Short Mean Research Articles

Measurable progression of giant cell tumour of bone associated with pregnancy - A tertiary sarcoma centre analysis

IntroductionGiant cell tumour of bone (GCTB) is a benign but locally aggressive bone tumour with a higher predilection for females of reproductive age. GCTB management poses a unique set of challenges during pregnancy due to risks associated with imaging and treatment options. Pregnancy has been implicated in GCTB progression and tumour recurrence, however an exact mechanism has not been established. This study aims to confirm the relationship between the diagnosis and progression of GCTB during pregnancy. MethodsA 17-year retrospective analysis of our tertiary sarcoma referral centre database was performed to identify the relevant patients. Pregnancy-associated tumours were defined by those already present or diagnosed during pregnancy, and up to 12 months postpartum. Lesion volume was determined by mathematical ellipsoidal modelling technique to simplify the estimation, with cross-sectional measurements obtained from the three standard orthogonal planes on initial and surveillance imaging. Due to logistical challenges, follow-up imaging was performed at either our tertiary sarcoma centre or under guidance at regional imaging centres convenient to the patient. ResultsThe diagnosis of GCTB was made in 113 female patients during this 17-year period, of which 20 were associated with pregnancy with a mean age of 28.8 years (range 19–40 years). 12 patients had their primary or recurrent GCTB diagnosed, or known tumour progress during pregnancy, whilst the remaining 8 were diagnosed shortly thereafter to within 12 months postpartum. The most common tumour sites were located around the knee (30 %) and distal radius (25 %). A statistically significant pattern of growth was observed through the surveillance period (p 0.018), within a relatively short mean follow-up period of only 89.8 days (SD 54.5; 13–192 days). ConclusionThis study demonstrates the significant association that pregnancy has with the growth and progression of both primary and recurrent GCTB. Pregnant patients should be subject to close surveillance well into the postpartum period due to possible accelerated disease progression and potential for disease recurrence.

Total Knee Replacement Among Elderly: The Role of Tranexamic Acid.

Background Tranexamic acid (TXA) administration in total knee replacement (TKR) surgery has been shown to reduce blood loss and transfusion requirements. However, its efficacy and safety in elderly patients undergoing arthroplasty remain under investigation. This study aimed to assess the impact of TXA on blood loss and post-operative outcomes in TKR patients among a local elderly population. Methodology A prospective descriptive-analytical hospital-based randomized study was conducted, involving 79 TKR patients who received TXA. Demographic data, comorbidities, pre- and post-operative hemoglobin levels, length of hospital stay, transfusion requirements, and post-operative complications were recorded. Statistical analysis was performed using SPSS (IBM Corp., Armonk, NY), including descriptive analysis and comparative tests. Results The mean drop in hemoglobin levels post-operatively was -1.55 g/dL (SD = 0.94). The majority of patients (78, 98.7%) did not require packed red blood cell transfusions post-operatively, and complications were minimal (1, 1.3%). The length of hospital stay was relatively short (mean = 4.84 days). Comparison with existing literature revealed TXA's effectiveness in reducing blood loss compared to studies without TXA administration. Conclusion TXA administration in TKR surgery effectively reduced blood loss, transfusion requirements, and post-operative complications, supporting its use as a standard adjunctive therapy. These findings emphasize the importance of TXA in optimizing patient outcomes and minimizing surgical complications in TKR patients. Limitations of the study include the relatively small sample size and the exclusion of patients with certain comorbidities, which may limit the generalizability of the findings. Further research is warranted to validate these findings in larger patient cohorts and explore long-term effects.

How do intervals between fires influence canopy seed production and viability?

Abstract Canopy storage of seed (serotiny) is an important persistence strategy in fire‐prone environments. Serotinous populations can be threatened when fire intervals are shorter than the time needed to accumulate seed, or when longer than plant lifespans. Understanding how fire regimes influence canopy seedbanks requires study of the timing of plant maturity, seed output and germination traits. Research that spans plant functional types, such as resprouters or obligate seeders, helps to understand the mechanisms through which fire has influence. Using field data collected at 57 sites in a Mediterranean shrubland of southeastern Australia, we modelled how time since fire and mean fire interval influenced infructescence (hereby cone) production. Additionally, seed output, viability and germination speed were assessed in the laboratory. Reproductively mature resprouters were first observed 2 to 4 years post‐fire in the field, and reproductively mature obligate seeders 6 years post‐fire, depending on the species. Reproductively mature plants were not observed at short mean fire intervals: until 3 and 9 years for resprouters and nine and 18 years for obligate seeders, again, varying by species. When resprouter species reached maturity, we observed a decline in cone production as time since fire increased. This decline was not observed for obligate seeder species. Fire influenced the number of viable seeds produced within cones for one resprouter species, Allocasuarina paludosa, but we did not detect a relationship for other species. Germination speed was faster for species that produce few seeds per cone, and slower for species that produce many seeds, indicating a trade‐off between fire‐related seed traits. For example, Hakea rostrata, which holds two seeds per cone, germinated mostly within the first few weeks, while Callitris rhomboidea, which holds many seeds per cone, germinated asynchronously over 9 months. Short intervals between fires reduce canopy seed production for the serotinous species studied. Obligate seeders were more sensitive to frequent fire than resprouters. In the context of expected increases in wildfire frequency and droughts in Mediterranean ecosystems, our findings suggest that serotinous species' reproduction and recruitment will be differentially impacted depending on a suite of functional traits. Read the free Plain Language Summary for this article on the Journal blog.

Postdiscontinuation Antibiotic Exposure in Hospitalized Infants at Risk for Late-onset Sepsis in the Neonatal Intensive Care Unit.

In the neonatal intensive care unit, infants are at risk for late-onset sepsis. When blood cultures are negative, antibiotic stewardship efforts encourage stopping antibiotics, yet the duration of therapeutic exposure after the last dose is unknown. This retrospective cohort study of simulated antibiotic exposures used published population pharmacokinetic models within drug-specific neonatal intensive care unit cohorts of preterm and term infants, postnatal age 7-60 days and exposed to cefepime, piperacillin-tazobactam or tobramycin. Monte Carlo simulations (NONMEM 7.3) were used to predict steady-state exposures after a 72-hour antibiotic course per Neofax dosing. Exposure was assessed relative to drug-specific minimum inhibitory concentration (MIC) targets between 1 and 16 mcg/mL for Pseudomonas and Enterobacteriaceae species. Postdiscontinuation antibiotic exposure (PDAE) was defined as the time from the last dose to when antibiotic concentration decreased below a specific MIC. Piperacillin-tazobactam, cefepime and tobramycin cohorts included infants with median gestation age 29, 32 and 32 weeks and postnatal age 17, 19 and 15 days, respectively. The mean PDAE was 19-68 hours, depending on the specific antibiotic/MIC combination. PDAE was longer for infants <28 days old and preterm (vs. term) infants. Cefepime exhibited the longest mean PDAE of 68 hours for Enterobacteriaceae MIC 1. Piperacillin mean PDAE was 25 hours for Enterobacteriaceae MIC 8. Tobramycin had a short mean PDAE of 19 hours. Piperacillin and cefepime exposures remained therapeutic long after the expected 8- to 12-hour dosing interval. PDAE is an important consideration for antibiotic stewardship among hospitalized infants, particularly premature infants and those within 1 month postbirth.

Increased coexpression of PD-L1 and IDO1 is associated with poor overall survival in patients with NK/T-cell lymphoma.

Immunotherapy with programmed cell death 1 ligand 1 (PD-L1) blockade was effective in patients with NK/T-cell lymphoma. In addition to PD-L1, indoleamine 2,3-dioxygenase-1 (IDO1) is one of the most promising immunotherapeutic targets. High proportions of PD-L1 and IDO1 proteins were observed by immunohistochemistry (IHC) from 230 newly diagnosed patients with NK/T lymphoma with tissue samples from three cancer centers and were associated with poor overall survival (OS) in patients with NK/T lymphoma. Importantly, the coexpression of PD-L1 and IDO1 was related to poor OS and short restricted mean survival time in patients with NK/T lymphoma and was an independent prognostic factor in the training cohorts, and which was also validated in 58 NK/T lymphoma patients (GSE90597). Moreover, a nomogram model constructed with PD-L1 and IDO1 expression together with age could provide concise and precise predictions of OS rates and median survival time. The high-risk group in the nomogram model had a positive correlation with CD4 + T-cell infiltration in the validation cohort, as did the immunosuppressive factor level. Therefore, high PD-L1 and IDO1 expression was associated with poor OS in patients with NK/T lymphoma. PD-L1 and IDO1 might be potential targets for future immune checkpoint blockade (ICB) therapy for NK/T lymphoma.

Parallel expansion of a fuel pellet plasmoid

The problem of the assimilation of a cryogenic fuel pellet injected into a hot plasma is considered. Due to the transparency to ambient particles of the plasmoid, the localised region of high-density plasma created by ionisation of the ablated pellet material, electrons reach a ‘quasiequilibrium’ (QE) state which is characterised by a steady-state on the fastest collisional time scale. The simplified electron kinetic equation of the QE state is solved. Taking a velocity moment of the higher-order electron kinetic equation, which is valid on the expansion time scale, permits a fluid closure, yielding an evolution equation for the macroscopic parameters describing the QE distribution function. In contrast to the Braginskii equations, the closure does not require that electrons have a short mean free path compared with the size of density perturbations, and permits an anisotropic and highly non-Maxwellian distribution function. As the QE distribution function accounts for both trapped and passing electrons, the self-consistent electric potential that causes the expansion can be properly described, in contrast to earlier models of pellet plasmoid expansion with an unbounded potential. The plasmoid expansion is simulated using both a Vlasov model and a cold-fluid model for the ions. During the expansion plasmoid ions and electrons obtain nearly equal amounts of energy; as hot ambient electrons provide this energy in the form of collisional heating of plasmoid electrons, the expansion of a pellet plasmoid is expected to be a potent mechanism for the transfer of energy from electrons to ions on a time scale shorter than that of ion–electron thermalisation.

Synergistic role of Sn-doping on the thermal and electrical properties of sinnerite Cu6As4S9

Sinnerite Cu6As4S9 has been identified as a promising material for optoelectronic applications, with potential for other energy-related applications; however, knowledge of the electrical and thermal properties as well as the mechanisms underlying transport in sinnerite is lacking. We present an investigation of the synthesis, structural, thermal and electrical transport properties of stoichiometric and Sn-doped Cu6As4S9. Sinnerite has a triclinic lattice structure, with highly distorted local atomic coordination environments that, in part, results in its complex structure and bonding. Our results and analyses indicate As 4s2 lone pair-induced distortions and strong lattice anharmonicity that leads to a relatively short phonon mean free path, resulting in intrinsically very low thermal conductivity. The electrical resistivity for both compositions, Cu6As4-xSnxS9 (x = 0, 0.2), are relatively high and varies little with temperature, typical of degenerate semiconductors. An increase in mobility and electrical conductivity was obtained by Sn doping in Cu6As3.8Sn0.2S9. This work demonstrates an effective route to synthesize bulk sinnerite as well as advances the knowledge of the properties of sinnerite, as this and other ternary chalcogenides continue to be of interest for potential technologically significant applications.

RuAl intermetallic compound of low resistivity scaling and high thermal stability as potential interconnect metallization

Thin films of single-phase ruthenium aluminide (RuAl) intermetallic compound were deposited by magnetron co-sputtering. An ordered B2 body-centered cubic structure of high crystallinity was formed after rapid thermal annealing at 800 °C for 1 min. Data fittings using the Fuchs–Sondheimer and Mayadas–Shatzkes models suggested the very short mean free path of electrons of below 5 nm and the high specularity parameter of 0.9. The short mean free path and the much reduced diffuse scattering of electrons at the interface effectively suppressed the resistivity scaling of the B2 RuAl intermetallic compound as compared to ruthenium metal. At an ultra-small film thickness of below 5 nm, the reflection of electrons by grain boundaries or domain walls might alternatively dominate the increase in resistivity. The RuAl intermetallic compound with an ordered B2 structure and a high cohesive energy (a large negative mixing enthalpy) also demonstrated a superior thermal stability at an extreme temperature up to 900 °C. It could be a promising candidate for potential use as the next-generation interconnect metallization without the need of a diffusion barrier.

Constraints on the Evolution of the Ionizing Background and Ionizing Photon Mean Free Path at the End of Reionization

The variations in Lyα forest opacity observed at z > 5.3 between lines of sight to different background quasars are too strong to be caused by fluctuations in the density field alone. The leading hypothesis for the cause of this excess variance is a late, ongoing reionization process at redshifts below six. Another model proposes strong ionizing background fluctuations coupled to a short, spatially varying mean free path of ionizing photons, without explicitly invoking incomplete reionization. With recent observations suggesting a short mean free path at z ∼ 6, and a dramatic improvement in z > 5 Lyα forest data quality, we revisit this latter possibility. Here, we apply the likelihood-free inference technique of approximate Bayesian computation (ABC) to jointly constrain the hydrogen photoionization rate ΓHI and the mean free path of ionizing photons λ mfp from the effective optical depth distributions at z = 5.0–6.1 from XQR-30. We find that the observations are well-described by fluctuating mean free path models with average mean free paths that are consistent with the steep trend implied by independent measurements at z ∼ 5–6, with a concomitant rapid evolution of the photoionization rate.

Top-down control of climate on long-term interactions between fires, tree-cover and soil erosion in a Mediterranean mountain, Corsica

Fire is a potential significant driver of soil erosion in the Mediterranean area, as it results in the partial removal of vegetation and the alteration of organic matter, affecting soil structure and stability. The erosion of particle sizes is influenced by the intensity and duration of rainfall, regulated by disturbance regimes and vegetation cover. We hypothesize that, during the Holocene, high fire frequency and intensity under precipitation control may have contributed to soil erosion, while plant cover and composition could have mitigated it. This plant cover, in turn, might have been influenced by biomass burning. To test this hypothesis, we conducted a detailed analysis of sediments spanning the last 11,500 years from a small mountain lake, Corsica, situated in the black pine forest belt. The high temporal resolution analysis (∼10 years per sample), used granulometry and loss-on-ignition as proxies for erosion and ecosystem productivity in both the lake and watershed, and fire and plant macroremains as fire and tree cover proxies, respectively. The correlation between particle size and the contents of organic or mineral matter with mean fire return intervals (FRI) revealed significant patterns. Long fire intervals were associated with more fine and coarse sands, whereas short mean FRI positively correlated with clay and, fine and coarse silt, along with higher total mineral and organic matter contents. These findings suggest that fires were more frequent when rain duration was sustained but runoff intensity was lower. Conversely, wildfires were less frequent during intense runoff periods (wetter climate). Unlike fire frequency, fire severity did not correlate with erosion, and tree cover and plant richness had minimal to no effect. The 8.2 kyr event was characterized by runoff transporting primarily coarse sands, i.e. a dry period with very intense rains. This suggests that the system is primarily top-down controlled by climate. Multimillennial erosion trends are influenced by fire frequency and precipitation regimes, whereas vegetation does not seem to have a mitigating effect on this process.

Pengembangan Bahan Ajar Digital Berbasis Articulate Storyline pada Pembelajaran Teks Prosedur di Sekolah Menengah Atas

&lt;p&gt;&lt;em&gt;Short learning hours mean that learning cannot be carried out effectively. Learning materials that cannot be conveyed well will affect students' understanding, so they require teaching materials that students can study independently and can be accessed at any time. Teaching materials are generally used as learning tools that contain learning materials for a teacher to use in delivering learning. This research aims to develop articulate storyline-based digital teaching materials in the form of learning applications on procedural text material as an alternative for solving existing problems in class 11 Science 1 SMA Muhammadiyah 1 Pekanbaru. The method used in this research is R&amp;amp;D through the ADDIE approach. This research uses a Pre-Experimental Design, namely using only one experimental class without a control class with a One-Group Pretest-Posttest Design model. The research instruments used were questionnaires and pre-test and post-test essay questions. The result is that the average percentage of expert validation of products is 92% in the very good category, the average percentage of teacher assessments is 93% in the very good category, the average percentage of student assessments is 90% in the very good category. The research results can be concluded that there are differences in student learning outcomes between learning procedural texts without digital teaching materials in the form of learning applications using digital teaching materials based in the form of learning applications based on the Wilcoxon test of pretest and posttest data with Asymp values. Sig. (2-tailed) of 0.000 &amp;lt; 0.05&lt;/em&gt;&lt;/p&gt;

Explainable Learning-Based Timeout Optimization for Accurate and Efficient Elephant Flow Prediction in SDNs

Accurately and efficiently predicting elephant flows (elephants) is crucial for optimizing network performance and resource utilization. Current prediction approaches for software-defined networks (SDNs) typically rely on complete traffic and statistics moving from switches to controllers. This leads to an extra control channel bandwidth occupation and network delay. To address this issue, this paper proposes a prediction strategy based on incomplete traffic that is sampled by the timeouts for the installation or reactivation of flow entries. The strategy involves assigning a very short hard timeout (Tinitial) to flow entries and then increasing it at a rate of r until flows are identified as elephants or out of their lifespans. Predicted elephants are switched to an idle timeout of 5 s. Logistic regression is used to model elephants based on a complete dataset. Bayesian optimization is then used to tune the trained model Tinitial and r over the incomplete dataset. The process of feature selection, model learning, and optimization is explained. An extensive evaluation shows that the proposed approach can achieve over 90% generalization accuracy over 7 different datasets, including campus, backbone, and the Internet of Things (IoT). Elephants can be correctly predicted for about half of their lifetime. The proposed approach can significantly reduce the controller–switch interaction in campus and IoT networks, although packet completion approaches may need to be applied in networks with a short mean packet inter-arrival time.

An audit of the maternal medicine clinic: Cancer and pregnancy.

To explore the incidence and complexity of women presenting for maternity care who require concurrent cancer care, and to report the birth outcomes of these women. A retrospective audit of women attending a 'high risk' maternal medicine clinic at an Australian tertiary maternity hospital between 1 October 2021 and 30 April 2023 was conducted. The inclusion criteria were a diagnosis of cancer and a concurrent pregnancy, or a diagnosis of cancer prior to the current pregnancy. Clinic lists and coding data were screened via the electronic medical record to identify potential subjects. Data were collected from the individual maternity and neonatal records. Forty of 705 (5.7%) women attending the maternal medicine clinic met the inclusion criteria, of which ten had a new diagnosis of cancer in pregnancy and 30 presented for maternity care after a previous diagnosis of cancer. Cancer therapy during pregnancy included surgery and chemotherapy. Most pregnancies (92.5%) resulted in term deliveries (≥37 weeks gestation). Four neonates were preterm, and one was small-for-gestational-age. Caesarean section delivery and post-partum haemorrhage were more common than expected, but the rate of other adverse pregnancy outcomes was consistent with the background population. Over half of neonates required neonatal intensive care unit / special care nursery admission but the indications for admission were common, self-limiting conditions, and the length of stay was short (mean <5.0 days). Approximately 6% of women attending the maternal medicine clinic had a current or previous diagnosis of cancer. Most pregnancies resulted in term deliveries and neonatal outcomes were excellent.

Surface sulfurization of liner and ruthenium metallization to reduce interface scattering for Low-Resistance interconnect

Ruthenium with a low resistivity, high melting temperature and short electron mean free path has been considered to replace copper as the next-generation interconnect metallization. However, its ascending resistivity with linewidth scaling because of the diffuse scattering of electrons at the interface with dielectrics or liners is a concern. Thus, in this study, sulfurization was applied on the surface of titanium-tantalum nitride and ruthenium films to form an ultrathin sulfide layer to reduce interface scattering. The microstructure, chemical composition, bonding configuration, and stability of the layer were characterized, and the resistivity scaling of the ruthenium films was examined. Microscopic observations suggested a crystalline TiTaSx layer formed on the titanium-tantalum nitride films while RuS2 formed on the ruthenium films, both of which changed the binding state/energy of the metals. With the surface sulfurization, the interface scattering of electrons for the ruthenium films was effectively reduced to elevate the specularity parameter from 0.2 to 0.9 and lessen the resistivity scaling for at least 40 % at a thickness of below 10 nm, without a marked loss of interfacial adhesion. However, an increase in contact resistance of molybdenum to the surface-sulfurized ruthenium films needs to be considered.

Unveiling the ultralow in-plane thermal conductivity in 2D organic–inorganic hybrid perovskite (EA)2PbI4 single crystals

2D organic–inorganic hybrid perovskites EA2PbI4 exhibit ultralow in-plane thermal conductivity, approaching the amorphous limit, due to the exceptionally short phonon mean free paths comparable to the Pb–I bond lengths within the PbI6 octahedra.

Anharmonicity and lattice thermal conductivity of negative thermal expansion materials Zn(CN)2 and Cd(CN)2 by first-principles calculations.

Certain negative thermal expansion (NTE) materials have been reported to exhibit anomalous lattice thermal conductivity (LTC), making them particularly interesting for theoretical studies. In Zn(CN)2 and Cd(CN)2, cyanide bonds have induced great NTE behavior and anharmonicity, making us believe they would exhibit anomalous LTC. To investigate this, we employed first-principles calculations based on density functional theory and solved the linearized Boltzmann transport equation within the relaxation time approximation to calculate the LTC. Our analysis reveals that both Zn(CN)2 and Cd(CN)2 have low LTC, with Cd(CN)2 exhibiting a notably anomalous glass-like behavior. Some phonons with long lifetimes, short mean free paths (MFPs), and strong anharmonicity contribute most to the anomalous LTC observed in both materials. Analysis of the phonon spectral functions and the weighted joint density of states reveals that three-phonon interactions are significant in both materials, impacting their LTCs, particularly in Cd(CN)2.

Low-dimensional heat conduction in surface phonon polariton waveguide

Heat conduction in solids is typically governed by the Fourier’s law describing a diffusion process due to the short wavelength and mean free path for phonons and electrons. Surface phonon polaritons couple thermal photons and optical phonons at the surface of polar dielectrics, possessing much longer wavelength and propagation length, representing an excellent candidate to support extraordinary heat transfer. Here, we realize clear observation of thermal conductivity mediated by surface phonon polaritons in SiO2 nanoribbon waveguides of 20-50 nm thick and 1-10 μm wide and also show non-Fourier behavior in over 50-100 μm distance at room and high temperature. This is enabled by rational design of the waveguide to control the mode size of the surface phonon polaritons and its efficient coupling to thermal reservoirs. Our work laid the foundation for manipulating heat conduction beyond the traditional limit via surface phonon polaritons waves in solids.

Regional amyloid‐β is linked to disruptions in connected speech in amnestic mild cognitive impairment

AbstractBackgroundSpeech changes in amnesic mild cognitive impairment (aMCI) are potential markers for the early detection of Alzheimer disease (AD). However, few studies investigate the relationship between speech and amyloid‐β burden. The focus of this study was to examine the relationship between the linguistic features and the distribution of amyloid‐β load in aMCI.MethodThis study recruited 25 aMCI patients (52% female, aged 70‐85 years) and 25 healthy elders (44% female, aged 68‐80 years) from the memory clinic of Cardinal Tian Hospital in Taiwan. All participants received [18F] florbetaben PET and standardized cognitive tests. Amyloid‐β load using a standardized uptake value ratio (SUVr) was estimated from 5 cortical regions (parietal, frontal, cingulate, temporal, and occipital). Spontaneous speech was recorded using the picture description task (three Taiwanese culture‐related pictures) and transcribed verbatim. Linguistic features were extracted, including lexical richness (total words, unique words, type‐token‐ratio, lexical density, and frequency), syntactic complexity (mean length of utterance/sentence, ratio of verbs/pronouns/passive sentence), and speech fluency (ratio of long pauses/ fillers).ResultEighteen subjects with high amyloid burden (SUVr &gt; 1.21) progressed (defined as CDR‐SB change≧1) within 1 year. We performed linear regression analyses between linguistic features (dependent variables, separate models) and amyloid‐β load in brain regions. Analyses were adjusted for age and education. The data revealed that a high amyloid‐β burden in the frontal region was associated with fewer unique words, less lexical density, and an increased proportion of long pauses and fillers. Reduced passive sentence, short mean length of utterance and lower scores on episodic memory tests related to increased amyloid‐β burden in the parietal region.ConclusionLexical richness and speech fluency was associated with amyloid‐β burden in the frontal region, indicating that voluntary lexical retrieval may require the additional recruitment of frontal lobe. Less syntactic complexity related to increased amyloid‐β burden in the parietal region. In conclusion, regional amyloid‐β is linked to subtle spontaneous speech deficits in aMCI.

Germline Variant in ZCCHC8 Is Associated with Pulmonary Fibrosis, Bone Marrow Failure, Liver Inflammation, Early Grey Hair and Short Telomer Length

Introduction Telomere biology disorders (TBD) encompass rare genetic conditions that affect telomere function. TBD is associated with a wide range of symptoms, including hematologic, dermatologic, pulmonary, hepatic manifestations. Research is continuously identifying novel variants and genes causative of TBD. In a recent study, Gable et al. (2019) detected a germline missense variant in ZCCHC8 (NM_017612.5:c.557C&amp;gt;T; p.(Pro186Leu)) in a single family with pulmonary fibrosis. This ZCCHC8 variant was associated with short telomere length (TL) and pulmonary fibrosis. To the best of our knowledge, no other families or individuals have been reported to have pathogenic variants in ZCCHC8 and TBD . However, in this abstract, we present data from a second family discovered to harbor a pathogenic variant in ZCCHC8 and to have symptoms of TBD. Methods Family members provided informed consent for genetic testing and underwent trio-based whole-genome sequencing (WGS). DNA isolated from fkin-derived fibroblasts was analyzed in the proband, while DNA from whole blood was used for the parents. To measure TL, we employed Computel (Nersisyan L. et al., 2015) and compared the mean TL to a cohort of patients who also underwent WGS to estimate a relative mean TL. Results: The proband was a 14-year-old male who had pancytopenia and elevated ALAT levels at presentation. A bone marrow biopsy showed a hypocellular bone marrow. A liver biopsy revealed mild centrilobular, pericellular, and portal fibrosis, along with mild inflammation in the portal space, these findings were interpreted as liver regeneration following acute hepatitis. Despite thorough investigations, no explanation for the findings was found. The proband had a history of psychogenic non-epileptic seizures. When the patient was around 20 years of age his hair started to gray. At present, the proband is 23 years old and has not experienced any progression of symptoms. Family history revealed that the proband's father and two second-degree relatives on the paternal side of the family had developed pulmonary fibrosis in the fifth and sixth decade of life as well as early grey hair. Thus, the inheritance pattern of disease related to TBD was autosomal dominant. WGS revealed a heterozygous pathogenic variant in ZCCHC8 (NM_017612.5c.557C&amp;gt;T (p.P186L)) present in the proband and the father which was absent in the mother. The variant was the same as reported by Gable et al. (2019). The variant is not present in gnomAD or COSMIC and it is the only reported pathogenic or likely pathogenic ZCCHC8 missense variant in ClinVar to date. Both the proband and the father exhibited short relative mean TL by Computel estimation. Subsequently, Flow-FISH analysis confirmed that the proband's telomere length was below the 1st percentile. Conclusion Here we present a family with a heterozygous germline variant in ZCCHC8 and TBD including pulmonary fibrosis, pancytopenia, early graying of the hair, and liver disease. Thus, we provide strong evidence of an association between TBD and ZCCHC8.

Time and temperature abuse of milk in conditions representing a school cafeteria share table does not meaningfully reduce microbial quality

Share tables (ST) are tables or stations in school cafeterias where students can return unopened foods and beverages, providing an opportunity to access these items at no cost. Currently, research suggests that milk is among the most wasted items in breakfast and lunch programs in the United States. Share tables present a simple solution for reducing milk waste, but research is needed to understand the microbial spoilage potential of milk in ST. To this end, uninoculated milk cartons and milk cartons inoculated with 2 to 3 log10(cfu/mL) Pseudomonas poae, a fast-growing psychrotroph, was exposed to ambient temperature during winter (mean temperature = 20.3°C) and summer (23.1°C) for 125 min, repeated over 5 d (the length of a school week). Microbial counts in the inoculated milk cartons increased linearly, exceeding the spoilage threshold of 6.0 log10(cfu/mL) after d 3 and after d 4 in the winter and summer season trials, respectively. In the winter trial, the microbial counts for uninoculated milk cartons never exceeded the lower limit of detection, 2.31 log10(cfu/mL), and in the summer trials, microbial counts never reached the spoilage threshold, indicating that initial contamination is a driving factor of microbial milk spoilage. Regardless of sharing status or seasonality, the greatest changes in counts for inoculated milk cartons occurred during overnight refrigeration, ranging from 0.56 to 1.4 log10(cfu/mL), while during the share table ranged from no observable change up to 0.29 log10(cfu/mL), emphasizing that school nutrition personnel should focus efforts on tightly controlling refrigeration temperatures and returning milk to refrigeration as soon as possible. A previously developed model for school cafeteria share tables was adapted to understand the typical residence time of milk in a simulated cafeteria with an ambient temperature share table for the summer and winter seasons over 1,000 wk. Milk was predicted to have a very short mean residence time (85 min) regardless of sharing status or season, with 99.8% of milk consumed, discarded, or donated within the first 2 d. As a result, only 3 out of 451,410 and 6 out of 451,410 simulated milks spoiled in the winter and summer seasons, respectively. The data generated here can be used to inform science-based decision-making for including milk in share tables, or applied to any system where one might have to accept short-term unrefrigerated storage of milk to meet a waste reduction or food security goal.