Mismatch in the Classification of Linear Subspaces: Sufficient Conditions for Reliable Classification

This paper considers the classification of linear subspaces with mismatched classifiers. In particular, we assume a model where one observes signals in the presence of isotropic Gaussian noise and the distribution of the signals conditioned on a given class is Gaussian with a zero mean and a low-rank covariance matrix. We also assume that the classifier knows only a mismatched version of the parameters of input distribution in lieu of the true parameters. By constructing an asymptotic low-noise expansion of an upper bound to the error probability of such a mismatched classifier, we provide sufficient conditions for reliable classification in the low-noise regime that are able to sharply predict the absence of a classification error floor. Such conditions are a function of the geometry of the true signal distribution, the geometry of the mismatched signal distributions as well as the interplay between such geometries, namely, the principal angles and the overlap between the true and the mismatched signal subspaces. Numerical results demonstrate that our conditions for reliable classification can sharply predict the behavior of a mismatched classifier both with synthetic data and in a motion segmentation and a hand-written digit classification applications.Comment: 17 pages, 7 figures, submitted to IEEE Transactions on Signal Processin

Impulse oscillometry identifies peripheral airway dysfunction in children with adenosine deaminase deficiency.

Adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) is characterized by impaired T-, B- and NK-cell function. Affected children, in addition to early onset of infections, manifest non-immunologic symptoms including pulmonary dysfunction likely attributable to elevated systemic adenosine levels. Lung disease assessment has primarily employed repetitive radiography and effort-dependent functional studies. Through impulse oscillometry (IOS), which is effort-independent, we prospectively obtained objective measures of lung dysfunction in 10 children with ADA-SCID. These results support the use of IOS in the identification and monitoring of lung function abnormalities in children with primary immunodeficiencies

Gene therapy for the treatment of adenosine deaminase-deficient severe combined immune deficiency

Introduction: Adenosine deaminase (ADA) deficiency was the first human disease treated with gene therapy. Initial trials established proofs of concepts, but did not lead to cure of the severe combined immune deficiency that is the hallmark of this disease. A breakthrough trial combined gammaretroviral gene therapy with non-myeloablative conditioning of subjects unable to benefit from enzyme replacement therapy (ERT) with pegylated bovine ADA (PEG-ADA). Three additional trials have confirmed the ability of gene therapy to cure the clinical immune defect of ADA deficiency. Areas covered: This article reviews the development of gene therapy for ADA-SCID, compares the four trials that have been reported and discusses open questions remaining in the field. Expert opinion: Gene therapy may be regarded as standard of care for the majority of patients with ADA deficiency, along with allogeneic hematopoietic cell transplantation (HCT) or ERT. The appropriate sequencing of these treatments remains uncertain. While gammaretroviral gene therapy has been approved in Europe, remaining concerns about potential genotoxicity have led to further development, including the use of lentivirus vectors and modification of peri-transplant management. The ability of gene therapy to completely correct both the immunologic and non-immunologic manifestations of ADA deficiency remains to be demonstrated

Myeloid ELF1-like factor is a potent activator of interleukin-8 expression in hematopoietic cells

Myeloid ELF1-like factor (MEF), also known as ELF4, is a member of the ETS family of transcription factors which is expressed in hematopoietic cells. MEF-deficient mice have defects in natural killer cell and natural killer T cell development, suggesting a role for MEF in regulating innate immunity. MEF also functions in myeloid cells, where it can transactivate target genes. To identify MEF target genes in a "myeloid" environment, we created an inducible expression system and used oligonucleotide microarrays to examine the transcript profile of HEL cells after induction of MEF expression. Sixteen genes were reproducibly turned on or off more than 2-fold, 8 h after induction of MEF expression, and we examined one of the genes, interleukin-8 (IL-8), in greater detail. IL-8 is a CXC chemokine involved in neutrophil chemoattraction, angiogenesis, and stem cell mobilization. It is expressed by several tumor types, and its expression is regulated primarily transcriptionally. The IL-8 promoter contains three ETS binding sites, and we identified the specific site that binds MEF and is required for MEF responsiveness. MEF, but not the closely related ETS factors PEA3, ETS1, ETS2, ELF1, or PU.1, strongly activates the IL-8 promoter. MEF overexpression is sufficient to induce IL-8 protein expression, and reduction in MEF expression (using RNA interference) results in decreased IL-8 levels. These data demonstrates that MEF is an important regulator of IL-8 expression

Molecular biology of leukemia

Identification and characterization of leukemia-related chromosomal translocations have had significant impact on all aspects of the management of acute leukemia, including its diagnosis, assignment of prognosis, and development of an appropriate treatment plan. Several genes are recurrent targets of chromosomal abnormalities, suggesting that they play a key role in leukemogenesis. Significant progress has been made to define potentially unifying molecular mechanisms of leukemic transformation. Hopefully, these findings will provide the basis for molecularly targeted therapies for leukemia

Impulse oscillometry identifies peripheral airway dysfunction in children with adenosine deaminase deficiency.

Adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) is characterized by impaired T-, B- and NK-cell function. Affected children, in addition to early onset of infections, manifest non-immunologic symptoms including pulmonary dysfunction likely attributable to elevated systemic adenosine levels. Lung disease assessment has primarily employed repetitive radiography and effort-dependent functional studies. Through impulse oscillometry (IOS), which is effort-independent, we prospectively obtained objective measures of lung dysfunction in 10 children with ADA-SCID. These results support the use of IOS in the identification and monitoring of lung function abnormalities in children with primary immunodeficiencies

Quality of Life of Patients with Wiskott Aldrich Syndrome and X-Linked Thrombocytopenia: a Study of the Primary Immune Deficiency Consortium (PIDTC), Immune Deficiency Foundation, and the Wiskott-Aldrich Foundation.

BackgroundWe undertook a study to determine the impact of Wiskott Aldrich Syndrome (WAS) and X-linked thrombocytopenia (XLT) and their therapies upon the health-related quality of life (HRQOL) of patients and their families.Materials and methodsWe undertook a survey of patients and their families, who self-identified as having either WAS or XLT. We assessed the PedsQL™ 4.0, the parent proxy form, and the family impact module. These results were compared with normative data from previously published reports.ResultsSixty-eight patients (29 patients completed both the PedsQL™ 4.0 and the parent proxy form; 21 completed only the PedsQL™ 4.0; and 18 completed only the parent proxy form) were included. In contrast to patient-reported outcomes, parents of patients who had a bone marrow transplant (BMT) reported that their children had better QOL scores compared with those who did not (82.6 vs. 73.3, p = 0.023). The QOL of patients vs. previously published normative data showed decreases in patient scores for psychosocial health (72.62 vs. 86.58, p = < 0.001), emotional functioning (69.91 vs. 82.64, p = < 0.001), social functioning (77.55 vs. 91.56, p = < 0.001), and school functioning (70.46 vs. 85.67, p = < 0.001). The family impact study revealed deficits in emotional, social, and cognitive functioning, communication, and worry.ConclusionThese results show that patients with WAS/XLT are significantly impacted with respect to QOL. BMT offered a better QOL for patients according to parents, but not as reported by the patients. Future studies should incorporate QOL to provide more data and a better understanding of outcomes for long-term survivors and decision-making regarding BMT