There is an increasing body of work exploring the integration of random projection into algorithms for numerical linear algebra. The primary motivation is to reduce the overall computational cost of ...processing large datasets. A suitably chosen random projection can be used to embed the original dataset in a lower-dimensional space such that key properties of the original dataset are retained. These algorithms are often referred to as sketching algorithms, as the projected dataset can be used as a compressed representation of the full dataset. We show that random matrix theory, in particular the Tracy-Widom law, is useful for describing the operating characteristics of sketching algorithms in the tall-data regime when \(n \gg d\). Asymptotic large sample results are of particular interest as this is the regime where sketching is most useful for data compression. In particular, we develop asymptotic approximations for the success rate in generating random subspace embeddings and the convergence probability of iterative sketching algorithms. We test a number of sketching algorithms on real large high-dimensional datasets and find that the asymptotic expressions give accurate predictions of the empirical performance.
To evaluate the use of remote reading of digital retinal photographs in the diagnosis of severe (referral-warranted) retinopathy of prematurity (ROP) during longitudinal screening for ROP.
...Prospective, longitudinal cohort study.
Forty-four consecutive premature infants at risk for ROP.
All infants were examined longitudinally, over a series of examinations, by indirect ophthalmoscopy (gold standard) and digital photography using the RetCam-120 Digital Retinal Camera (Massie Research Laboratories Inc., Dublin, CA) equipped with an ROP lens. Images were stored and read remotely by a masked reader. Referral-warranted ROP was defined as ROP in zone 1, the presence of plus disease or the presence of any stage 3 ROP. We determined whether and when referral-warranted ROP was diagnosed for each eye, of each infant, on each examination, during the course of each of the infant's screening.
Severe (referral-warranted) ROP was diagnosed in 23 eyes by indirect ophthalmoscopy during their series of examinations. Digital photography had a sensitivity of 100% and a specificity of 96% in detecting referral-warranted ROP. The positive predictive value of digital photography was 92%, and the negative predictive value was 100%. In 87% of eyes, referral-warranted ROP was diagnosed by digital photography before or at the same time as indirect ophthalmoscopy.
Longitudinal remote reading of digital photographs using the RetCam-120 system has excellent specificity and sensitivity in detecting referral-warranted ROP. This pilot study has shown that remote reading of digital photographs has promise for telemedicine strategies in ROP screening.
Background There is interest in strategies to match recipients to red blood cell (RBC) units for transfusion using antigens beyond ABO/Rh/K with the aim of reducing rates of alloantibody formation in ...heavily transfused people, for example sickle cell disease (SCD) and thalassemia (THAL). However, the efficacy of different strategies, often defined in national guidelines, is unknown. People with SCD/THAL in England are now offered free universal blood group typing using high-throughput, low-cost genotyping arrays, which will also be applied to 92,000 blood donors, extending the antigens available for matching. Key to an evaluation of the potential benefits of improved matching is an understanding of the patterns of alloimmunization, which have been reported to vary widely in SCD and THAL. We describe the distribution of alloantibodies in people with SCD/THAL, and evaluate the effect of transfusion exposure on the incidence of antibody formation alongside national guidelines. Methods In 2019 we performed a cross-sectional service evaluation of transfusion treatment for recipients with SCD and THAL at three comprehensive care centres in London, comparing practices against current British Society Haematology (BSH) guidelines, which require matching for compatibility with ABO/Rh/K antigens. We collated and curated data on red cell antigens and antibodies and transfusion treatment regimens from hospital records. Subsequently, at the largest centre, we collated additional longitudinal data on antigens, antibodies and treatment from hospital records retrospectively for the 5 years ending on 31st December 2022. The longitudinal cohort overlapped substantially with the recipients contributing to the cross-sectional service evaluation. Appropriate local and national (22/EM/0006) governance approvals were obtained. Results For the service evaluation, we collated data on 2,025 people: 1,331 SCD (of whom 199 regularly transfused); 453 THAL (of whom 257 regularly transfused). The prevalence of at least one antibody was 14% and 20% in SCD and THAL recipients respectively, and 26% and 24% in regularly transfused SCD and THAL recipients respectively. The commonest antibodies in SCD were anti-S (3.2% prevalence), anti-E (2.9% prevalence), anti-Kp(a) (2.3% prevalence) and anti-K (2.1% prevalence); and in THAL were anti-K (7.1% prevalence), anti-E (6.8% prevalence), anti-Kp(a) (6.6% prevalence) and anti-C (2.2% prevalence). We collated longitudinal data on 676 people treated at the largest centre, of whom 443 had a complete five-year transfusion history. Over five years, 317 SCD recipients received 45,707 RBC units of whom 46 developed new antibodies (Table 1); 126 THAL recipients received 15,251 RBC units and two developed new antibodies. In total, there were 57 alloimmunization events in SCD recipients and 3 in THAL recipients. The antibodies with the greatest frequency of incident formation were anti-Kp(a) (14 events) and anti-C (12 events), all in SCD. For each antibody, we calculated the number of antigen negative units required to eliminate the possibility of incident alloimmunization in the cohort, assuming transfusion was equally distributed across antigen types e.g. 93% of the 676 recipients are Fy(a) neg, so 0.93 x 45,707 units = 42,508 Fy(a) negative units would need to be supplied over 5 years to ensure that no Fy(a) negative recipients are exposed to Fy(a) positive blood. Conclusions The risk of new alloimmunization differs between THAL and SCD. In SCD, anti-Kp(a) and anti-C account for almost 50% of new alloimmunization. Most of the antibodies (anti C/E/K) prevalent in our longitudinal cohort are likely to have been formed before the introduction of the current matching strategies defined in national guidelines. Many people who are antigen negative never form cognate antibodies to the corresponding antigen, despite extensive transfusion exposure. Guidance around extended matching beyond ABO/Rh/K may not match the antibodies that are most commonly newly formed in SCD, but may not be indicated in THAL. Further studies are required to determine who will benefit from more precise RBC matching, given the relative paucity of antigen negative blood in donor populations, such as planned by novel algorithmic real-time approaches in the Haem-Match programme (www.haemmatch.org).
Sketching is a probabilistic data compression technique that has been largely developed in the computer science community. Numerical operations on big datasets can be intolerably slow; sketching ...algorithms address this issue by generating a smaller surrogate dataset. Typically, inference proceeds on the compressed dataset. Sketching algorithms generally use random projections to compress the original dataset and this stochastic generation process makes them amenable to statistical analysis. We argue that the sketched data can be modelled as a random sample, thus placing this family of data compression methods firmly within an inferential framework. In particular, we focus on the Gaussian, Hadamard and Clarkson-Woodruff sketches, and their use in single pass sketching algorithms for linear regression with huge n. We explore the statistical properties of sketched regression algorithms and derive new distributional results for a large class of sketched estimators. We develop confidence intervals for sketching estimators and bounds on the relative efficiency of different sketching algorithms. An important finding is that the best choice of sketching algorithm in terms of mean square error is related to the signal to noise ratio in the source dataset. Finally, we demonstrate the theory and the limits of its applicability on two real datasets.
The autosomal recessive disorder primary congenital glaucoma (PCG) is caused by unknown developmental defect(s) of the trabecular meshwork and anterior chamber angle of the eye. Homozygosity mapping ...with a DNA pooling strategy in three large consanguineous Saudi PCG families identified the
GLC3A locus on chromosome 2p21 in a region tightly linked to PCG in another population. Formal linkage analysis in 25 Saudi PCG families confirmed both significant linkage to polymorphic markers in this region and incomplete penetrance, but it showed no evidence of genetic heterogeneity. For these 25 families, the maximum combined two-point LOD score was 15.76 at a recombination fraction of .021, with the polymorphic marker
D2S177. Both haplotype analysis and homozygosity mapping in these families localized
GLC3A to a 5-cM critical interval delineated by markers
D2S2186 and
D2S1356. Sequence analysis of the coding exons for cytochrome P4501B1
(CYP1B1) in these 25 families revealed three distinctive mutations that segregate with the phenotype in 24 families. Additional clinical and molecular data on some mildly affected relatives showed variable expressivity of PCG in this population. These results should stimulate a study of the genetic and environmental events that modify the effects of
CYP1B1 mutations in ocular development. Furthermore, the small number of PCG mutations identified in this Saudi population makes both neonatal and population screening attractive public health measures.
Background
Familial pseudohyperkalemia (FP) is characterized by an increased rate of potassium leakage in refrigerated red cells and is associated with the minor allele of the single nucleotide ...polymorphism rs148211042 (R723Q) in the ABCB6 gene. The study aims were to obtain the minor allele frequencies of ABCB6 variants and to measure supernatant potassium accumulation, and other red cell storage parameters, in red cell concentrates (RCC) from carriers of variant rs148211042 under standard blood bank conditions.
Study Design
Whole blood units were collected from 6 FP individuals and 11 controls and processed into RCC in additive solution. RCC were sampled and tested over cold storage for full blood count, extracellular potassium, glucose, lactate, microvesicle release, deformability, hemolysis, pH, adenosine triphosphate, and 2,3‐diphosphoglycerate.
Results
Screening of genotyped cohorts identified that variant rs148211042 is present in 1 in 394 British citizens of European ancestry. FP RCC had significantly higher supernatant potassium at all time points from day 3 onwards (p < .001) and higher mean cell volume (p = .032) than controls. The initial rate of potassium release was higher in FP RCC; supernatant potassium reached 46.0 (23.8–57.6) mmol/L (mean range) by day 5, increasing to 68.9 (58.8–73.7) mmol/L by day 35. Other quality parameters were not significantly different between FP RCC and controls.
Conclusion
These data suggest that if a blood donor has FP, reducing the RCC shelf‐life to 5 days may be insufficient to reduce the risk of hyperkalemia in clinical scenarios such as neonatal large volume transfusion.
Primary congenital glaucoma (PCG) is an autosomal recessive disorder associated with unknown developmental defect(s) in the anterior chamber. Recently, we reported three distinct mutations in CYP1B1, ...the gene for cytochrome P4501B1, in 25 Saudi families segregating PCG. For this report, we analyzed 37 additional families and confirmed the initial finding of decreased penetrance. Mutations and intragenic single-nucleotide polymorphisms (SNPs) were also analyzed from direct sequencing of all CYP1B1 coding exons. Eight distinct mutations were identified: G61E, R469W and D374N, the most common Saudi mutations, account for 72, 12 and 7%, respectively, of all the PCG chromosomes. Five additional homozygous mutations (two deletions and three missense mutations) were detected, each in a single family. Affected individuals from five families had no CYP1B1 coding mutations, and each family had a unique SNP profile. The identification of eight distinct mutations in a single gene, on four distinct haplotypes, suggests a relatively recent occurrence of multiple mutations in CYP1B1 in Saudi Arabia. These data demonstrate decreased penetrance of the PCG phenotype in the Saudi population, because 40 apparently unaffected individuals in 22 families have mutations and haplotypes identical to their affected siblings. Two individuals were subsequently diagnosed with glaucoma and two others had abnormal ocular findings that are consistent with milder forms of glaucoma. Analysis of these 22 kindreds suggests the presence of a dominant modifier locus that is not linked genetically to CYP1B1. Linkage and Southern analyses excluded three candidate modifier loci.
IMPORTANCE: Glaucoma can develop following cataract removal in children. OBJECTIVE: To assess the cumulative incidence of glaucoma-related adverse events (defined as glaucoma or glaucoma suspect) and ...factors associated with risk of these adverse events in the first 5 years after lensectomy prior to 13 years of age. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used longitudinal registry data collected at enrollment and annually for 5 years from 45 institutional and 16 community sites. Participants were children aged 12 years or younger with at least 1 office visit after lensectomy from June 2012 to July 2015. Data were analyzed from February through December 2022. EXPOSURES: Usual clinical care after lensectomy. MAIN OUTCOMES AND MEASURES: The main outcomes were cumulative incidence of glaucoma-related adverse events and baseline factors associated with risk of these adverse events. RESULTS: The study included 810 children (1049 eyes); 443 eyes of 321 children (55% female; mean SD age, 0.89 1.97 years) were aphakic after lensectomy, and 606 eyes of 489 children (53% male; mean SD age, 5.65 3.32 years) were pseudophakic. The 5-year cumulative incidence of glaucoma-related adverse events was 29% (95% CI, 25%-34%) in 443 eyes with aphakia and 7% (95% CI, 5%-9%) in 606 eyes with pseudophakia; 7% (95% CI, 5%-10%) of aphakic eyes and 3% (95% CI, 2%-5%) of pseudophakic eyes were diagnosed as glaucoma suspect. Among aphakic eyes, a higher risk for glaucoma-related adverse events was associated with 4 of 8 factors, including age less than 3 months (vs ≥3 months: adjusted hazard ratio aHR, 2.88; 99% CI, 1.57-5.23), abnormal anterior segment (vs normal: aHR, 2.88; 99% CI, 1.56-5.30), intraoperative complications at time of lensectomy (vs none; aHR, 2.25; 99% CI, 1.04-4.87), and bilaterality (vs unilaterality: aHR, 1.88; 99% CI, 1.02-3.48). Neither of the 2 factors evaluated for pseudophakic eyes, laterality and anterior vitrectomy, were associated with risk of glaucoma-related adverse events. CONCLUSIONS AND RELEVANCE: In this cohort study, glaucoma-related adverse events were common after cataract surgery in children; age less than 3 months at surgery was associated with elevated risk of the adverse events in aphakic eyes. Children with pseudophakia, who were older at surgery, less frequently developed a glaucoma-related adverse event within 5 years of lensectomy. The findings suggest that ongoing monitoring for the development of glaucoma is needed after lensectomy at any age.
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