Changes in Dry State Hemoglobin over Time Do Not Increase the Potential for Oxidative DNA Damage in Dried Blood

BACKGROUND: Hemoglobin (Hb) is the iron-containing oxygen transport protein present in the red blood cells of vertebrates. Ancient DNA and forensic scientists are particularly interested in Hb reactions in the dry state because both regularly encounter aged, dried bloodstains. The DNA in such stains may be oxidatively damaged and, in theory, may be deteriorated by the presence of Hb. To understand the nature of the oxidative systems potentially available to degrade DNA in the presence of dried Hb, we need to determine what molecular species Hb forms over time. These species will determine what type of iron (i.e. Fe(2+)/Fe(3+)/Fe(4+)) is available to participate in further chemical reactions. The availability of "free" iron will affect the ability of the system to undergo Fenton-type reactions which generate the highly reactive hydroxyl radical (OH*). The OH* can directly damage DNA. METHODOLOGY/PRINCIPAL FINDINGS: Oxygenated Hb (oxyHb) converts over time to oxidized Hb (metHb), but this happens more quickly in the dry state than in the hydrated state, as shown by monitoring stabilized oxyHb. In addition, dry state oxyHb converts into at least one other unknown species other than metHb. Although "free" iron was detectable as both Fe(2+) and Fe(3+) in dry and hydrated oxyHb and metHb, the amount of ions detected did not increase over time. There was no evidence that Hb becomes more prone to generating OH* as it ages in either the hydrated or dry states. CONCLUSIONS: The Hb molecule in the dried state undergoes oxidative changes and releases reactive Fe(II) cations. These changes, however, do not appear to increase the ability of Hb to act as a more aggressive Fenton reagent over time. Nevertheless, the presence of Hb in the vicinity of DNA in dried bloodstains creates the opportunity for OH*-induced oxidative damage to the deoxyribose sugar and the DNA nucleobases

Risks in circular business models innovation: A cross-industrial case study for composite materials

Circular business models (CBMs) are key enablers to implement circular economy (CE), yet they entail risks, which often discourage organisations. This work aims to explore the main risk factors perceived by the manufacturing industry in transitioning to CBMs to enable the development of appropriate risk management strategies. A cross- industrial multiple-case study research design was used to explore risk factors across seven organisations planning the transition to CBMs for composite-based products and involving three different CBM types—‘Circular Supplies’, ‘Product Life Extension’ and ‘Hybrid’. Results evidenced that risks are multi-disciplinary but are not equally per- ceived across different CBM types. Customers' perceptions of CE products, economic cycle and take-back systems were prevalent across all CBMs. Supply and technological risks were prioritised for ‘Circular Supplies’ CBM, whereas political and regulatory risks for ‘Product Life Extension’ CBM. This research contributes to the CE field by evaluating and prioritising the perceived risk factors in transitioning to CBMs and first disaggregating such risk factors according to CBM types. Critical risk patterns identified across different industries and CBM types enable mitigating actions to be prioritised

Sedimentary context and palaeoecology of Gigantoproductus shell beds in the Mississippian Eyam Limestone Formation, Derbyshire carbonate platform, central England

A sedimentological study was conducted at two localities exposing the Mississippian Eyam Limestone Formation of the Derbyshire carbonate platform, UK. Ricklow Quarry comprises seven facies with diverse skeletal assemblages, representing deposition on the inner to middle ramp within open marine waters. Once-a-Week Quarry comprises four facies, dominated by crinoidal debris representing deposition on the inner ramp. Both localities expose Gigantoproductus shell beds. Palaeoecological analysis of a single shell bed from each locality enabled investigation of the rapid colonization and success of this taxon on the platform. At Ricklow Quarry, on the eastern side of a localized mud mound, both life (>72% of thin and thick-shelled brachiopods in life position) and neighbourhood assemblages are present. A low-moderate diversity community (<1.37 and <0.8 Shannon diversity index) rapidly established over relict Brigantian mud mounds. Shell beds are preluded by intervals of decreased energy that allowed larvae to settle. Once established, the dominance of thick-shelled individuals enabled baffling, potentially providing localized shelter for larvae and nearby individuals. At Once-a-Week Quarry, where no mud mound is present, only thick-shelled Gigantoproductus species and a low diversity community (<1.07 Shannon diversity index) exclusively comprising neighbourhood assemblages (37% in life position) is present. The presence of inactive mud mounds at Ricklow Quarry appears to have been the key to the success of Gigantoproductus species enabling the onset of stable communities in the shelter provided by the relict mound. Once the first palaeocommunities were established, larvae dispersed and colonized higher energy settings, such as at Once-a-Week Quarry

Tests of amounts and times of application of nitrogen and of sequential sprays of aphicide and fungicides on winter wheat, following either beans or wheat, and the effects of take-all (Gaeumannomyces graminis var. tritici ), on two varieties at Saxmundham, Suffolk 1980-3

RESP-9258 and RESP-924

The diagnostic certainty levels of junior clinicians: A retrospective cohort study

BACKGROUND: Clinical decision-making is influenced by many factors, including clinicians' perceptions of the certainty around what is the best course of action to pursue. OBJECTIVE: To characterise the documentation of working diagnoses and the associated level of real-time certainty expressed by clinicians and to gauge patient opinion about the importance of research into clinician decision certainty. METHOD: This was a single-centre retrospective cohort study of non-consultant grade clinicians and their assessments of patients admitted from the emergency department between 01 March 2019 and 31 March 2019. De-identified electronic health record proformas were extracted that included the type of diagnosis documented and the certainty adjective used. Patient opinion was canvassed from a focus group. RESULTS: During the study period, 850 clerking proformas were analysed; 420 presented a single diagnosis, while 430 presented multiple diagnoses. Of the 420 single diagnoses, 67 (16%) were documented as either a symptom or physical sign and 16 (4%) were laboratory-result-defined diagnoses. No uncertainty was expressed in 309 (74%) of the diagnoses. Of 430 multiple diagnoses, uncertainty was expressed in 346 (80%) compared to 84 (20%) in which no uncertainty was expressed. The patient focus group were unanimous in their support of this research. CONCLUSION: The documentation of working diagnoses is highly variable among non-consultant grade clinicians. In nearly three quarters of assessments with single diagnoses, no element of uncertainty was implied or quantified. More uncertainty was expressed in multiple diagnoses than single diagnoses. IMPLICATIONS: Increased standardisation of documentation will help future studies to better analyse and quantify diagnostic certainty in both single and multiple working diagnoses. This could lead to subsequent examination of their association with important process or clinical outcome measures