•A historical shipwreck (La Belle) was discovered in 1995 off the coast of Texas•La Belle was part of the last expedition of the French explorer Sieur de La Salle•Two adult male skeletons were ...recovered during excavation of the ship•Massively parallel sequencing (MPS) was performed on each set of skeletal remains•Comprehensive forensic genetic testing yielded biogeographic ancestry, human identity, and phenotype data which, in conjunction with historical records, will assist genealogical investigations to identify the decedents
In 1995, the historical shipwreck of La Belle was discovered off the coast of Texas. One partial human skeleton was recovered from alongside cargo in the rear portion of the ship; a second (complete) skeleton was found atop coiled anchor rope in the bow. In late 2015, comprehensive forensic genetic testing began on multiple samplings from each set of remains. For the partial skeleton recovered from the ship’s rear cargo area, results were obtained for 26/27 Y-STRs using traditional CE; with MPS technology, results were obtained for 18/24 Y-STRs, 56/56 ancestry-informative SNPs (aiSNPs), 22/22 phenotype-informative SNPs (piSNPs), 22/27 autosomal STRs, 4/7 X-STRs, and 94/94 identity-informative SNPs (iiSNPs). For the complete skeleton of the second individual, results were obtained for 7/17 Y-STRs using traditional CE; with MPS technology, results were obtained for 5/24 Y-STRs, 49/56 aiSNPs, 18/22 piSNPs, 15/27 autosomal STRs, 1/7 X-STRs, and 66/94 iiSNPs. Biogeographic ancestry for each set of skeletal remains was predicted using the ancestry feature and metapopulation tool of the Y-STR Haplotype Reference Database (YHRD), Haplogroup Predictor, and the Forensic Research/Reference on Genetics knowledge base (FROG-kb). Phenotype prediction was performed using piSNP data and the HIrisplex eye color and hair color DNA phenotyping webtool. mtDNA whole genome sequencing also was performed successfully. This study highlights the sensitivity of current forensic laboratory methods in recovering DNA from historical and archaeological human remains. Using advanced sequencing technology provided by MiSeq™ FGx (Verogen) and Ion S5™ (Thermo Fisher Scientific) instrumentation, degraded skeletal remains can be characterized using a panel of diverse and highly informative markers, producing data which can be useful in both forensic and genealogical investigations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
ABSTRACTThis study evaluated the impact of a 4-week mandatory Neurology-Physical Medicine and Rehabilitation (N-PM&R) advanced-core clerkship for fourth-year medical students. The combined clerkship ...encouraged an interdisciplinary and function-based approach to the management of common neurologic, musculoskeletal, and pain complaints. Seventy-three fourth-year medical students participated in the rotation over one year. A survey assessing knowledge and skill set topics was conducted before and after the clerkship. Qualitative feedback regarding the rotation was provided by the students and analyzed. Significant gaps in knowledge and skill sets were identified prior to the clerkship and successfully addressed by combined teaching modalities. These data demonstrate that an integrated N-PM&R clerkship can improve students’ confidence in multiple domains. Integrating PM&R into core clerkships at other medical schools may provide an avenue to address curriculum gaps.
Tyrosine kinase inhibitors (TKIs) have been associated with improved survival of patients with chronic myeloid leukemia (CML) but are also associated with adverse effects, especially fatigue and ...diarrhea. Discontinuation of TKIs is safe and is associated with the successful achievement of treatment-free remission (TFR) for some patients.
To evaluate molecular recurrence (MRec) and patient-reported outcomes (PROs) after TKI discontinuation for US patients with CML.
The Life After Stopping TKIs (LAST) study was a prospective single-group nonrandomized clinical trial that enrolled 172 patients from 14 US academic medical centers from December 18, 2014, to December 12, 2016, with a minimum follow-up of 3 years. Participants were adults with chronic-phase CML whose disease was well controlled with imatinib, dasatinib, nilotinib, or bosutinib. Statistical analysis was performed from August 13, 2019, to March 23, 2020.
Discontinuation of TKIs.
Molecular recurrence, defined as loss of major molecular response (BCR-ABL1 International Scale ratio >0.1%) by central laboratory testing, and PROs (Patient-Reported Outcomes Measurement Information System computerized adaptive tests) were monitored. Droplet digital polymerase chain reaction (ddPCR) was performed on samples with undetectable BCR-ABL1 by standard real-time quantitative polymerase chain reaction (RQ-PCR).
Of 172 patients, 89 were women (51.7%), and the median age was 60 years (range, 21-86 years). Of 171 patients evaluable for molecular analysis, 112 (65.5%) stayed in major molecular response, and 104 (60.8%) achieved TFR. Undetectable BCR-ABL1 by either ddPCR or RQ-PCR at the time of TKI discontinuation (hazard ratio, 3.60; 95% CI, 1.99-6.50; P < .001) and at 3 months (hazard ratio, 5.86; 95% CI, 3.07-11.1; P < .001) was independently associated with MRec. Molecular recurrence for patients with detectable BCR-ABL1 by RQ-PCR was 50.0% (14 of 28), undetectable BCR-ABL1 by RQ-PCR but detectable by ddPCR was 64.3% (36 of 56), and undetectable BCR-ABL1 by both ddPCR and RQ-PCR was 10.3% (9 of 87) (P ≤ .001). Of the 112 patients in TFR at 12 months, 90 (80.4%) had a clinically meaningful improvement in fatigue, 39 (34.8%) had a clinically meaningful improvement in depression, 98 (87.5%) had a clinically meaningful improvement in diarrhea, 24 (21.4%) had a clinically meaningful improvement in sleep disturbance, and 5 (4.5%) had a clinically meaningful improvement in pain interference. Restarting a TKI resulted in worsening of PROs.
In this study, TKI discontinuation was safe, and 60.8% of patients remained in TFR. Discontinuation of TKIs was associated with improvements in PROs. These findings should assist patients and physicians in their decision-making regarding discontinuation of TKIs. Detectable BCR-ABL1 by RQ-PCR or ddPCR at the time of TKI discontinuation was associated with higher risk of MRec; clinical application of this finding should be confirmed in other studies.
ClinicalTrials.gov Identifier: NCT02269267.
•In 1932, seven burials were discovered on a Texas plantation (a former Caddo Indian village).•One set of skeletal remains (an adult male) was buried in a manner inconsistent with Caddo ...tradition.•Cranial measurements and dietary isotope data support European ancestry for this adult male.•Mitochondrial DNA sequencing revealed Haplogroup H or R (further support of European descent).•Historical records suggest this may be a member of the French explorer La Salle’s last expedition.
In 1932, seven burials were discovered on a Texas plantation that was originally the site of a 17th-century Caddo Indian village. Of the seven excavated graves, one set of remains (an adult male) was notably buried in a manner inconsistent with traditional Caddoan burial practices and has long been purported to be the remains of Sieur de Marle (a member of the French explorer La Salle’s last expedition). Diary accounts of La Salle’s expedition scribe report that Sieur de Marle died along a river near an Indian village during a trek to Canada to find help for colonists left behind at the ill-fated Fort St. Louis. Additionally, two lead projectiles recovered from the grave were ballistically analyzed and determined to be consistent with ammunition used in 17th-century weaponry. In the 1980s, anthropologists requested access to the remains for study, but the skull was missing. Cranial measurements recorded in 1940 and 1962 (by two independent anthropologists) were used to investigate the ancestry of this individual; and the Giles-Elliot (G-E) discriminant function was calculated to be 18.1, within the Anglo-European range. Dietary isotope testing on non-cranial skeletal elements determined that this unknown male’s diet was rich in animal/marine protein sources, which differs appreciably from Caddo Indian populations of that time period. In order to genetically assess this individual’s biogeographic ancestry and to provide further support that this individual is of European descent, mitochondrial DNA (mtDNA) sequencing was performed using the Applied Biosystems™ Precision ID mtDNA Whole Genome Panel. mtDNA sequencing of multiple sections from two different long bones yielded compiled results consistent with either Haplogroup H or R, both predominantly European mtDNA haplogroups. Further anthropological calculations were conducted using cranial measurements, FORDISC™ software, and discriminant function analysis. Two-way, four-way, and multigroup discriminant function analyses further classify this set of unidentified remains as being White (European) in origin, with posterior probabilities of 0.999, 0.881 and 0.986, respectively. Combined with historical records of Sieur de Marle’s death, as well as overlays of historical and contemporary maps which demonstrate that the plantation site aligns with Joutel’s diary accounts of de Marle’s burial, these collective results support that these remains are of a European male and may possibly belong to this prominent member of La Salle’s expedition team.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background Shock‐reduction implantable cardioverter‐defibrillator programming (SRP) was associated with fewer therapies and improved survival in randomized controlled trials, but real‐world studies ...investigating SRP and associated outcomes are limited. Methods and Results The BIOTRONIK CERTITUDE registry was linked with the Medicare database. We included all patients with an implantable cardioverter‐defibrillator implanted between August 22, 2012 and September 30, 2021 in the United States. SRP was defined as programming to either a therapy rate cutoff ≥188 beats per minute or number of intervals to detection ≥30/40 for treatment. Among 6781 patients (mean 74±9 years; 27% women), 3393 (50%) had SRP. Older age, secondary prevention indication, and device implantation in the southern or western United States were associated with lower use of SRP. The cumulative incidence rate of implantable cardioverter‐defibrillator shocks was lower in the SRP group (5.1% shocks/patient year) compared with the non‐SRP group (7.2% shocks/patient year) (adjusted hazard ratio HR, 0.83 95% CI, 0.73–0.96; P =0.005). Over a median follow‐up of 2.9 years, 739 deaths occurred in the SRP group and 822 deaths occurred in the non‐SRP group (adjusted HR, 0.97 95% CI, 0.88–1.07; P =0.569). SRP was associated with a lower all‐cause mortality among patients without ischemic heart disease compared with patients with ischemic heart disease (adjusted HR, 0.64 95% CI, 0.48–0.87 versus adjusted HR, 1.02 95% CI, 0.92–1.14; P interaction =0.004). Conclusions Adoption of SRP is low in real‐world clinical practice. Age, clinical variables, and geographic factors are associated with use of SRP. In this study, SRP‐associated decrease in mortality was limited to patients without ischemic heart disease.
We describe measurements aimed at tracking the subsurface energy deposition of ionic radiation by encapsulating an irradiated oxide target within multiple, spatially separated ...metal–oxide–semiconductor (MOS) capacitors. In particular, we look at incident kinetic energy and potential energy effects in the low keV regime for alkali ions (Na+) and multicharged ions (MCIs) of Ar
Q+ (Q = 1, 4, 8, and 11) incident on the as-grown layers of SiO2 on Si. With the irradiated oxide encapsulated under Al top contacts, we record an electronic signature of the incident ionic radiation through capacitance–voltage (C–V) measurements. Both kinetic and potential energy depositions give rise to shifted C–V signatures that can be directly related to internal electron–hole pair excitations. The MCI data reveal an apparent power law dependence on charge state, which is at odds with some prior thin foil studies obtained at higher incident energies.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The Hebrew text of the OT names 27 rocks, minerals, and other materials that have been identified as gemstones in translations. These are mentioned most notably in the descriptionsof the high ...priest's breastplate (Exod 28:17–20 and 39:10–13 36:17–20 LXX) and the prince of Tyre's canopy (Ezek 28:13), but they are also found in dozens of other passages. Thisstudy attempts to identify these materials following a multidisciplinary approach that includes linguistic analysis (examining etymologies and descriptions of the stones),archaeological evidence (looking at the gemstones actually used in the Near East during the Late Bronze and Iron Ages as well as the ancient mines that may have supplied them), andgeological evidence (combining mineralogical and petrological data with knowledge of known gemstone deposits in the region). One or two possible identities are proposed for eachthe 27 materials, most of which are true gemstones.
We report on a measurement of low energy ion irradiation effects on as-grown films of SiO2 on a Si substrate. Beams of normally incident Na + ions with kinetic energies of 2 keV to 5 keV were focused ...onto ~ 1900 Å SiO2 films. Aluminum top metal contacts were subsequently deposited onto these targets such that irradiated regions and unexposed (pristine) regions of the target could be compared using capacitance-voltage (C-V) measurements of individual metal-oxide-semiconductor (MOS) devices. The C-V data reveal an energy-dependent shift in the flatband voltage ( VFB) that can be returned to its near-pristine value by a low temperature anneal. An increase in the density of interface states ( Dit) inferred from the C-V curves is found to have a superlinear dependence on the incident kinetic energy. These data are consistent with previously observed UV radiation effects on MOS oxides, where transferred energy leads to electron-hole pair production and the diffusion and trapping of holes throughout the oxide. Our measured trapped hole densities are compared with calculated densities, which are based on the incident ion dose and the predicted ion implantation range, to arrive at a fractional yield for hole survival and measurement within an encapsulated MOS device.
Elucidating how serine/threonine phosphatases regulate kinase function and bacterial virulence is critical for our ability to combat these infections. Group B streptococci (GBS) are β-hemolytic ...Gram-positive bacteria that cause invasive infections in humans. To adapt to environmental changes, GBS encodes signaling mechanisms comprising two component systems and eukaryotic-like enzymes. We have previously described the importance of the serine/threonine kinase Stk1 to GBS pathogenesis. However, how the presence or absence of the cognate serine/threonine phosphatase Stp1 affects Stk1 function and GBS virulence is not known. Here, we show that GBS deficient only in Stp1 expression are markedly reduced for their ability to cause systemic infections, exhibit decreased β-hemolysin/cytolysin activity, and show increased sensitivity to autolysis. Although transcription of genes important for β-hemolysin/cytolysin expression and export is similar to the wild type (WT), 294 genes (excluding stp1) showed altered expression in the stp1 mutant and included autolysin genes. Furthermore, phosphopeptide enrichment analysis identified that 35 serine/threonine phosphopeptides, corresponding to 27 proteins, were unique to the stp1 mutant. This included phosphorylation of ATP synthase, DNA and RNA helicases, and proteins important for cell division and protein synthesis. Collectively, our results indicate that Stp1 is important for appropriate regulation of Stk1 function, hemolysin activity, autolysis, and GBS virulence.
Background: Signaling mediated by serine/threonine phosphatases during bacterial pathogenesis is not completely understood.
Results: In Group B Streptococcus (GBS), Stp1 controls serine/threonine kinase function, post-transcriptional regulation of hemolysin, autolysis, and virulence.
Conclusion: Although not essential for growth, Stp1 is critical for GBS pathogenesis.
Significance: The importance of Stp1 in virulence and autolysis accentuates the possibility of using phosphatase inhibitors to decrease GBS infections.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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