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Newborn screening (NBS) for spinal muscular atrophy (SMA) and severe combined immunodeficiency (SCID) faces challenges. Accurate and precise SMN1 and SMN2 copy number determination, confirmed by two orthogonal methods, are vital for SMA prognostication and treatment. Single SMN1 copy detection also enables the further feasibility to screen for compound heterozygotes. In SCID, low-level T-cell receptor excision circle (TREC) quantification by quantitative PCR is imprecise, necessitating replicates for reliable results. An assay with enhanced accuracy, precision, and high throughput is warranted for NBS SMA and SCID. False positive of SMN1 deletions due to allele dropout are also a potential pitfall in PCR-based methods. We evaluated a first-tier fully automated quadruplex droplet digital PCR (ddPCR) assay detecting SMN1, SMN2, TREC, and RPP30 using dried blood spots together with a second-tier Sanger sequencing to exclude SMN1 allele dropout. Five proficiency test samples and six patient samples with known SMN1 and SMN2 copy numbers confirmed by multiplex ligation-dependent probe amplification were used for accuracy evaluation with full concordance. The ddPCR assay showed high precision for SMN1 and SMN2 (<7% coefficient of variation (CV) for ≥0 copy) and TREC (14.6% CV at 37 copies/µL blood). Second-tier Sanger sequencing identified all SMA cases with homozygous deletions. Accuracy for TREC classification was concordant with 10 proficiency samples. The reference interval of TREC concentration was established for newborns ≥ 34 weeks (n = 1812) and the 2.5th percentile was 57 copies/µL blood. A two-tiered approach with fully automated quadruplex ddPCR and Sanger sequencing delivers accurate and precise quantitation for NBS SMA and SCID, enabling early treatment and counseling.

Diagnosing plasma conditions can give great advantages in optimizing plasma wakefield accelerator experiments. One possible method is that of photon acceleration. By propagating a laser probe pulse through a plasma wakefield and extracting the imposed frequency modulation, one can obtain an image of the density modulation of the wakefield. In order to diagnose the wakefield parameters at a chosen point in the plasma, the probe pulse crosses the plasma at oblique angles relative to the wakefield. In this paper, mathematical expressions relating the frequency modulation of the laser pulse and the wakefield density profile of the plasma for oblique crossing angles are derived. Multidimensional particle-in-cell simulation results presented in this paper confirm that the frequency modulation profiles and the density modulation profiles agree to within 10%. Limitations to the accuracy of the measurement are discussed in this paper. This technique opens new possibilities to quantitatively diagnose the plasma wakefield density at known positions within the plasma column.

In this study, we evaluated the implementation of a second-tier genetic screening test using an amplicon-based next-generation sequencing (NGS) panel in our laboratory during the period of 1 September 2021 to 31 August 2022 for the newborn screening (NBS) of six conditions for inborn errors of metabolism: citrullinemia type II (MIM #605814), systemic primary carnitine deficiency (MIM #212140), glutaric acidemia type I (MIM #231670), beta-ketothiolase deficiency (#203750), holocarboxylase synthetase deficiency (MIM #253270) and 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (MIM # 246450). The custom-designed NGS panel can detect sequence variants in the relevant genes and also specifically screen for the presence of the hotspot variant IVS16ins3kb of SLC25A13 by the copy number variant calling algorithm. Genetic second-tier tests were performed for 1.8% of a total of 22,883 NBS samples. The false positive rate for these six conditions after the NGS second-tier test was only 0.017%, and two cases of citrullinemia type II would have been missed as false negatives if only biochemical first-tier testing was performed. The confirmed true positive cases were citrullinemia type II (n = 2) and systemic primary carnitine deficiency (n = 1). The false positives were later confirmed to be carrier of citrullinemia type II (n = 2), carrier of glutaric acidemia type I (n = 1) and carrier of systemic primary carnitine deficiency (n = 1). There were no false negatives reported. The incorporation of a second-tier genetic screening test by NGS greatly enhanced our program’s performance with 5-working days turn-around time maintained as before. In addition, early genetic information is available at the time of recall to facilitate better clinical management and genetic counseling.

One obstacle in plasma accelerator development is the limitation of techniques to diagnose and measure plasma wakefield parameters. In this paper, we present a novel concept for the density measurement of a plasma wakefield using photon acceleration, supported by extensive particle in cell simulations of a laser pulse that copropagates with a wakefield. The technique can provide the perturbed electron density profile in the laser’s reference frame, averaged over the propagation length, to be accurate within 10%. We discuss the limitations that affect the measurement: small frequency changes, photon trapping, laser displacement, stimulated Raman scattering, and laser beam divergence. By considering these processes, one can determine the optimal parameters of the laser pulse and its propagation length. This new technique allows a characterization of the density perturbation within a plasma wakefield accelerator.

DNAJC12 deficiency is a recently described inherited metabolic disorder resulting in hyperphenylalaninemia and neurotransmitter deficiency. The effect of treatment on the prevention of neurological manifestations in this newly reported and heterogenous disorder is not fully understood, and the optimal treatment strategy remains to be elucidated. The global or regional incidence of the disease is yet to be estimated. Here, we report the first individual diagnosed with DNAJC12 deficiency in Hong Kong; the condition was picked up by newborn screening due to hyperphenylalaninemia after ruling out phenylalanine hydroxylase deficiency and other tetrahydrobiopterin related disorders. Compound heterozygous variants in the DNAJC12 gene were identified, which included a novel missense change and a nonsense pathogenic variant. Treatment with neurotransmitter precursors (tetrahydrobiopterin, levodopa, and oxitriptan) was initiated at four months of age, and dietary protein restriction was started at four years and six months of age. He remains asymptomatic at four and a half years of age, apart from having mildly impaired socio-communication and language development. In this report, we discuss the current diagnostic approach to hyperphenylalaninemia in newborn screening and the uncertainties that exist in the clinical outcome from earlier detection, treatment, and monitoring of DNAJC12-deficiency patients.

Dried blood spot (DBS) cards from newborn screening (NBS) programs represent a wealth of biological data. They can be stored easily for a long time, have the potential to support medical and public health research, and have secondary usages such as quality assurance and forensics, making it the ideal candidate for bio-banking. However, worldwide policies vary with regard to the duration of storage of DBS cards and how it can be used. Recent advances in genomics have also made it possible to perform extended genetic testing on DBS cards in the newborn period to diagnose both actionable and non-actionable childhood and adult diseases. Both storage and secondary uses of DBS cards raise many ethical, clinical, and social questions. The openness of the key stakeholders, namely, parents and healthcare providers (HCPs), to store the DBS cards, and for what duration and purposes, and to extended genetic testing is largely dependent on local cultural–social-specific factors. The study objective is to assess the parents’ and HCPs’ awareness and receptivity toward DBS retention, its secondary usage, and extended genetic testing. A cross-sectional, self-administrated survey was adopted at three hospitals, out of which two were public hospitals with maternity services, between June and December 2022. In total, 452 parents and 107 HCPs completed and returned the survey. Overall, both HCPs and parents were largely knowledgeable about the potential benefits of DBS card storage for a prolonged period and its secondary uses, and they supported extended genetic testing. Knowledge gaps were found in respondents with a lower education level who did not know that a DBS card could be stored for an extended period (p < 0.001), could support scientific research (p = 0.033), and could aid public health research, and future policy implementation (p = 0.030). Main concerns with regard to DBS card storage related to potential privacy breaches and anonymity (Parents 70%, HCPs 60%). More parents, compared to HCPs, believed that storing DBS cards for secondary research does not lead to a reciprocal benefit to the child (p < 0.005). Regarding extended genetic testing, both groups were receptive and wanted to know about actionable childhood- and adult-onset diseases. More parents (four-fifths) rather than HCPs (three-fifths) were interested in learning about a variant with unknown significance (p < 0.001). Our findings report positive support from both parents and HCPs toward the extended retention of DBS cards for secondary usage and for extended genetic testing. However, more efforts to raise awareness need to be undertaken in addition to addressing the ethical concerns of both parents and HCPs to pave the way forward toward policy-making for DBS bio-banking and extended genetic testing in Hong Kong.

Newborn screening (NBS) is an important public health program that aims to identify pre-symptomatic healthy babies that will develop significant disease if left undiagnosed and untreated. The number of conditions being screened globally is expanding rapidly in parallel with advances in technology, diagnosis, and treatment availability for these conditions. In Hong Kong, NBS for inborn errors of metabolism (NBSIEM) began as a pilot program in October 2015 and was implemented to all birthing hospitals within the public healthcare system in phases, with completion in October 2020. The number of conditions screened for increased from 21 to 24 in April 2016 and then to 26 in October 2019. The overall recruitment rate of the NBS program was 99.5%. In the period between October 2015 and December 2022, 125,688 newborns were screened and 295 were referred back for abnormal results. The recall rate was reduced from 0.26% to 0.12% after the implementation of second-tier testing. An inherited metabolic disorder (IMD) was eventually confirmed in 47 infants, making the prevalence of IMD in Hong Kong 1 in 2674. At the time of the NBS result, 78.7% of the newborns with IMD were asymptomatic. There were two deaths reported: one newborn with methylmalonic acidemia cobalamin B type (MMACblB) died after the initial crisis and another case of carnitine palmitoyltransferase II deficiency (CPTII) died at 18 months of age after metabolic decompensation. The most common IMD noted were disorders of fatty acid oxidation metabolism (40%, 19 cases), closely followed by disorders of amino acid metabolism (38%, 18 cases), with carnitine uptake defect (19.1%, 9 cases) and citrullinemia type II (17%, 8 cases) being the two most common IMD picked up by the NBSIEM in Hong Kong. Out of the all the IMDs identified, 19.1% belonged to diverse ethnic groups. False negative cases were reported for citrullinemia type II and congenital adrenal hyperplasia during this period.

Objective: The purpose of this study was to apply Ajzen's theory of planned behavior (TPB) and a measure of past physical activity behavior to predict first-year students' physical activity intentions and behavior. Participants and Methods: First-year university students (N = 212) completed measures of TPB variables and past physical activity at the start of the 2006 fall semester and a measure of physical activity 8 weeks later. Results: The TPB variables explained 37% of the variance in intentions, increasing to 39% with the addition of past behavior. Logistic regression showed that past behavior predicted whether students met Health Canada standards for being physically active (4 sessions of moderate/vigorous physical activity per week). Conclusions: Findings are consistent with other research showing that the TPB offers a good prediction of physical activity intentions but falls short of predicting behavior.

Objective: The purpose of this study was to identify the health topics students received information about, how students obtained health-related information, and perceived believability of those sources. Participants and Methods: Students (N = 1202) were surveyed using the National College Health Assessment (NCHA) of the American College Health Association. Results: Nearly half (46%) of the sample reported not receiving any information, whereas only 0.5% received information on all health topics. The Internet was the most common source of health-related information, but, conversely, was perceived as the least believable source. Health center medical staff and university health educators were perceived to be the most believable sources. Conclusions: Future practice at the university setting should focus on delivering health information through believable messengers utilizing the most commonly reported sources of information. This may have implications towards how students shape their health-related social cognitions and subsequent behaviors.

Microalbuminuria in diabetes mellitus is a risk factor for cardiovascular disease. We hypothesized that microalbuminuria in type 2 diabetic patients is related to impaired cardiopulmonary function during exercise, and that the severity of impairment is correlated with the degree of microalbuminuria. Twenty of each of the following categories of subjects performed symptom-limited cardiopulmonary exercise testing on a cycle ergometer: (1) type 2 diabetic patients with normoalbuminuria (daily urinary albumin excretion [UAE] < 30 mg/d); (2) type 2 diabetic patients with microalbuminuria (daily UAE, 30 to 300 mg/d); and (3) normal control subjects. Oxygen consumption (▪o2) of patients with microalbuminuria was lower than that of control subjects at anaerobic threshold (AT) [p < 0.001], and was lower than both control subjects (p < 0.001) and patients with normoalbuminuria (p = 0.015) at peak exercise. There was a progressive worsening in gas exchange efficiency at the lungs, as measured by minute ventilation (▪e)/carbon dioxide production (▪co2) at AT or Δ▪e/Δ▪co2 slope, (p = 0.006 and p = 0.019, respectively) going from control subjects to patients with normoalbuminuria and then to patients with microalbuminuria. Left ventricular ejection fractions and BP were similar in patients with normoalbuminuria and microalbuminuria. More patients with microalbuminuria (n = 9) than with normoalbuminuria (n = 2) demonstrated diastolic dysfunction (p = 0.013). These 11 patients had lower peak ▪o2 values (p = 0.001) and higher daily UAE (p = 0.028). An inverse linear relationship was found between peak ▪o2 and log10 daily UAE (r = − 0.57, r2 = 0.29, p < 0.001). Abnormalities reflecting reduced oxygen transport and impaired gas exchange efficiency were found during exercise, and were especially profound in patients with microalbuminuria. These changes could be secondary to pulmonary microangiopathy and myocardial interstitial changes. Increases in capillary permeability to proteins may take place in the myocardium as they do in the kidneys, and contribute to impaired myocardial distensibility and hence diastolic dysfunction.