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Biomagnification of mercury was investigated via combined mercury and stable isotope analysis of the blood and feathers of great skua chicks from two colonies in the north-east Atlantic. There were significant positive correlations between 15N signatures and mercury concentrations in the blood from chicks at both colonies suggesting that dietary specialization influences intra-specific variability in mercury burdens. The relationships were slightly weaker in feathers and therefore blood is probably a better monitoring unit. Adult blood was also assessed and in terms of biomonitoring may provide an index of mercury intake over the whole breeding season. [ABSTRACT FROM AUTHOR]

Synthetic small interfering RNAs conjugated to trivalent N -acetylgalactosamine (GalNAc) are clinically validated drugs for treatment of liver diseases. Incorporation of phosphorothioate linkages and ribose modifications are necessary for stability, potency, and duration of pharmacology. Although multiple alternative siRNA designs such as Dicer-substrate RNA, shRNA, and circular RNA have been evaluated in vitro and in preclinical studies with some success, clinical applications of these designs are limited as it is difficult to incorporate chemical modifications in these designs. An alternative siRNA design that can incorporate chemical modifications through straightforward synthesis without compromising potency will significantly advance the field. Here, we report a facile synthesis of GalNAc ligand-containing single-stranded loop hairpin RNAs (loopmeRNAs) with clinically relevant chemical modifications. We evaluated the efficiency of novel loopmeRNA designs in vivo and correlated their structure-activity relationship with the support of in vitro metabolism data. Sequences and chemical modifications in the loop region of the loopmeRNA design were optimized for maximal potency. Our studies demonstrate that loopmeRNAs can efficiently silence expression of target genes with comparable efficacy to conventional double-stranded siRNAs but reduced environmental and regulatory burdens.

The 2008 melamine crisis led to widespread consumer distrust of Chinese domestic infant milk formula (IMF), which was substituted through a surge of imported products. Recent studies, however, suggest a revival in consumer confidence in Chinese domestic products and regulatory supervision. This coincides with a rise in consumer ethnocentrism and increased concern about foreign IMF, which arose during the COVID-19 pandemic. This study aims to investigate the multifaceted factors that influence consumers' intention to purchase domestic IMF, using a structural equation model based on a survey of 563 online consumers. Our findings challenge conventional thinking that food safety governance, consumer ethnocentrism, and COVID-19 have no significant direct impact on IMF purchase decisions. Instead, consumer purchase intentions are driven more indirectly by mediating factors of perceived product quality and perceived behavioural control. The findings have significant implications for Chinese policymakers and industry stakeholders seeking to rebuild trust and strengthen the market position of domestic IMF in the post-melamine and post-pandemic era. By understanding the nuanced dynamics and consumer preferences in this market, international stakeholders can also develop more effective strategies to navigate and compete in the ever-evolving landscape of the Chinese IMF industry.

Research into defensive functioning in psychotherapy has thus far focused on patients' defense use. However, also the defensive functioning of therapists might be significant because of its potential in promoting changes in the patient's overall defensive functioning by sharing their higher-level understanding of a given situation and letting the patient have the opportunity to learn how to cope more successfully. This exploratory case study is the first to examine therapist's defense mechanisms and their relationship to changes in the patient's defensive functioning evaluated at different times throughout psychoanalytic treatment. We assessed the use of defense mechanisms with the Defense Mechanisms Rating Scales in 20 sessions collected at three phases (early, middle and late) of the psychoanalytic treatment. For each session, we identified therapist's and patient's defenses, defense levels and overall defensive functioning, with particular attention to the sequence of consecutively activated defenses within the therapeutic dyad. Results showed that the patient's defensive functioning tended to gradually improve over the course of the treatment, with a slight decrease at the end. Therapists' overall defensive functioning remained stable throughout the treatment with values in the range of high-neurotic and mature defenses. Assessment of the dyadic interaction between therapist and patient's use of defenses showed that within-session, the patient tended to use the same individual defenses that the therapist used, which was especially pronounced in the initial phases of the treatment. Towards the end of the treatment, once there was a stable shared knowledge, the patient started to explore using new, higher-level defenses on her own, independent from what defenses the therapist used. Our findings emphasized the analyst's role in encouraging the development of more effective ways of coping in the patient, confirming previous theoretical and empirical research regarding the improvement of patient's defensive functioning in psychotherapy. The alterations in these coping strategies, also called high-adaptive defenses, as part of the therapist-patient interaction demonstrate the importance of studying defenses as an excellent process-based outcome measure. The measurement of the degree to which the analyst models and illustrates these superior coping methods to the patient is a prime vehicle for supporting internalization of these skills by the patient.

Objectives: Real relationship (RR) refers to a genuine human relationship between client and therapist, that has been found to be positively related to treatment outcome, and to predict unique variance in outcome over and above the working alliance. However, thus far, the measurement of RR has been limited to self-report. We aimed to develop an observer-rated version of the RR measure (RR-O) to assess RR in therapy sessions., Methods: We adapted items from the self-report measures to an observer rated measure, which was reviewed by RR experts. The final 24-item RR-O was rated in 540 session transcripts from 27 psychoanalytic treatments that already had existing process and outcome scores., Results: The RR-O showed good internal consistency and good interrater reliability. In hierarchical EFA, items clustered into a general RR factor, and client realism, client genuineness, therapist genuineness, and therapist realism group factors. In addition, the RR-O was positively related to another RR measure and to the therapeutic alliance., Conclusion: The RR-O shows initial reliability and validity as an observer-rated measure of the RR to be used in post-hoc psychotherapy research. Future research should clarify the relation between RR-O and treatment outcome.

Background: Prolonged fever for more than a week or fever of unknown origin in pediatric patients with or without soft tissue infection should raise suspicion for Bartonella henselae infection. Case Report: A 10-year-old female presented to urgent care with a "bug bite" on the left ring finger, cough, and 2 to 3 days of low-grade fever. Ten days later, her symptoms progressed to soft tissue swelling of the left elbow without fracture on radiograph. Magnetic resonance imaging revealed multiple reniform masses with avid contrast enhancement consistent with suppurative adenitis. She was admitted for irrigation and debridement. The patient underwent surgical debridement with removal of infected lymph nodes. Histology revealed necrotizing granulomatous lymphadenitis. Polymerase chain reaction was positive for B henselae . Antibody titer revealed B henselae immunoglobulin G titer of 1:512 (reference, 1:64), and negative immunoglobulin M titers were indicative of mature immune response. The patient was treated with azithromycin 250 mg tablets twice daily for 3 days followed by 3 days of the 250 mg tablet once daily. Follow-up showed resolution of infection without symptoms concerning for visceral organ infection. Conclusion: While the patient's initial presentation was vague, a complete history, quick follow-up, and decisive intervention prevented significant sequelae such as visceral organ involvement., (©2024 by the author(s); Creative Commons Attribution License (CC BY).)

Background: Distraction therapy use such as virtual reality is novel in the pediatric orthopedic field. In this study, we use subjective and objective metrics to evaluate virtual reality efficacy to reduce anxiety and pain in a pediatric orthopedic cohort., Methods: A prospective randomized controlled trial included patients between age 5 and 17 years, presenting to a tertiary care pediatric orthopedic clinic. Parallel groups underwent orthopedic procedures in clinic, utilizing immersive and interactive virtual reality distraction therapies versus standard of care. Procedures included cast application, cast removal, bone pin removal, and fracture reduction. All preprocedure parameters were similar between the groups. Primary outcome was the difference between maximum procedural heart rate and baseline. Secondary outcomes included Wong Baker FACES Rating Scale (Wong & Baker, 1988, Oklahoma, USA) for pain and Visual Analog Scale scores for anxiety., Results: Ninety-five patients (66 M, 29 F) underwent 59 cast removals, 26 cast applications, 7 percutaneous pin removals, and 3 fracture reductions. Average patient age in the virtual reality and control cohorts was 10.1 (5-17) and 10.6 (5-17), respectively. Average change in maximum heart rate in the virtual reality and control groups was 10.6 ± 10.1 versus 18.4 ± 11.0 (p = 0.00048). The virtual reality group demonstrated trends toward lower perceived anxiety (1.7 ± 2.8 versus 2.9 ± 3.6, p  = 0.0666) when compared to controls., Conclusions: This level 1 study is the first to utilize objective biometric measurements to evaluate use of interactive virtual reality during multiple types of pediatric orthopedic procedures in the clinical setting. The findings suggest that an interactive and immersive virtual reality experience can be effective in reducing pain and anxiety., Level of Evidence: Level 1, Randomized Controlled Trial., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Objective: In an attempt to operationalize an implicit aspect of the therapeutic relationship, this study assesses reciprocal linguistic style entrainment (rLSM) between the patient and therapist. rLSM is defined as the dynamic adjustment of function word usage to synchronize or to be in rhythm with another person as they change over time., Method: In this exploratory study, levels of rLSM per talk turn were analyzed for 540 sessions of 27 long-term psychoanalytic treatments in relation to treatment outcomes., Results: Within sessions, rLSM appeared to decrease by the end of sessions and followed a negative linear trajectory, β linear  = -0.0002, SE  < .001, t  = -13.04, p  < .001. Between sessions, rLSM showed significant variability such that neither a linear, nor a quadratic, nor a cubic trend line fit the session-by-session change over treatment. On average, therapist talk turns had significantly lower rLSM than patient talk turns, while accounting for the nested nature of the data using multilevel models β SpeakerT  = -0.033, SE  = 0.009, t  = -3.65, p  < .001. Levels of rLSM did not relate to treatment outcome., Conclusion: Most of the rLSM variance was at the within-patient and within-session level. rLSM was no indicator of psychoanalytic treatment outcomes.

Variations in the Dlg2 gene have been linked to increased risk for psychiatric disorders, including schizophrenia, autism spectrum disorders, intellectual disability, bipolar disorder, attention deficit hyperactivity disorder, and pubertal disorders. Recent studies have reported disrupted brain circuit function and behaviour in models of Dlg2 knockout and haploinsufficiency. Specifically, deficits in hippocampal synaptic plasticity were found in heterozygous Dlg2+/- rats suggesting impacts on hippocampal dependent learning and cognitive flexibility. Here, we tested these predicted effects with a behavioural characterisation of the heterozygous Dlg2+/- rat model. Dlg2+/- rats exhibited a specific, mild impairment in reversal learning in a substrate deterministic bowl-digging reversal learning task. The performance of Dlg2+/- rats in other bowl digging task, visual discrimination and reversal, novel object preference, novel location preference, spontaneous alternation, modified progressive ratio, and novelty-suppressed feeding test were not impaired. These findings suggest that despite altered brain circuit function, behaviour across different domains is relatively intact in Dlg2+/- rats, with the deficits being specific to only one test of cognitive flexibility. The specific behavioural phenotype seen in this Dlg2+/- model may capture features of the clinical presentation associated with variation in the Dlg2 gene., (© 2023 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.)

China has reconfigured the global value chains of a wide range of commodities. This includes carrageenan, a polysaccharide extracted from specific types of red seaweeds used as a gelling and thickening agent in a wide range of applications. In the past 20 years, China has moved to centre stage in the global carrageenan processing sector, with wide-ranging implications for seaweed producing nations and farmers. This is especially the case for Indonesia, a pivotal carrageenan seaweeds producer that exports almost all seaweed to China, cemented by large Chinese investments in processing in Indonesia. Despite the importance, there is a dearth of studies on the Chinese domestic industry and associated trade and investment flows. This study fills the gap by triangulating a range of detailed industry, statistical and interview data, in multiple language sources. It finds that Chinese trade and investment linkages is of net benefit to Indonesia but that Indonesian government agencies at both central and local levels can begin to introduce terms in their favour., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2023.)

Karst terrain seasonal monsoonal rainfall is often associated with high concentrations of nitrate-N in streams draining agricultural land. Such high concentrations can pose problems for environmental and human health. However, the relationship between rainfall events that mobilize nitrate and resulting nitrate export remains poorly understood in karst terrain. To better understand the processes that drive nitrate dynamics during rainfall events, the characteristics of individual rainfall events were analyzed using sensor technology. Thirty-eight rainfall events were separated from the high-frequency dataset spanning 19 months at a karst spring site. The results revealed that nitrate-discharge (N-Q) hysteresis in 79% of rainfall events showed anticlockwise hysteresis loop patterns, indicating nitrate export from long distances within short event periods. Karstic hydrological connectivity and source availability were considered two major determining factors of N-Q hysteresis. Gradual increase in hydrological connectivity during intensive rainfall period accelerated nitrate transportation by karst aquifer systems. Four principal components (PCs, including antecedent conditions PC1&3 and rainfall characteristics PC2&4 explained 82% of the cumulative variance contribution to the rainfall events. Multiple linear regression of four PCs explained more than 50% of the variation of nitrate loading and amplitude during rainfall events, but poorly described nitrate concentrations and hydro-chemistry parameters, which may be influenced by other factors, e.g., nitrate transformation, fertilization time and water-rock interaction. Although variation of N concentration during event flow is evident, accounting for antecedent conditions and rainfall factors can help to predict rainfall event N loading during rainfall events. Pollution of the karstic catchment occurred by a flush of nitrate input following rainfall events; antecedent and rainfall conditions are therefore important factors to consider for the water quality management. Reducing source availability during the wet season may facilitate to reduction of nitrogen loading in similar karst areas., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This is the second report (part 2) of an investigation whose general objective was to provide evidence regarding the trustworthiness of the Three-Level Model (3-LM). Three groups of analysts from different IPA regions worked with this model on the same clinical case., Specific Objectives: 1) To analyze group output with the same structured qualitative methodology (part 1); 2) To compare the results of the 3-LM group output reported in the 3-LM forms with the process-outcome measures used in the clinical case (part 2); 3) To describe the presence-absence of anchor points in the groups, their similarities and differences (part 2); 4) To exemplify the interrelationship of the three levels of the 3-LM in relation to patient change and the analyst's interventions (part 2)., Sample: verbatim transcript of three 3-LM groups., Materials: 3-LM forms, process and outcome measures (APS, DIS and PHI-RADIO) and Operationalized Psychodynamic Diagnosis., Results: Objective 2 found global convergence in the PHI, DIS and APS scores across sessions. Objective 3 showed convergences and divergences in the themes relating to the anchor points. Objective 4 showed how an anchor point corresponds to the focus of treatment and how this is present in the analyst's attitudes and interventions., Discussion: The results offer preliminary support for the trustworthiness of the 3-LM.

Greenhouse gas emissions from urban rivers play a crucial role in global carbon (C) cycling, this is tightly linked to dissolved C in rivers but research gaps remain. The effects of urbanization and anthropogenic land-use change on riverine dissolved carbon dynamics were investigated in a temperate river, the River Kelvin in UK. The river was constantly a source of methane (CH 4 ) and carbon dioxide (CO 2 ) to the atmosphere (excess concentration of CH 4 ranged from 13 to 4441 nM, and excess concentration of CO 2 ranged from 2.6 to 230.6 μM), and dissolved C concentrations show significant spatiotemporal variations (p < 0.05), reflecting a variety of proximal sources and controls. For example, the concentration variation of dissolved CH 4 and dissolved CO 2 were heavily controlled by the proximity of coal mine infrastructure in the tributary near the river head (~ 2 km) but were more likely controlled by adjacent landfills in the midstream section of the rivers main channel. Concentration and isotopic evidence revealed an important anthropogenic control on the riverine export of CO 2 and dissolved organic carbon (DOC). However, dissolved inorganic carbon (DIC) input via groundwater at the catchment scale primarily controlled the dynamics of riverine DIC. Furthermore, the positive relationship between the isotopic composition of DIC and CO 2 (r = 0.79, p < 0.01) indicates the DIC pool was at times also significantly influenced by soil respiratory CO 2 . Both DIC and DOC showed a weak but significant correlation with the proportion of urban/suburban land use, suggesting increased dissolved C export resulting from urbanization. This research elucidates a series of potentially key effects anthropogenic activities and land-use practices can have on riverine C dynamics and highlights the need for future consideration of the direct effects urbanization has on riverine C dynamics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Glaucoma is a leading cause of blindness. Current glaucoma medications work by lowering intraocular pressure (IOP), a risk factor for glaucoma, but most treatments do not directly target the pathological changes leading to increased IOP, which can manifest as medication resistance as disease progresses. To identify physiological modulators of IOP, we performed genome- and exome-wide association analysis in >129,000 individuals with IOP measurements and extended these findings to an analysis of glaucoma risk. We report the identification and functional characterization of rare coding variants (including loss-of-function variants) in ANGPTL7 associated with reduction in IOP and glaucoma protection. We validated the human genetics findings in mice by establishing that Angptl7 knockout mice have lower (~2 mmHg) basal IOP compared to wild-type, with a trend towards lower IOP also in heterozygotes. Conversely, increasing murine Angptl7 levels via injection into mouse eyes increases the IOP. We also show that acute Angptl7 silencing in adult mice lowers the IOP (~2-4 mmHg), reproducing the observations in knockout mice. Collectively, our data suggest that ANGPTL7 is important for IOP homeostasis and is amenable to therapeutic modulation to help maintain a healthy IOP that can prevent onset or slow the progression of glaucoma., (© 2022. The Author(s).)

China is the largest global consumer of infant milk formula (IMF). Chinese consumer preferences towards IMF have evolved over time but have also been rocked in recent years by COVID-19 with major implications for the IMF industry, globally and within China. This study is the first to document parents' preferences toward IMF since the outbreak. We used novel methods to do so, through an online choice experiment of 804 participants that included risk perceptions and socio-demographic variables. Our study finds that Chinese parents continue to prioritize quality and safety attributes of IMF represented by functional ingredients, organic labelling and traceability information. Notably, it also finds greatly increased confidence in Chinese domestically produced IMF and an underlying preference away from expensive products. This implies that the era of 'go for foreign' and 'go for the most expensive' in IMF purchasing may be coming to an end. The shift in sentiment is driven by the longer-term revitalization of the Chinese dairy industry, accelerated by COVID-19. Understanding these trends will be of major benefit to both Chinese producers and non-Chinese exporters of IMF.

Objective: The following report describes the evaluation of the ISPAD Science School for Physicians (ISSP) and for Healthcare Professionals (ISSHP) in terms of their efficiency and success., Methods: All past attendees from 2000-2019 ISSP and 2004-2019 ISSHP programs were invited to respond to an online survey to assess perceived outcomes of the programs on career development, scientific enhancement, scientific networking, and social opportunities., Results: One-third of the past ISSP (129/428), and approximately 43% of the past ISSHP attendees (105/245) responded to the surveys. Most of ISSP attendees reported that the programs supported their career (82%) by helping to achieve a research position (59%), being engaged with diabetes care (68%) or research (63%) or starting a research fellowship (59%). Responders indicated that ISSP was effective in increasing interest in diabetes research (87%) and enhancing the number (66%) and quality (83%) of scientific productions, and promotion of international collaborations (86%). After the ISSP, 34% of responders received research grants. From the first round of the ISSHP survey (2004-2013), responders reported have improved knowledge (60%), gained more confidence in research (69%), undertaken a research project (63%), and achieved a higher academic degree (27%). From the second round (2014-2019), participants indicated that the program was valuable/useful in workplace (94%) through understanding (89%) and conducting (68%) research and establishing communication from other participants (64%) or from faculty (42%). After the ISSHP, 17% had received awards., Conclusions: From the participants' viewpoint, both programs were effective in improving engagement with diabetes research, supporting career opportunities, increasing scientific skills, and enhancing networking and research activities., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Copy number variants indicating loss of function in the DLG2 gene have been associated with markedly increased risk for schizophrenia, autism spectrum disorder, and intellectual disability. DLG2 encodes the postsynaptic scaffolding protein DLG2 (PSD93) that interacts with NMDA receptors, potassium channels, and cytoskeletal regulators but the net impact of these interactions on synaptic plasticity, likely underpinning cognitive impairments associated with these conditions, remains unclear. Here, hippocampal CA1 neuronal excitability and synaptic function were investigated in a novel clinically relevant heterozygous Dlg2+/- rat model using ex vivo patch-clamp electrophysiology, pharmacology, and computational modelling. Dlg2+/- rats had reduced supra-linear dendritic integration of synaptic inputs resulting in impaired associative long-term potentiation. This impairment was not caused by a change in synaptic input since NMDA receptor-mediated synaptic currents were, conversely, increased and AMPA receptor-mediated currents were unaffected. Instead, the impairment in associative long-term potentiation resulted from an increase in potassium channel function leading to a decrease in input resistance, which reduced supra-linear dendritic integration. Enhancement of dendritic excitability by blockade of potassium channels or activation of muscarinic M1 receptors with selective allosteric agonist 77-LH-28-1 reduced the threshold for dendritic integration and 77-LH-28-1 rescued the associative long-term potentiation impairment in the Dlg2+/- rats. These findings demonstrate a biological phenotype that can be reversed by compound classes used clinically, such as muscarinic M1 receptor agonists, and is therefore a potential target for therapeutic intervention., (© 2022. The Author(s).)

Conjugation of oligonucleotide therapeutics, including small interfering RNAs (siRNAs) or antisense oligonucleotides, to N -acetylgalactosamine (GalNAc) ligands has become the primary strategy for hepatocyte-targeted delivery, and with the recent approvals of GIVLAARI (givosiran) for the treatment of acute hepatic porphyria, OXLUMO (lumasiran) for the treatment of primary hyperoxaluria, and Leqvio (inclisiran) for the treatment of hypercholesterolemia, the technology has been well validated clinically. Although much knowledge has been gained over decades of development, there is a paucity of published literature on the drug metabolism and pharmacokinetic properties of GalNAc-siRNA. With this in mind, the goals of this minireview are to provide an aggregate analysis of these nonclinical absorption, distribution, metabolism, and excretion (ADME) data to build confidence on the translation of these properties to human. Upon subcutaneous administration, GalNAc-conjugated siRNAs are quickly distributed to the liver, resulting in plasma pharmacokinetic (PK) properties that reflect rapid elimination through asialoglycoprotein receptor-mediated uptake from circulation into hepatocytes. These studies confirm that liver PK, including half-life and, most importantly, siRNA levels in RNA-induced silencing complex in hepatocytes, are better predictors of pharmacodynamics (PD) than plasma PK. Several in vitro and in vivo nonclinical studies were conducted to characterize the ADME properties of GalNAc-conjugated siRNAs. These studies demonstrate that the PK/PD and ADME properties of GalNAc-conjugated siRNAs are highly conserved across species, are largely predictable, and can be accurately scaled to human, allowing us to identify efficacious and safe clinical dosing regimens in the absence of human liver PK profiles. SIGNIFICANCE STATEMENT: Several nonclinical ADME studies have been conducted in order to provide a comprehensive overview of the disposition and elimination of GalNAc-conjugated siRNAs and the pharmacokinetic/pharmacodynamic translation between species. These studies demonstrate that the ADME properties of GalNAc-conjugated siRNAs are well correlated and predictable across species, building confidence in the ability to extrapolate to human., (Copyright © 2022 by The Author(s).)

Introduction: Induction of labor (IOL) is rising globally and is growing steadily in the state of New South Wales, Australia. There are numerous methods of induction of labor, including the double balloon catheter (DBC). There is minimal evidence on women's attitudes and experiences and clinician's opinions on the use of the DBC. This study aims to explore the views regarding DBC insertion and effectiveness from women induced with a DBC and clinicians involved in the catheter insertion and care., Methods: This study is a descriptive survey of two prospective, de-identified, self-reported questionnaires which were completed in 2016. One questionnaire was administered to term pregnant women that were admitted to the antenatal ward post IOL, and the other was completed by midwives and obstetric doctors working in the ward at the time., Results: The DBC appeared to be a well-accepted method of cervical ripening among women (61%) and clinicians (>82%). Success of DBC to achieve an artificial rupture of membrane post removal, directly correlates to women's acceptance (61%). While most clinicians (59-67%) perceived insertion of DBC in an outpatient setting and then women discharged home was appropriate, only 13% of women were in favor. On the logistics of the procedure in respect to insertion and removal of the DBC, there were differences of opinion, with only 43% of women, 77% of midwives and 33% of doctors stating that the timing of insertion and removal needed to be improved., Conclusions: This study highlights the need to undertake qualitative research to further explore women's views and perceptions on IOL in order to ensure that clinical practice is woman-centered and evidenced-based, and to guide policy and protocol., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2022 Waldron S. et al.)

Genetic studies implicate disruption to the DLG2 gene in copy number variants as increasing risk for schizophrenia, autism spectrum disorders and intellectual disability. To investigate psychiatric endophenotypes associated with DLG2 haploinsufficiency (and concomitant PSD-93 protein reduction) a novel clinically relevant Dlg2 +/- rat was assessed for abnormalities in anxiety, sensorimotor gating, hedonic reactions, social behaviour, and locomotor response to the N-Methyl-D-aspartic acid receptor antagonist phencyclidine. Dlg gene and protein expression were also investigated to assess model validity. Reductions in PSD-93 messenger RNA and protein were observed in the absence of compensation by other related genes or proteins. Behaviourally Dlg2 +/- rats show a potentiated locomotor response to phencyclidine, as is typical of psychotic disorder models, in the absence of deficits in the other behavioural phenotypes assessed here. This shows that the behavioural effects of Dlg2 haploinsufficiency may specifically relate to psychosis vulnerability but are subtle, and partially dissimilar to behavioural deficits previously reported in Dlg2 +/- mouse models demonstrating issues surrounding the comparison of models with different aetiology and species. Intact performance on many of the behavioural domains assessed here, such as anxiety and reward processing, will remove these as confounds when continuing investigation into this model using more complex cognitive tasks., (© 2022 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.)

Background: Despite the fact that literacy instruction is a main focus of primary education, many children struggle to meet nationally set standards., Aims: We aimed to test which components of a comprehensive reading programme (ABRACADABRA: https://eur03.safelinks.protection., Outlook: com/?url=https%3A%2F%2Fdoi.org%2F10.1186%2FISRCTN18254678&data=04%7C01%7Cjanet.vousden%40ntu.ac.uk%7C880280e0b00749df855308d94068a0bb%7C8acbc2c5c8ed42c78169ba438a0dbe2f%7C1%7C0%7C637611640381216902%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C1000&sdata=%2B4U9sGfofkyCPEY7lWz8n3TPoMOAeJMXyFwdhW6EpUw%3D&reserved=0) mediated the effect of the programme on nationally assessed literacy outcomes., Sample: Following blind allocation, 516 Year 1 pupils from 40 schools were randomized to the programme group, and 908 Year 1 pupils, to a control condition., Methods: Pupils in the programme completed 20 weeks of instruction in grapheme/phoneme knowledge, decoding, and comprehension. Control children received regular classroom instruction., Results: Children in the programme group were significantly better at these taught skills after the programme finished (effect sizes: grapheme/phoneme knowledge, β = .33, 95% CI [0.09-0.57]; decoding, β = .26, 95% CI [0.09-0.43]; and comprehension, β = .26, 95% CI [0.05-0.47]). Improvements in the programme group's decoding and comprehension skills fully mediated the improvements in national literacy assessments serving as a delayed post-test 12 months after the programme. Programme group pupils were 2.3 (95% CI [1.4-4.1]) times more likely to achieve/exceed the expected standard in reading, and 1.8 (95% CI [1.2-2.6]) times more likely to achieve/exceed the expected standard in writing due to an increase in the trained skills., Conclusions: These results provide strong evidence that a programme that incorporates decoding and comprehension instruction for typically developing beginning readers improves distal educational outcomes in reading and writing through increasing proficiencies targeted by the reading programme., (© 2021 The Authors. British Journal of Educational Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Contamination of surface and groundwater systems with human and animal faecal matter leads to exposure of reliant populations to disease causing micro-organisms. This exposure route remains a major cause of infection and mortality in developing countries, particularly rural regions. To meet the UN's sustainable development goal 6: Ensure availability and sustainable management of water and sanitation for all, we need to identify the key controls on faecal contamination across relevant settings. We conducted a high-resolution spatial study of E. coli concentration in catchment drainage waters over 6 months in a mixed land-use catchment in the extensive karst region extending across impoverished southwest China. Using a mixed effects modelling framework, we tested how land-use, karst hydrology, antecedent meteorological conditions, agricultural cycles, hydrochemistry, and position in the catchment system affected E. coli concentrations. Land-use was the best predictor of faecal contamination levels. Sites in urban areas were chronically highly contaminated, but water draining from agricultural land was also consistently contaminated and there was a catchment wide pulse of higher E. coli concentrations, turbidity, and discharge during paddy field drainage. E. coli concentration increased with increasing antecedent rainfall across all land-use types and compartments of the karst hydrological system (underground and surface waters), but decreased with increasing pH. This is interpreted to be a result of processes affecting pH, such as water residence time, rather than the direct effect of pH on E. coli survival. Improved containment and treatment of human waste in areas of higher population density would likely reduce contamination hotspots, and further research is needed to identify the nature and distribution of sources in agricultural land., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Understanding where nitrate is mobilized from and under what conditions is required to reduce nitrate loss and protect water quality. Low frequency sampling may inadequately capture hydrological and biogeochemical processes that will influence nitrate behavior. We used high-frequency isotope sampling and in-situ nitrate sensing to explore nitrate export and transformation in a karst critical zone. Nitrate was mobilised during light rainfall, and transferred from soil layers to the karst matrix, where some nitrate was retained and denitrified. Nitrate isotopic composition changed rapidly during the rising limb of events and slowly during the falling limb. The main nitrate source was synthetic fertiliser (up to 80% during event flow), transported by conduit flow following high rainfall events, and this contribution increased significantly as discharge increased. Soil organic nitrogen contribution remained constant indicating at baseflow this is the primary source. Isotope source appointment of nitrate export revealed that synthetic fertilizer accounted for more than half of the total nitrate export, which is double that of the secondary source (soil organic nitrogen), providing valuable information to inform catchment management to reduce nitrate losses and fluvial loading. Careful land management and fertilizer use are necessary to avoid nitrate pollution in the karst agroecosystem, for example by timing fertilizer applications to allow for plant uptake of nitrate before rainfall can flush it from the soils into the karst and ultimately into catchment drainage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Transport of nitrogen (N) in karst areas is more complex than in non-karst areas due to marked heterogeneity of hydrodynamic behaviour in the karst critical zone. Here, we present a novel, distributed, coupled hydrological-biogeochemical model that can simulate water and nitrogen transport in the critical zone of karst catchments. This new model was calibrated using integrated hydrometric, water stable isotope, and nitrogen-N concentration data at the outflow of Houzhai catchment in Guizhou province of Southwest China. Hydrological dynamics appears to control N load from the study catchment. Combining flow discharge and water stable isotopes significantly constrained model parameterisation and mitigate the equifinality effects of parameters on the simulated results. Karst geomorphology and land use have functional effects on spatiotemporal variations of hydrological processes and nitrogen transport. In the study catchment, agricultural fertilizer was the largest input source of N, accounting for 86% of the total. Plant uptake consumed about 45% of inputs, primarily in the low-lying valley bottom areas and the plain covered by relatively thick soils. Thus, a large amount of N released from soil reservoirs to the epikarst (via fractures or sinkholes) is then exported to the underground channel in the limestone area to the south. This N draining into groundwater could lead to extensive, potentially long-term contamination of the karst system. Therefore, improving the efficiency of fertilization and agricultural management in valleys/depressions is an urgent need to reduce N losses and contamination risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Hydrochemical behavior and dissolved carbon dynamics are highly-sensitive to hydrological variations in the monsoon-influenced karstic critical zone which has high chemical weathering rates and experiences strong anthropogenic impact. Continuous high-frequency monitoring in the spring outlet of a karstic catchment in Southwestern China revealed that most hydrochemical variables changed distinctively in response to hydrologic variations, influenced by mixing of different sources and miscellaneous biogeochemical processes. Na + , K + and SO 4 2 - varied significantly with hydrology, showing weak chemostatic behavior controlled by dilution. The flushing effect and random behavior of NO 3 - and Cl - likely reflect agricultural inputs from high throughflow. Soil CO 2 in infiltrated water supports carbonate weathering, enabling DIC (dissolved inorganic carbon) and weathering products (e.g., Ca 2+ and Mg 2+ ) to maintain chemostatic behavior. Biogenic DIC exhibited a stronger chemostatic response than carbonate sources and was the foremost control in DIC behavior. Carbon exchange between DIC and DOC (dissolved organic carbon) did not significantly influence DIC concentration and δ 13 C due to very low DOC concentration. More DOC was exported by flushing from increasing discharge. Hysteretic analysis indicated that the transport processes were controlled by proximal sources mixing and diverse mobilization in various periods responding to rainstorms. NO 3 - and Cl - presented different hysteresis behavior as sourced from agricultural activities. DOC increased on the hydrograph rising limb and was controlled by a transport-limited regime. However, the hysteresis behavior of most weathering products and DIC were regulated by a process-limited regime in the karstic critical zone. Overall, biogeochemical processes, hydrogeological properties, storm intensity/magnitude and the timing of storms (antecedent conditions) are main factors influencing the response of hydrochemical variables and dissolved carbon to storm events., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

The sensitivity for singlet oxygen ( 1 O 2 ) of two convenient 1 O 2 probes, 1,3-diphenylisobenzofuran (DPBF) and 9,10-Anthracenediyl-bis(methylene)dimalonic acid (ABDA), has been investigated in different aqueous environments. Both probes are commercially available at reasonable cost and can be used with standard UV-vis spectrometers. Although DPBF is not soluble in neat water and is not specific to the detection of 1 O 2 , it has very high, essentially diffusion-limited, reactivity towards 1 O 2 ; it can trap up to 50% of all 1 O 2 created in alcohol/water or micellar solution, and even more when replacing H 2 O by D 2 O, which makes it highly useful when the process under investigation does not yield much 1 O 2 . On the other hand, ABDA has a much lower reactivity, reacting with only 2% of the singlet oxygen generated in H 2 O, as well as a smaller extinction coefficient, resulting in a much smaller spectroscopic response, but is soluble in neat water and is specific for 1 O 2 , allowing for discrimination from other reactive oxygen species. The results presented here not only allow a comparative assessment of the usefulness of the two 1 O 2 probes, but also provide a reference for an accurate absolute quantification of the amount of 1 O 2 generated in an experiment from the observed absorbance bleach., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Wind farms can help to mitigate increasing atmospheric carbon (C) emissions. However, disturbance caused by wind farm development must not have lasting deleterious impacts on landscape C sequestration. To understand the effects of wind farm development on peatlands, we monitored streamwater at Europe's second largest onshore wind farm (539 MW), Whitelee, Scotland, for 31 months. Using nested catchment sampling to understand impacts on water quality, increasing macronutrient concentrations and exports were associated with wind farm development, particularly forest-felling and borrow pits. Low/poor water quality occurred in small headwater catchments most disturbed by development. At the site exit, dissolved organic C and soluble reactive phosphorus (SRP) concentrations increased during construction, though [SRP] recovery occurred within 2 years. Since C was lost and streamwater quality negatively affected, we propose future good practice measures for wind farm development, including limiting total disturbance within individual catchments and locating borrow pits, where deemed necessary, off site avoiding peatlands.

Microplastics (MPs, <5 mm in size) are classified as emerging contaminants but treatment processes are not designed to remove these small particles. Wastewater treatment systems have been proposed as pathways for MPs pollution to receiving waters but quantitative and qualitative data on MP occurrence and transport remains limited, hindering risk assessment and regulation. Here, for the first time, the stepwise abundance and loading of MPs (60-2800 μm) in a tertiary wastewater treatment plant in the UK was assessed by sampling from May 2017 to February 2018. Microplastics were found in all sampling campaigns, with an average inflow of 8.1 × 10 8 (95% CI, 3.8 × 10 8 to 1.2 × 10 9 ) items day -1 . Their prevalence decreased from influent to final effluent. Overall abundances decreased on average by 6%, 68%, 92%, and 96% after the pre-treatment, primary, secondary, and tertiary treatment stages respectively, although considerable variability occurred throughout the year. Sufficient particles remained in the treated effluent to generate an average discharge of 2.2 × 10 7 (95% CI, 1.2 × 10 7 to 3.2 × 10 7 ]) particles day -1 to the recipient river. Secondary MPs were predominant, while primary MP abundances were minimal. Fibres comprised 67% of all items, followed by films (18%) and fragments (15%). Chemical characterisation confirmed the presence of different types of polymers, with polypropylene fibres and fragments most abundant (23%). This research informs understanding of how wastewater effluent may channel MPs to the natural environment and their composition, and helps understand control points for optimising advanced treatment processes., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Karst aquifers have distinctive hydrology and supply 25% of the world's population with drinking water, making them a critical geological setting for understanding and managing microbial water pollution. Rainfall causes elevated concentrations and loading of faecal microorganisms, e.g. E. coli , in catchment surface and groundwater systems, increasing the risk of human exposure to faecally-contaminated water. However, effective management of microbial water quality in complex karst catchments is constrained by limited understanding of E. coli - discharge responses to rainfall. We analysed how rainfall events of varying magnitude (2.4-100 mm) control E. coli- discharge dynamics at increasing spatial scales in a mixed land-use karst catchment in southwest China. During the wet season, hourly water sampling was undertaken throughout five storm events to characterise in high detail E. coli emergence with resulting flow across multiple sites of varying catchment area, stream order, and land-use. E. coli concentration was found to increase by 1-3 orders of magnitude following rainfall events. Maximum E. coli concentration and speed of E. coli recession were influenced by rainfall (amount, intensity), timing of agricultural activities, and position in the hydrological system. For high intensity events ∼90% of the cumulative E. coli export occurred within 48 h. E. coli concentration increased with increasing discharge at all sites. E. coli concentration at low discharge was higher in the headwaters than at the catchment outlet, while the rate of increase in E. coli concentration with increasing discharge appears to follow the opposite trend, being higher at the catchment outlet than the headwaters. This was attributed to the decreasing flow path gradient and increasing degree of development of the fissure network, but further event monitoring at varying catchment scales is required to confirm this relationship. The results provide novel insight into how rainfall characteristics combine with land-use and catchment hydrology to control E. coli export in karst landscapes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2019 The Authors.)

Southeast-Asian peat swamp forests have been significantly logged and converted to plantation. Recently, to mitigate land degradation and C losses, some areas have been left to regenerate. Understanding how such complex land use change affects greenhouse gas emissions is essential for modelling climate feedbacks and supporting land management decisions. We carried out field research in a Malaysian swamp forest and an oil palm plantation to understand how clear-felling, drainage, and illegal and authorized conversion to oil palm impacted the C cycle, and how the C cycle may change if such logging and conversion stopped. We found that both the swamp forest and the plantation emit centuries-old CO 2 from their drainage systems in the managed areas, releasing sequestered C to the atmosphere. Oil palm plantations are an iconic symbol of tropical peatland degradation, but CO 2 efflux from the recently-burnt, cleared swamp forest was as old as from the oil palm plantation. However, in the swamp forest site, where logging had ceased approximately 30 years ago, the age of the CO 2 efflux was modern, indicating recovery of the system can occur. 14 C dating of the C pool acted as a tracer of recovery as well as degradation and offers a new tool to assess efficacy of restoration management. Methane was present in many sites, and in higher concentrations in slow-flowing anoxic systems as degassing mechanisms are not strong. Methane loading in freshwaters is rarely considered, but this may be an important C pool in restored drainage channels and should be considered in C budgets and losses.

Background: Patella instability and medial patellofemoral ligament (MPFL) injury are frequently encountered in pediatric patients. MPFL reconstruction is often chosen to treat this condition with good results; however, no consensus has been reached about which graft or technique to use. The purpose of this study was to evaluate the differences in graft survivorship, clinical outcomes (assessed with Kujala scores), and cost between autograft and allograft usage in MPFL reconstruction in pediatric patients. Methods: In this retrospective review of patients who underwent MPFL reconstruction between 2012-2015, autograft gracilis tendon was used for Group 1, and allograft gracilis tendon was used for Group 2. Outcomes were graft survivorship, postoperative Kujala scores, operative time, costs, graft size, and tibial tubercle-trochlear groove distance. Results: Fifty-six patients were included in this study, 21 in Group 1 and 35 in Group 2. No differences in age, sex, or chronicity were seen between the groups. Patients in Group 1 had longer operative times (134.5 minutes vs 97.3 minutes, P= 0.0002), higher rates of graft failure (28.6% vs 0%, P =0.0037), and lower Kujala scores (80.3 vs 92.1, P =0.0032) compared to Group 2. All graft failures occurred in patients with chronic patella dislocations and occurred an average of 13.8 months postoperatively. Overall, autograft was costlier than allograft because of the cost of reoperation. Conclusion: This study supports the use of allograft for chronic patellar instability because of improved graft survivorship and clinical outcome scores, as well as the lower cost and reoperation rate.

Understanding of the sources, fate, and impact of microplastics (MPs, < 5 mm) remains limited, particularly in freshwater environments, while limited comparability across available surveys hinders adequate monitoring and risk assessment of these contaminants. Here, the distribution of microscopic debris in an urban river close to the marine environment in the West of Scotland was investigated to assess concentration and distribution of primary and secondary MPs. Also, the efficiency of light and scanning electron microscopy with energy-dispersive spectroscopy (SEM-EDS) was evaluated for characterisation and quantification of MPs sized 2.8 mm-11 μm. Bank sediment samples were collected twice from the River Kelvin in Glasgow and were size-fractionated and processed for extraction of MPs by density separation. Sample MPs spiking and use of procedural blanks allowed the influence of processing on field data quality to be considered. Total abundances were 161-432 MPs kg -1 dry sediment, with fibres as the dominant type, comprising > 88% of total counts. Nevertheless, fibres in blanks suggest potential contributions from atmospheric contamination. Moreover, fibres concentrated mainly in fractions < 0.09 mm suggesting that their fate may be influenced by drivers of fine sediment dynamics in rivers. While no primary MPs were observed, metallic and glass pellets were present in high abundances in settled material and could be easily misidentified by visual inspection, demonstrating that compositional analysis is needed to avoid analytical errors from MP misidentification and overestimation. SEM-EDS allowed for a quick screening of plastic vs non-plastic pellets and improved identification of smaller fragments, whereas more advanced techniques are needed for proper identification of fibres. This study is the first to report on MPs in freshwater rivers in Scotland and suggests that diffuse sources of pollution may be delivering secondary MPs to the river. Their sources, fate, and risk in these systems will thus warrant further attention.

Large amounts of carbon are stored in northern peatlands. There is concern that greater wildfire severity following projected increases in summer drought will lead to higher post-fire carbon losses. We measured soil carbon dynamics in a Calluna heathland and a raised peat bog after experimentally manipulating fire severity. A gradient of fire severity was achieved by simulating drought in 2 × 2 m plots. Ecosystem respiration (ER), net ecosystem exchange (NEE), methane (CH 4 ) flux and concentration of dissolved organic carbon ([DOC], measured at the raised bog only) were measured for up to two years after burning. The response of these carbon fluxes to increased fire severity in drought plots was similar to plots burnt under ambient conditions associated with traditional managed burning. Averaged across all burnt plots, burning altered mean NEE from a net carbon sink at the heathland (-0.33 μmol CO 2 m -2 s -1 in unburnt plots) to a carbon source (0.50 μmol m -2 s -1 in burnt plots) and at the raised bog (-0.38 and 0.16 μmol m -2 s -1 , respectively). Burning also increased CH 4 flux at the raised bog (from 1.16 to 25.3 nmol m -2 s -1 in the summer, when it accounted for 79% of the CO 2 -equivalent emission). Burning had no significant effect on soil water [DOC]., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Calluna vulgaris-dominated habitats are valued for ecosystem services such as carbon storage and for their conservation importance. Climate and environmental change are altering their fire regimes. In particular, more frequent summer droughts will result in higher severity wildfires. This could alter the plant community composition of Calluna habitats and thereby influence ecosystem function. To study the effect of fire severity on community composition we used rain-out shelters to simulate drought prior to experimental burns at two Calluna-dominated sites, a raised bog and a heathland. We analysed species abundance in plots surveyed ca. 16 months after fire in relation to burn severity (indicated by fire-induced soil heating). We found that fire severity was an important control on community composition at both sites. Higher fire severity increased the abundance of ericoids, graminoids and acrocarpous mosses, and decreased the abundance of pleurocarpous mosses compared to lower severity fires. At the raised bog, the keystone species Sphagnum capillifolium and Eriophorum vaginatum showed no difference in regeneration with fire severity. Species and plant functional type beta-diversity increased following fire, and was similar in higher compared to lower severity burns. Our results further our understanding of the response of Calluna-dominated habitats to projected changes in fire regimes, and can assist land managers using prescribed fires in selecting burning conditions to achieve management objectives., (Copyright © 2018 Elsevier Ltd. All rights reserved.)