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Biomedical subjects

A Khan

Publications and source records attributed to A Khan.

At least 19 recordsLinked to original sources

Genome-targeted enrichment and sequencing of human-infecting Cryptosporidium spp.

Cryptosporidium spp. are parasites that cause severe illness in vulnerable human populations. Obtaining pure and sufficient Cryptosporidium DNA from clinical and environmental samples is a challenging task. Oocysts shed in available fecal samples can be limited in quantity, require purification (biased towards dominant strains), and yield limited DNA (&#x2009;<&#x2009;40 fg/oocyst). Here, we use updated genomic sequences from a broad diversity of Cryptosporidium species that have been found to infect humans (C. cuniculus, C. hominis, C. meleagridis, C. parvum, C. tyzzeri, and C. viatorum) to develop and validate a set of 100,000 RNA baits (CryptoCap_100k) with the aim of enriching Cryptosporidium DNA from varied samples. Compared to unenriched libraries, CryptoCap_100k increases the percentage of reads mapping to target genome sequences, increases the depth and breadth of genome coverage, and facilitates analyses of genetic variants in many samples, while decreasing overall costs.

Cryptosporidium↗

GENOME TARGETED ENRICHMENT AND SEQUENCING OF HUMAN-INFECTING CRYPTOSPORIDIUM spp.

Cryptosporidium spp. are parasites that cause severe illness in vulnerable human populations. Obtaining pure and sufficient Cryptosporidium DNA from clinical and environmental samples is a challenging task. Oocysts shed in available fecal samples can be limited in quantity, require purification (biased towards dominant strains), and yield limited DNA (<40 fg/oocyst). Here, we use updated genomic sequences from a broad diversity of human-infecting Cryptosporidium species ( C. cuniculus , C. hominis , C. meleagridis , C. parvum , C. tyzzeri , and C. viatorum ) to develop and validate a set of 100,000 RNA baits (CryptoCap_100k) with the aim of enriching Cryptosporidium spp. DNA from varied samples. Compared to unenriched libraries, CryptoCap_100k increases the percentage of reads mapping to target genome sequences, increases the depth and breadth of genome coverage and the reliability of detecting species and mixed infections within a sample, and allows assessment of genetic variation via SNP calling, while decreasing costs.

Journal Article↗

WHOLE GENOME TARGETED ENRICHMENT AND SEQUENCING OF HUMAN-INFECTING CRYPTOSPORIDIUM spp.

Cryptosporidium spp. are protozoan parasites that cause severe illness in vulnerable human populations. Obtaining pure Cryptosporidium DNA from clinical and environmental samples is challenging because the oocysts shed in contaminated feces are limited in quantity, difficult to purify efficiently, may derive from multiple species, and yield limited DNA (<40 fg/oocyst). Here, we develop and validate a set of 100,000 RNA baits (CryptoCap_100k) based on six human-infecting Cryptosporidium spp. (C. cuniculus, C. hominis, C. meleagridis, C. parvum, C. tyzzeri, and C. viatorum) to enrich Cryptosporidium spp. DNA from a wide array of samples. We demonstrate that CryptoCap_100k increases the percentage of reads mapping to target Cryptosporidium references in a wide variety of scenarios, increasing the depth and breadth of genome coverage, facilitating increased accuracy of detecting and analyzing species within a given sample, while simultaneously decreasing costs, thereby opening new opportunities to understand the complex biology of these important pathogens.

Journal Article↗

Phylogenomic reconstruction of Cryptosporidium spp. captured directly from clinical samples reveals extensive genetic diversity.

Cryptosporidium is a leading cause of severe diarrhea and mortality in young children and infants in Africa and southern Asia. More than twenty Cryptosporidium species infect humans, of which C. parvum and C. hominis are the major agents causing moderate to severe diarrhea. Relatively few genetic markers are typically applied to genotype and/or diagnose Cryptosporidium. Most infections produce limited oocysts making it difficult to perform whole genome sequencing (WGS) directly from stool samples. Hence, there is an immediate need to apply WGS strategies to 1) develop high-resolution genetic markers to genotype these parasites more precisely, 2) to investigate endemic regions and detect the prevalence of different genotypes, and the role of mixed infections in generating genetic diversity, and 3) to investigate zoonotic transmission and evolution. To understand Cryptosporidium global population genetic structure, we applied Capture Enrichment Sequencing (CES-Seq) using 74,973 RNA-based 120 nucleotide baits that cover ~92% of the genome of C. parvum. CES-Seq is sensitive and successfully sequenced Cryptosporidium genomic DNA diluted up to 0.005% in human stool DNA. It also resolved mixed strain infections and captured new species of Cryptosporidium directly from clinical/field samples to promote genome-wide phylogenomic analyses and prospective GWAS studies.

Cryptosporidium↗

Intravesical explosions during transurethral endoscopic procedures.

Every Urologist, during the course of fulguration treatment of bladder tumours, has at some time or another experienced small intravesical explosions usually manifesting as a "pop". Major intravesical explosions are rare but potentially devastating complications of transurethral endoscopic resections. The damage to the bladder can range from small mucosal tears to bladder rupture, which can either be intraperitoneal (requiring laparotomy and open bladder repair) or extraperitoneal. We review the literature on intravesical explosions to determine the aetiology of these explosions and suggest strategies to prevent these. A comprehensive literature search was performed using Medline and Ovid to obtain information using search terms: intravesical explosions, transurethral procedures, endoscopic procedures, diathermyIntravesical explosions occur due to the production of explosive gases during use of diathermy on human tissues. The most dangerous combination is hydrogen and oxygen. Hydrogen alone is not explosive and it only becomes explosive when admixed with oxygen. Oxygen is not produced in sufficient quantity during diathermy to cause explosions but can enter into the bladder from the atmosphere during endoscopic procedures. Careful operative technique (correct use of the Ellick evacuator bulb and reducing the frequency of manual irrigations of the bladder) with minimisation of the operative time and using the coagulation current at moderate power as well as judicious coagulation of tissues can reduce the risk of this dangerous complication arising.

Humans↗

Search for D0-D0 mixing and branching-ratio measurement in the decay D0-->K+ pi- pi0.

We analyze 230.4 fb;{-1} of data collected with the BABAR detector at the PEP-II e;{+}e;{-} collider at SLAC to search for evidence of D0-D[over ];{0} mixing using regions of phase space in the decay D;{0}-->K;{+}pi;{-}pi;{0}. We measure the time-integrated mixing rate R_{M}=(0.023_{-0.014};{+0.018}(stat.)+/-0.004(syst.))%, and R_{M}<0.054% at the 95% confidence level, assuming CP invariance. The data are consistent with no mixing at the 4.5% confidence level. We also measure the branching ratio for D;{0}-->K;{+}pi;{-}pi;{0} relative to D;{0}-->K;{-}pi;{+}pi;{0} to be (0.214+/-0.008(stat.)+/-0.008(syst.))%.

Journal Article↗

Observation of a new Ds meson decaying to DK at a mass of 2.86 GeV/c2.

We observe a new D_{s} meson with mass (2856.6+/-1.5_{stat}+/-5.0_{syst}) MeV/c;{2} and width (48+/-7_{stat}+/-10_{syst}) MeV/c;{2} decaying into D0K+ and D;{+}K_{S};{0}. In the same mass distributions, we also observe a broad structure with mass (2688+/-4_{stat}+/-3_{syst}) MeV/c;{2} and width (112+/-7_{stat}+/-36_{syst}) MeV/c;{2}. To obtain this result, we use 240 fb;{-1} of data recorded by the BABAR detector at the PEP-II asymmetric-energy e;{+}e;{-} storage rings at the Stanford Linear Accelerator Center running at center-of-mass energies near 10.6 GeV.

Journal Article↗

Measurement of the B-->pi l nu branching fraction and determination of absolute value of V(ub) with tagged B mesons.

We report a measurement of the B-->pi l nu branching fraction based on 211 fb(-1) of data collected with the BABAR detector. We use samples of B0 and B+ mesons tagged by a second B meson reconstructed in a semileptonic or hadronic decay and combine the results assuming isospin symmetry to obtain B(B(0)-->pi- l+ nu) = (1.33+/-0.17stat+/-0.11syst) x 10(-4). We determine the magnitude of the Cabibbo-Kobayashi-Maskawa matrix element absolute value V(ub) by combining the partial branching fractions measured in ranges of the momentum transfer squared and theoretical calculations of the form factor. Using a recent lattice QCD calculation, we find absolute value V(ub) = (4.5+/-0.5stat+/-0.3syst(+0.7) -0.5FF x 10(-3), where the last error is due to the normalization of the form factor.

Journal Article↗

Measurement of branching fractions and charge asymmetries in B decays to an eta meson and a K* meson.

We present measurements of branching fractions and charge asymmetries for the decays B-->etaK*, where K* indicates a spin 0, 1, or 2 Kpi system. The data sample corresponds to 344x10(6) BB pairs collected with the BABAR detector at the PEP-II asymmetric-energy e+ e- collider at SLAC. We measure the branching fractions (in units of 10(-6): B(B0-->etaK*0(892))=16.5+/-1.1+/-0.8, B(B+-->etaK*+(892))=18.9+/-1.8+/-1.3, B(B0-->eta(Kpi)0*0)=11.0+/-1.6+/-1.5, B(B+-->eta(Kpi)0*+)=18.2+/-2.6+/-2.6, B(B0-->etaK2*0(1430))=9.6+/-1.8+/-1.1, and B(B+-->etaK2*+(1430))=9.1+/-2.7+/-1.4. We also determine the charge asymmetries for all decay modes.

Journal Article↗

Measurements of branching fractions, polarizations, and direct CP-violation asymmetries in B-->rhoK* and B-->f0(980)K* decays.

We report searches for B-meson decays to the charmless final states rhoK* and f0(980)K* with a sample of 232x10(6) BB pairs collected with the BABAR detector at the PEP-II e+e- collider. We measure in units of 10(-6) the following branching fractions, where the first error quoted is statistical and the second systematic, or upper limits are given at the 90% confidence level: B(B+-->rho0K*+)<6.1, B(B+-->rho+K*0)=9.6+/-1.7+/-1.5, B(B0-->rho-K*+)<12.0, B(B0-->rho0K*0)=5.6+/-0.9+/-1.3, B(B+-->f0(980)K*+)=5.2+/-1.2+/-0.5, and B(B0-->f0(980)K*0)<4.3. For the significant modes, we also measure the fraction of longitudinal polarization and the charge asymmetry: fL(B+-->rho+K*0)=0.52+/-0.10+/-0.04, fL(B0-->rho0K*0)=0.57+/-0.09+/-0.08, ACP(B+-->rho+K*0)=-0.01+/-0.16+/-0.02, ACP(B0-->rho0K*0)=0.09+/-0.19+/-0.02, and ACP(B+-->f0(980)K*+)=-0.34+/-0.21+/-0.03.

Journal Article↗

Patellofemoral disorders presenting as bilateral locked knees in achondroplasia.

Patellofemoral disorders in achondroplasia, to our knowledge, have not been reported in the literature. We describe an unusual case of bilateral locked knees in an achondroplastic patient secondary to intra-articular subluxating patellae and symmetrical chondral flap lesions of the femoral trochlea which were treated by arthroscopic resection. We suggest that abnormal kinematics may cause patellofemoral complications in achondroplasia.

Achondroplasia↗

Observation of B+ --> K0K+ and B0 --> K0K0.

We report observations of the b --> d penguin-dominated decays B+ --> K0K+ and B0 --> K0K0 in 316 fb(-1) of e+ e- collision data collected with the BABAR detector. We measure the branching fractions B(B+ --> K0K+) = (1.61+/-0.44+/-0.09) x 10(-6) and B(B0 --> K0K0 = (1.08+/-0.28+/-0.11) x 10(-6) and the CP-violating charge asymmetry A(CP)(K0K+) = 0.10+/-0.26+/-0.03. Using a vertexing technique previously employed in several analyses of all-neutral final states containing kaons, we report the first measurement of time-dependent CP-violating asymmetries in B0 --> K(S)0K(S)0, obtaining S = -1.28(-0.73-0.16)(+0.80+0.11) and C = -0.40+/-0.41+/-0.06. We also report improved measurements of the branching fraction B(B+ --> K0 pi+) = (23.9+/-1.1+/-1.0) x 10(-6) and CP-violating charge asymmetry A(CP)(K0 pi+) = -0.029+/-0.039+/-0.010.

Journal Article↗

Measurement of the branching fraction and photon energy moments of B-->Xs gamma and A(CP)(B --> X(s+d gamma)).

The photon spectrum in B-->Xs gamma decay, where Xs is any strange hadronic state, is studied using a data sample of 88.5 x 10(6) e+ e- --> Upsilon(4S) --> BB decays collected by the BABAR experiment at the Stanford Linear Accelerator Center. The partial branching fraction, DeltaB(B --> Xs gamma) = (3.67+/-0.29(stat)+/-0.34(syst)+/-0.29(model)) x 10(-4), the first moment = 2.288+/-0.025+/-0.017+/-0.015 GeV, and the second moment E2(gamma) = 0.0328+/-0.0040+/-0.0023+/-0.0036 GeV2 are measured for the photon energy range 1.9 GeV < E gamma < 2.7 GeV. They are also measured for narrower E gamma ranges. The moments are then fit to recent theoretical calculations to extract the heavy quark expansion parameters m(b) and mu2(pi) and to extrapolate the partial branching fraction to E gamma > 1.6 GeV. In addition, the direct CP asymmetry A(CP)(B-->X(s+d gamma) is measured to be -0.110+/-0.115(stat)+/-0.017(syst).

Journal Article↗

Fractures of the sternum: the influence of non-invasive cardiac monitoring on management.

Management of sternal fractures often involves a protracted hospital stay. This is often based on serial electrocardiography (ECG) and cardiac enzyme measurement (AST, CK, LDH). This retrospective study examined all cases of sternal fracture presenting to our institution between October 1998 and February 2003. Seventy-two cases were identified, 52 of which had isolated sternal fractures. Of these, 11 (21%) patients had an elevation in all cardiac enzymes. Twenty-three (44%) had an increase in some but not all. A single patient with ECG changes had no elevation in cardiac enzymes. Those patients with elevated cardiac enzymes had a significantly longer stay of 5.5 days compared with 3.7 days (P < 0.05). No adverse outcome was recorded in either group. We conclude that ECG and estimation of cardiac enzymes in these patients are of limited benefit and, when abnormal, appear to be associated with a significantly protracted and probably unnecessary hospitalisation.

Accidents, Traffic↗

Observation of e(+)e(-) annihilation into the C = +1 hadronic final states rho(0)rho(0) and phirho(0).

We report the first observation of e(+)e(-) annihilation into states of positive C parity, namely, rho(0)rho(0) and phirho(0). The two states are observed in the pi(+)pi(-)pi(+)pi(-) and K(+)K(-)pi(+)pi(-) final states, respectively, in a data sample of 225 fb(-1) collected by the BABAR experiment at the Positron-Electron Project II e(+)e(-) storage rings at energies near sqrt[s]=10.58 GeV. The distributions of costheta(*), where theta(*) is the center-of-mass polar angle of the phi meson or the forward rho(0) meson, suggest production by two-virtual-photon annihilation. We measure cross sections within the range |costheta(*)|<0.8 of sigma(e(+)e(-)-->rho(0)rho(0))=20.7+/-0.7(stat)+/-2.7(syst) fb and sigma(e(+)e(-)-->phirho(0))=5.7+/-0.5(stat)+/-0.8(syst) fb.

Journal Article↗

Measurement of the spin of the omega(-) hyperon.

A measurement of the spin of the Omega(-) hyperon produced through the exclusive process Xi(c)(0)-->Omega(-)K(+) is presented using a total integrated luminosity of 116 fb(-1) recorded with the BABAR detector at the e(+)e(-) asymmetric-energy B factory at SLAC. Under the assumption that the Xi(c)(0) has spin 1/2, the angular distribution of the Lambda from Omega(-)-->LambdaK(-) decay is inconsistent with all half-integer Omega(-) spin values other than 3/2. Lower statistics data for the process Omega(c)(0)-->Omega(-)pi(+) from a 230 fb(-1) sample are also found to be consistent with Omega(-) spin 3/2. If the Xi(c)(0) spin were 3/2, an Omega(-) spin of 5/2 could not be excluded.

Journal Article↗

Observation of B0 meson decay to a 1 +/(1260)pi /+.

We present a measurement of the branching fraction of the decay B(0)-->a1 (+/)(1260)pi(/+) with a1 (+/)(1260)-->pi(/+)pi(+/)pi(+/). The data sample corresponds to 218 x 10(6) BB[over ] pairs produced in e+e- annihilation through the Upsilon(4S) resonance. We measure the branching fraction Beta(B(0)-->a1(+/)(1260)pi(/+))Beta(a1(+/)(1260)-->pi(/+)pi(+/)pi(+/)) = (16.6+/1.9+/1.5) x 10(-6), where the first error quoted is statistical and the second is systematic.

Journal Article↗

Isoform-dependent interaction of voltage-gated sodium channels with protons.

Protons are potent physiological modifiers of voltage-gated Na(+) channels, shifting the voltage range of channel gating and reducing current magnitude (pK(a) approximately 6). We recently showed that proton block of the skeletal muscle isoform (Na(V)1.4) resulted from protonation of the four superficial carboxylates in the outer vestibule of the channel. We concluded that the large local negative electrostatic field shifted the outer vestibule carboxylate pK(a) into the physiological range. However, block was not complete; the best-fit titration curves yielded an acid pH asymptote of 10-15%, suggesting that the selectivity filter carboxylates may not be protonated. Using HEK 293 cells stably expressing different isoforms, each with varying channel density, we demonstrate that a pH-independent current is found in Na(V)1.4, but not in the cardiac isoform (Na(V)1.5). Mutational studies showed that absence of the pH-independent current in Na(V)1.5 could be ascribed to the cysteine in domain I, just above the selectivity filter aspartate (Cys373). We suggest that this cysteine can be protonated in acid solution to produce a positive charge that blocks the pore. Competition between protons and Na(+) did not exist for Na(+) concentrations between 1 and 140 mm. The residual current in acid solution, when the cysteine is absent, confirms that over the range of pH values that can be achieved physiologically, the selectivity filter carboxylates are not protonated. The pH-independent current helps to protect activation of skeletal muscle during the acidosis that occurs during exercise.

Acidosis↗