An eighth-century inscribed cross-slab in Dull, Perthshire

The discovery of a cross-inscribed slab with an inscription is described. Because of its importance it was decided to invite specialist comment on this piece of sculpture and to publish it in advance of the full report on the excavations. The form of the monument, its inscription and archaeological context are considered. The text appears to consist of a Gaelic personal name. The script is a form of geometrical lettering which can be dated to the opening quarter of the eighth century. The form of the cross has Columban associations which sit well with place-name and other evidence which points to Dull having been a monastery founded from Iona by c. AD 700

Among-site variability in the stochastic dynamics of East African coral reefs

Coral reefs are dynamic systems whose composition is highly influenced by unpredictable biotic and abiotic factors. Understanding the spatial scale at which long-term predictions of reef composition can be made will be crucial for guiding conservation efforts. Using a 22-year time series of benthic composition data from 20 reefs on the Kenyan and Tanzanian coast, we studied the long-term behaviour of Bayesian vector autoregressive state-space models for reef dynamics, incorporating among-site variability. We estimate that if there were no among-site variability, the total long-term variability would be approximately one third of its current value. Thus among-site variability contributes more to long-term variability in reef composition than does temporal variability. Individual sites are more predictable than previously thought, and predictions based on current snapshots are informative about long-term properties. Our approach allowed us to identify a subset of possible climate refugia sites with high conservation value, where the long-term probability of coral cover <= 0.1 was very low. Analytical results show that this probability is most strongly influenced by among-site variability and by interactions among benthic components within sites. These findings suggest that conservation initiatives might be successful at the site scale as well as the regional scale.Comment: 97 pages, 49 figure

A New Class of non-Hermitian Quantum Hamiltonians with PT Symmetry

In a remarkable development Bender and coworkers have shown that it is possible to formulate quantum mechanics consistently even if the Hamiltonian and other observables are not Hermitian. Their formulation, dubbed PT quantum mechanics, replaces hermiticity by another set of requirements, notably that the Hamiltonian should be invariant under the discrete symmetry PT, where P denotes parity and T denotes time reversal. All prior work has focused on the case that time reversal is even (T^2 = 1). We generalize the formalism to the case of odd time reversal (T^2 = -1). We discover an analogue of Kramer's theorem for PT quantum mechanics, present a prototypical example of a PT quantum system with odd time reversal, and discuss potential applications of the formalism. Odd time reversal symmetry applies to fermionic systems including quarks and leptons and a plethora of models in nuclear, atomic and condensed matter physics. PT quantum mechanics makes it possible to enlarge the set of possible Hamiltonians that physicists could deploy to describe fundamental physics beyond the standard model or for the effective description of condensed matter phenomena.Comment: Replaced submitted version with accepted version; to appear in Phys Rev

6'-Methoxy Raloxifene-analog enhances mouse bone properties with reduced estrogen receptor binding

Raloxifene (RAL) is an FDA-approved drug used to treat osteoporosis in postmenopausal women. RAL suppresses bone loss primarily through its role as a selective estrogen receptor modulator (SERM). This hormonal estrogen therapy promotes unintended side effects, such as hot flashes and increased thrombosis risk, and prevents the drug from being used in some patient populations at-risk for fracture, including children with bone disorders. It has recently been demonstrated that RAL can have significant positive effects on overall bone mechanical properties by binding to collagen and increasing bone tissue hydration in a cell-independent manner. A Raloxifene-Analog (RAL-A) was synthesized by replacing the 6-hydroxyl substituent with 6-methoxy in effort to reduce the compound's binding affinity for estrogen receptors (ER) while maintaining its collagen-binding ability. It was hypothesized that RAL-A would improve the mechanical integrity of bone in a manner similar to RAL, but with reduced estrogen receptor binding. Molecular assessment showed that while RAL-A did reduce ER binding, downstream ER signaling was not completely abolished. In-vitro, RAL-A performed similarly to RAL and had an identical concentration threshold on osteocyte cell proliferation, differentiation, and function. To assess treatment effect in-vivo, wildtype (WT) and heterozygous (OIM+/-) female mice from the Osteogenesis Imperfecta (OI) murine model were treated with either RAL or RAL-A from 8 weeks to 16 weeks of age. There was an untreated control group for each genotype as well. Bone microarchitecture was assessed using microCT, and mechanical behavior was assessed using 3-point bending. Results indicate that both compounds produced analogous gains in tibial trabecular and cortical microarchitecture. While WT mechanical properties were not drastically altered with either treatment, OIM+/- mechanical properties were significantly enhanced, most notably, in post-yield properties including bone toughness. This proof-of-concept study shows promising results and warrants the exploration of additional analog iterations to further reduce ER binding and improve fracture resistance

Lexical organization in deaf children who use British Sign Language: Evidence from a semantic fluency task

We adapted the semantic fluency task into British Sign Language (BSL). In Study 1, we present data from twenty-two deaf signers aged four to fifteen. We show that the same ‘cognitive signatures’ that characterize this task in spoken languages are also present in deaf children, for example, the semantic clustering of responses. In Study 2, we present data from thirteen deaf children with Specific Language Impairment (SLI) in BSL, in comparison to a subset of children from Study 1 matched for age and BSL exposure. The two groups' results were comparable in most respects. However, the group with SLI made occasional word-finding errors and gave fewer responses in the first 15 seconds. We conclude that deaf children with SLI do not differ from their controls in terms of the semantic organization of the BSL lexicon, but that they access signs less efficiently

Positive impact of low-dose, high-energy radiation on bone in partial- and/or full-weightbearing mice

Astronauts traveling beyond low Earth orbit will be exposed to galactic cosmic radiation (GCR); understanding how high energy ionizing radiation modifies the bone response to mechanical unloading is important to assuring crew health. To investigate this, we exposed 4-mo-old female Balb/cBYJ mice to an acute space-relevant dose of 0.5 Gy 56Fe or sham (n = ~8/group); 4 days later, half of the mice were also subjected to a ground-based analog for 1/6 g (partial weightbearing) (G/6) for 21 days. Microcomputed tomography (µ-CT) of the distal femur reveals that 56Fe exposure resulted in 65-78% greater volume and improved microarchitecture of cancellous bone after 21 d compared to sham controls. Radiation also leads to significant increases in three measures of energy absorption at the mid-shaft femur and an increase in stiffness of the L4 vertebra. No significant effects of radiation on bone formation indices are detected; however, G/6 leads to reduced % mineralizing surface on the inner mid-tibial bone surface. In separate groups allowed 21 days of weightbearing recovery from G/6 and/or 56Fe exposure, radiation-exposed mice still exhibit greater bone mass and improved microarchitecture vs. sham control. However, femoral bone energy absorption values are no longer higher in the 56Fe-exposed WB mice vs. sham controls. We provide evidence for persistent positive impacts of high-LET radiation exposure preceding a period of full or partial weightbearing on bone mass and microarchitecture in the distal femur and, for full weightbearing mice only and more transiently, cortical bone energy absorption values

Are school-level factors associated with primary school students' experience of physical violence from school staff in Uganda?

BACKGROUND: The nature and structure of the school environment has the potential to shape children's health and well being. Few studies have explored the importance of school-level factors in explaining a child's likelihood of experiencing violence from school staff, particularly in low-resource settings such as Uganda. METHODS: To quantify to what extent a student's risk of violence is determined by school-level factors we fitted multilevel logistic regression models to investigate associations and present between-school variance partition coefficients. School structural factors, academic and supportive environment are explored. RESULTS: 53% of students reported physical violence from staff. Only 6% of variation in students' experience of violence was due to differences between schools and half the variation was explained by the school-level factors modelled. Schools with a higher proportion of girls are associated with increased odds of physical violence from staff. Students in schools with a high level of student perceptions of school connectedness have a 36% reduced odds of experiencing physical violence from staff, but no other school-level factor was significantly associated. CONCLUSION: Our findings suggest that physical violence by school staff is widespread across different types of schools in this setting, but interventions that improve students' school connectedness should be considered

Family Tensions and Information Privacy: A Barrier to Diffusion of Proximity Tracing Applications?

Technology played a central role during the pandemic for communications and services. It was also touted as a potential solution to control the spread of COVID-19 via proximity tracing applications, also known as contact tracing (CT) apps worldwide. In non-mandated settings, however, these apps did not attain popularity. Privacy concerns were highlighted as one reason. We explored how family perceptions of CT apps can affect the family’s use of such apps. We surveyed parent-teen dyads twice over a 5-month period. We analyzed parent-teen perceptions of each other’s intentions and use of CT apps at time 1 and 2, exploring changes over time. Parents’ use intentions were influenced by their and their teens’ perceptions of the benefits but not privacy concerns. Teen intentions were influenced by their own perceptions of benefits, not their parent’s, and their parent’s concerns for the family. Intentions always influenced usage, including intentions at time 1 influencing use at time 2, demonstrating a longitudinal effect of intentions on usage existed for parents and teens

Phase 1 study of sirolimus in combination with oral cyclophosphamide and topotecan in children and young adults with relapsed and refractory solid tumors.

PurposeTo determine the maximum tolerated dose (MTD), toxicities, and pharmacodynamics effects of sirolimus combined with oral metronomic topotecan and cyclophosphamide in a pediatric population.Materials and methodsPatients who were 1 to 30 years of age with relapsed/refractory solid tumors (including CNS) were eligible. Patients received daily oral sirolimus and cyclophosphamide (25-50 mg/m2/dose) on days 1-21 and oral topotecan (0.8 mg/m2/dose) on days 1-14 in 28-day cycles. Sirolimus steady-state plasma trough concentrations of 3-7.9 ng/mL and 8-12.0 ng/mL were evaluated, with dose escalation based on a 3+3 phase 1 design. Biomarkers of angiogenesis were also evaluated.ResultsTwenty-one patients were treated (median age 18 years; range 9-30). Dose-limiting toxicities included myelosuppression, ALT elevation, stomatitis, and hypertriglyceridemia. The MTD was sirolimus with trough goal of 8-12.0 ng/mL; cyclophosphamide 25 mg/m2/dose; and topotecan 0.8 mg/m2/dose. No objective responses were observed. Four patients had prolonged stable disease &gt; 4 cycles (range 4-12). Correlative biomarker analyses demonstrated reductions in thrombospondin-1 (p=0.043) and soluble vascular endothelial growth factor receptor-2 plasma concentrations at 21 days compared to baseline.ConclusionsThe combination of oral sirolimus, topotecan, and cyclophosphamide was well tolerated and biomarker studies demonstrated modulation of angiogenic pathways with this regimen