNN architectures. We exemplify this by extending recent work on stable neural networks, which interpret DNNs as discretizations of differential equations, to our multidimensional framework. We provide empirical evidence of the parametric advantages of t-NNs on dimensionality reduction using autoencoders and classification using fully-connected and stable variants on benchmark imaging datasets MNIST and CIFAR-10.

Prenatal diagnosis of spontaneous septostomy in dichorionic diamniotic twins and review of the literature.

OBJECTIVE: We present 2 cases of spontaneous septostomy in dichorionic diamniotic twins and review the literature regarding the incidence, etiology, and complications of this condition. METHODS: The following key words were used in the literature search: "rupture dividing membrane twin," "disruption dividing membrane twin," "pseudomonoamniotic twin," "spontaneous septostomy twin," "interfetal membrane disruption," "intertwin membrane rupture," and "intertwin membrane disruption." RESULTS: We present 2 cases in which an intertwin membrane defect was found prenatally in dichorionic diamniotic twins. In both cases, a portion of one twin's body was found traversing the spontaneous septostomy and in the sac of its cotwin. Umbilical cord Doppler studies showed no abnormalities in either case as the cord crossed the membrane disruption. In both cases, the fetuses had no notable sequelae from the ruptured intertwin membrane. The literature review revealed no cases of spontaneous septostomy in dichorionic diamniotic twins but 15 cases in monochorionic diamniotic twins. Possible etiologies include chorioamnionitis, trauma or physical rupture by the fetuses, developmental disturbances represented by amniotic plica, and polyhydramnios. In cases of monozygotic twins, a vascular etiology could explain this rare defect with formation of anastomoses of the outer embryonic vasculature. Complications of the spontaneous septostomy cases identified in the literature included cord entanglement (8 cases), preterm delivery (9 cases), and death (8 cases), although our 2 cases had minimal complications. CONCLUSIONS: Spontaneous septostomy in dichorionic diamniotic twins has not previously been reported.

Early Correction of Distal Radius Partial Articular Malunion Leads to Good Long-term Functional Recovery at Mean Follow-up of 4 Years.

Background: Distal radius articular step-off or deformity may cause posttraumatic arthritis and poor functional outcome. The purpose of this study was to evaluate pain and functional outcomes in patients with malunited partial articular distal radius fractures who underwent corrective osteotomy. We hypothesized that anatomic restoration of distal radius articular surface after a malunited partial articular distal radius fracture results in improvement in pain and functional measures and delays the development of posttraumatic arthritis. Methods: Seven consecutive patients with mean age of 38 years underwent corrective osteotomy via either a standard dorsal approach or combined dorsal and volar approach. Mean time from injury to corrective osteotomy was 10 weeks. Patients were assessed with respect to Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH), forearm and wrist range of motion, pain, and grip strength. Results: At mean follow-up of 44 months, significant improvements in pain scores (7.1-0.9, P < .001), QuickDASH (38.7-11.6, P < .001), grip strength (21.4-30.0 kg, P = .01) were achieved. All range of motion measurements demonstrated significant improvements except forearm pronation. One patient demonstrated radiographic evidence of osteoarthritis but had no pain at final follow-up. No patients required secondary surgery for removal of symptomatic hardware. Conclusions: Based on these findings, we recommend that early corrective osteotomies should be considered in young patients with intra-articular distal radius malunions before considering salvage procedures such as partial or complete wrist arthrodesis.

Distinguishing human peripheral blood CD16+ myeloid cells based on phenotypic characteristics.

Myeloid lineage cells present in human peripheral blood include dendritic cells (DC) and monocytes. The DC are identified phenotypically as HLA-DR+ cells that lack major cell surface lineage markers for T cells (CD3), B cells (CD19, CD20), NK cells (CD56), red blood cells (CD235a), hematopoietic stem cells (CD34), and Mo that express CD14. Both DC and Mo can be phenotypically divided into subsets. DC are divided into plasmacytoid DC, which are CD11c- , CD304+ , CD85g+ , and myeloid DC that are CD11c+ . The CD11c+ DC are readily classified as CD1c+ DC and CD141+ DC. Monocytes are broadly divided into the CD14+ CD16- (classical) and CD14dim CD16+ subsets (nonclassical). A population of myeloid-derived cells that have DC characteristics, that is, HLA-DR+ and lacking lineage markers including CD14, but express CD16 are generally clustered with CD14dim CD16+ monocytes. We used high-dimensional clustering analyses of fluorescence and mass cytometry data, to delineate CD14+ monocytes, CD14dim CD16+ monocytes (CD16+ Mo), and CD14- CD16+ DC (CD16+ DC). We sought to identify the functional and kinetic relationship of CD16+ DC to CD16+ Mo. We demonstrate that differentiation of CD16+ DC and CD16+ Mo during activation with IFNγ in vitro and as a result of an allo-hematopoietic cell transplant (HCT) in vivo resulted in distinct populations. Recovery of blood CD16+ DC in both auto- and allo-(HCT) patients after myeloablative conditioning showed similar reconstitution and activation kinetics to CD16+ Mo. Finally, we show that expression of the cell surface markers CD300c, CCR5, and CLEC5a can distinguish the cell populations phenotypically paving the way for functional differentiation as new reagents become available.

Characterizing rehabilitation services for patients with knee and hip replacement in skilled nursing facilities and inpatient rehabilitation facilities.

OBJECTIVE: To characterize rehabilitation services for patients with knee and hip replacement in 3 types of postacute facilities in the U.S. DESIGN: Multi-site prospective observational cohort study. SETTING: Eight freestanding skilled nursing facilities (SNFs), 1 hospital-based SNF, and 11 inpatient rehabilitation facilities (IRFs). PARTICIPANTS: Patients (N=2158) with knee or hip replacement. INTERVENTIONS: No new interventions. MAIN OUTCOME MEASURES: Length of stay (LOS), amount and intensity of physical therapy (PT) and occupational therapy (OT), types of therapy activities. RESULTS: Average LOS was about 15 days for freestanding SNF patients, and 9 to 10 days for hospital-based SNF and IRF patients. Freestanding SNFs and IRFs provide about the same number of hours of PT and OT; the hospital-based SNF provided 27% fewer hours. Freestanding SNFs and the hospital-based SNF provided fewer hours a day than did IRFs. Joint replacement patients across all 3 types of facilities spent, on average, 70% to 75% of their PT time in just 2 activities--exercise and gait and spent 56% to 66% of their OT time in 3 activities--exercise, functional mobility, and dressing lower body. CONCLUSIONS: Both freestanding SNFs and IRFs provided similar amounts of PT with a similar emphasis on exercise and gait activities. IRFs, however, provided more OT than freestanding SNFs. IRFs had shorter LOSs and more intensive therapy services than freestanding SNFs. Study freestanding SNFs exhibited greater variation in LOS and intensity of therapy than IRFs.

Determinants of Pain and Predictors of Pain Relief after Ulnar Shortening Osteotomy for Ulnar Impaction Syndrome.

Background The purpose of this study is to characterize patient- and surgery-specific factors associated with perioperative pain level in patients undergoing ulnar shortening osteotomy (USO) for ulnar impaction syndrome (UIS). We hypothesize that preoperative opiate consumption, tobacco utilization, and severity of ulnar variance will be associated with less postoperative pain relief. Methods All cases of USO between January 2010 and December 2016 for management of UIS were retrospectively reviewed. Patient demographics, smoking status, type of labor, and opioid utilization before surgery were recorded. Radiographic measurements for ulnar variance, radial tilt and inclination, as well as triangular fibrocartilage complex and distal radial-ulnar joint (DRUJ) morphology were assessed. Pre- and postoperative pain score were recorded. Regression analysis was performed to determine predictors of pain scores. Results A total of 69 patients were included for the final analysis with a mean age of 44 years (range 17-73 years). Seventeen patients reported use of daily opioid medications at the time of surgery (25%). Patients who used opioid analgesics daily, active laborers, smokers, and patients involved in worker compensation claims had significantly less pain relief after surgery. Patients with osteotomy performed at the metaphysis had significantly more pain relief than patients that had diaphyseal osteotomy. Regression analysis identified tobacco utilization and anatomic site of osteotomy as independent predictors of postoperative pain. Conclusion The results from this study identified smoking and location of osteotomy as independent predictors of postoperative pain relief. While smoking cessation is paramount to prevent delayed/nonunion it may also help improve pain relief following USO. The potential to achieve greater shortening with a metaphyseal osteotomy suggests that in addition to the mechanical unloading the carpus, pain relief after USO may also stem from tensioning the ulnar collateral ligaments of the wrist, the ECU subsheath, and the radioulnar ligaments. Level of Evidence This is a Level III, therapeutic study.

Examination of CD302 as a potential therapeutic target for acute myeloid leukemia.

Acute myeloid leukemia (AML) is the most common form of adult acute leukemia with ~20,000 new cases yearly. The disease develops in people of all ages, but is more prominent in the elderly, who due to limited treatment options, have poor overall survival rates. Monoclonal antibodies (mAb) targeting specific cell surface molecules have proven to be safe and effective in different haematological malignancies. However, AML target molecules are currently limited so discovery of new targets would be highly beneficial to patients. We examined the C-type lectin receptor CD302 as a potential therapeutic target for AML due to its selective expression in myeloid immune populations. In a cohort of 33 AML patients with varied morphological and karyotypic classifications, 88% were found to express CD302 on the surface of blasts and 80% on the surface of CD34+ CD38- population enriched with leukemic stem cells. A mAb targeting human CD302 was effective in mediating antibody dependent cell cytotoxicity and was internalised, making it amenable to toxin conjugation. Targeting CD302 with antibody limited in vivo engraftment of the leukemic cell line HL-60 in NOD/SCID mice. While CD302 was expressed in a hepatic cell line, HepG2, this molecule was not detected on the surface of HepG2, nor could HepG2 be killed using a CD302 antibody-drug conjugate. Expression was however found on the surface of haematopoietic stem cells suggesting that targeting CD302 would be most effective prior to haematopoietic transplantation. These studies provide the foundation for examining CD302 as a potential therapeutic target for AML.

Adult-onset Alexander disease with progressive ataxia and palatal tremor.

A novel glial fibrillary acidic protein (GFAP) mutation, Y257C, is reported in a patient with adult-onset Alexander disease. This is the oldest reported case with confirmation of a GFAP mutation. Onset was late in the sixth decade. Genetic analysis of the GFAP gene is recommended in cases of progressive ataxia and palatal tremor.