Bryozoan beds in northern Italy as a shallow-water expression of environmental changes during the Oligocene isotope event 1

Shifts in carbonate-producing biotic communities in the geological record provide evidence of past environmental changes in the neritic realm. The shallow-marine Calcare di Nago Formation exposed in the San Valentino section (northern Italy) covers the Late Eocene and Earliest Oligocene. The succession is characterized by the occurrence of light-dependent biota such as coralline algae and larger benthic foraminifera. In the uppermost part of the section, however,\ the fossil association is dominated by bryozoans, which are filter-feeder organisms. This ca. 12 m thick interval locally contains up to 86% bryozoans, while coralline algae as well as larger benthic foraminifera are absent. Coralline algae and nummulitid foraminifera recover in the upper part of the bryozoan beds, whereas orthophragminids do not recover. The gradual disappearance of larger foraminifera and coralline algae within the bryozoan-dominated deposits is coeval with a pronounced positive shift in δ¹³C. Based on its biostratigraphic position, this positive shift is interpreted to be linked to the positive shift in δ¹³C recognized in deep-sea records shortly above the Eocene–Oligocene boundary, which in turn is associated to the positive shift in δ¹⁸O leading to the Oi-1 (Oligocene isotope event 1) cooling phase. Total phosphorus content increases in the bryozoan beds, suggesting enhanced nutrient supply to the neritic ecosystem. This phosphorous peak is coeval with the globally recognized increment in ocean productivity around the Oi-1 and δ¹³C positive shift. Thus, disappearance of light-dependent biota and the dominance of bryozoans in the platform carbonates studied are interpreted to result not necessarily from a deepening of the depositional environment but from the combination of lower sea-surface temperatures and the deterioration of underwater light conditions on account of elevated turbidity in surface waters, resulting from enhanced primary productivity. As bryozoan beds occur in several Italian localities around the Eocene–Oligocene boundary, they are interpreted to represent the regional expression of neritic carbonate depositional systems to global environmental changes occurring at the dawn of an ice-house Earth

Insulin-Like Growth Factor (IGF)-I and -11 and IGFBinding Proteins-l, -2, and -3 in Children and Adolescents with Diabetes Mellitus: Correlation with Metabolic Control and Height Attainment.

The putative effects of diabetes and metabolic control on circulating levels of insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) remain controversial. In the present study, serum levels of IGF-I and IGF-II and IGFBP-1, -2, and -3 were measured in 58 patients (age, 0.8-17 yr) with treated (51 subjects) or untreated (7 subjects) insulin-dependent diabetes mellitus (IDDM) and were compared with the levels in normal subjects. In the untreated patients IGF-I and IGF-II were decreased as compared with the healthy controls. In the treated diabetics IGF-I and IGF-II were reduced; IGFBP-2 (only in prepubertal subjects) and IGFBP-3 were increased. Furthermore, age-adjusted values of IGF-I, IGF-II, and IGFBP-3 were lower in prepubertal than in pubertal patients. Regression analysis revealed a negative correlation between hemoglobin (Hb)A1c and standard deviation scores (SDS) of IGF-I and a positive association between HbA1c and IGFBP-1 SDS or IGFBP-2 SDS. In the treated patients HbA1c was positively related to IGFBP-1 SDS and IGFBP-2 SDS when applying simple regression analysis and to IGFBP-2 SDS when using a multiple regression model. Strong correlations were observed between height SDS and IGF-I SDS, IGF-II SDS, and IGFBP-3 SDS in prepubertal subjects who had had IDDM for at least 2 yr, but not in adolescents. Such correlations have also been found in healthy children and adolescents. In conclusion; 1) IDDM is associated with alterations of the IGF-IGFBP system, which are partially accounted for by differences in metabolic control and pubertal status; 2) the lower plasma concentrations of serum IGF-I may play a role in the pathogenesis of growth impairment of poorly controlled prepubertal, but not pubertal, children and adolescents with IDDM; and 3) in addition, a potential role of the altered IGF-IGFBP system for the development of diabetic late complications is hypothesized

Bryozoan beds in northern Italy as a shallow-water expression of environmental changes during Oligocene isotope event 1

Shifts in carbonate-producing biotic communities in the geological record provide evidence of past environmental changes in the neritic realm. The shallow-marine Calcare di Nago Formation exposed in the San Valentino section (northern Italy) covers the Late Eocene and Earliest Oligocene. The succession is characterized by the occurrence of light-dependent biota such as coralline algae and larger benthic foraminifera. In the uppermost part of the section, however,\ the fossil association is dominated by bryozoans, which are filter-feeder organisms. This ca. 12 m thick interval locally contains up to 86% bryozoans, while coralline algae as well as larger benthic foraminifera are absent. Coralline algae and nummulitid foraminifera recover in the upper part of the bryozoan beds, whereas orthophragminids do not recover. The gradual disappearance of larger foraminifera and coralline algae within the bryozoan-dominated deposits is coeval with a pronounced positive shift in δ13C. Based on its biostratigraphic position, this positive shift is interpreted to be linked to the positive shift in δ13C recognized in deep-sea records shortly above the Eocene-Oligocene boundary, which in turn is associated to the positive shift in δ18O leading to the Oi-1 (Oligocene isotope event 1) cooling phase. Total phosphorus content increases in the bryozoan beds, suggesting enhanced nutrient supply to the neritic ecosystem. This phosphorous peak is coeval with the globally recognized increment in ocean productivity around the Oi-1 and δ13C positive shift. Thus, disappearance of light-dependent biota and the dominance of bryozoans in the platform carbonates studied are interpreted to result not necessarily from a deepening of the depositional environment but from the combination of lower sea-surface temperatures and the deterioration of underwater light conditions on account of elevated turbidity in surface waters, resulting from enhanced primary productivity. As bryozoan beds occur in several Italian localities around the Eocene-Oligocene boundary, they are interpreted to represent the regional expression of neritic carbonate depositional systems to global environmental changes occurring at the dawn of an ice-house Earth

Managed Evolution of Automotive Software Product Line Architectures: A Systematic Literature Study

The rapidly growing number of software-based features in the automotive domain as well as the special requirements in this domain ask for dedicated engineering approaches, models, and processes. Nowadays, software development in the automotive sector is generally developed as product line development, in which major parts of the software are kept adaptable in order to enable reusability of the software in different vehicle variants. In addition, reuse also plays an important role in the development of new vehicle generations in order to reduce development costs. Today, a high number of methods and techniques exist to support the product line driven development of software in the automotive sector. However, these approaches generally consider only partial aspects of development. In this paper, we present an in-depth literature study based on a conceptual model of artifacts and activities for the managed evolution of automotive software product line architectures. We are interested in the coverage of the particular aspects of the conceptual model and, thus, the fields covered in current research and research gaps, respectively. Furthermore, we aim to identify the methods and techniques used to implement automotive software product lines in general, and their usage scope in particular. As a result, this in-depth review reveals that none of the studies represent a holistic approach for the managed evolution of automotive software product lines. In addition, approaches from agile software development are of growing interest in this field

«One prick and then it´s done»: a mixed-methods exploratory study on intramuscular injection in heroin-assisted treatment

Background Intramuscular (IM) injection of drugs is associated with high rates of injecting-related injuries and diseases. However, little is known about the role of this route of administration in heroin-assisted treatment. The aim of this study was to determine the prevalence of IM diacetylmorphine administration and associated complications as well as to explore patients’ views and opinions on the topic and the underlying reasons for this practice. Methods The research site was a Swiss outpatient treatment centre specialised in heroin-assisted treatment. We conducted in-depth interviews with two patients who intramuscularly inject diacetylmorphine. Interviews were analysed qualitatively, and emerging themes were used to develop a 38-item questionnaire on IM injections. We then offered this questionnaire to all patients in the treatment centre. Results Five main themes emerged from the in-depth interviews: poor venous access, side effects, subjective effects, procedure for IM injection, and consideration of alternatives to IM. These themes covered the rationale for using this route of administration, complications, subjective effects of IM diacetylmorphine, hygiene and safety measures as well as alternative routes of administration. Fifty-three patients filled in the questionnaire. The lifetime prevalence of IM injections was 60.4% (n = 32) and 34.4% (n = 11) of the patients stated that IM injection was their primary route of administration. No participant reported using the IM route for street drugs. The main reason for IM injections was poor vein access. Other reasons given were time saving and less risk of injuries. Complications included induration of muscle tissue and pain, whereas more severe complications like thrombosis and infections of the injection site were reported much less often. Conclusion As the population of opioid-dependent individuals is aging and the deterioration of access veins is likely to increase, the frequency of IM injecting will equally increase. Even though our data show that the IM injection of diacetylmorphine in a clinical setting is a common practice and appears to be relatively safe, research on alternative routes of administration is needed to provide potentially less harmful alternative routes of administration in heroin-assisted treatment

Methylphenidate for Attention-Deficit and Hyperactivity Disorder in Adult Patients With Substance Use Disorders: Good Clinical Practice

Attention-deficit and hyperactivity disorder (ADHD) is a widespread neurodevelopmental disorder in children and adolescents, persisting into adulthood in a majority of them. ADHD and substance use disorders (SUDs) commonly co-occur in the clinical adult population. The higher-than-normal prevalence rates of SUDs in people with ADHD indicate increased risk for developing SUD. This narrative review deals with the question of whether or not adults with both disorders should be treated with methylphenidate (MPH), addressing specific issues surrounding this form of treatment. MPH is considered as first-line pharmacotherapy for ADHD. However, because of its stimulant-like reinforcing properties, MPH has a significant addictive potential to which persons with SUDs are especially susceptible. Appropriate treatment is therefore complex. Because of concerns about misuse and diversion of MPH medication, clinicians may be reluctant to use MPH to manage ADHD symptoms in these patients. However, it is essential to diagnose and treat ADHD adequately as appropriate therapy reduces the impairments, as well as the risk of developing comorbid disorders and poor treatment response. MPH should not be deprived of these patients because of the risk for misuse, especially as several strategies can be applied to minimize this risk. To conclude, carefully applied guideline-based diagnostics to clarify the potential presence of ADHD as well as a responsible prescription practice in a well-defined therapeutic setting with reliable monitoring of medication intake and regular consultations are essential conditions for a safe and proficient MPH treatment of ADHD in patients with SUD

Experiences with take-home dosing in heroin-assisted treatment in Switzerland during the COVID-19 pandemic–Is an update of legal restrictions warranted?

Heroin-assisted treatment comprises the use of diacetylmorphine (pharmaceutical heroin) for individuals with severe opioid use disorder. In Switzerland, take-home doses in heroin-assisted treatment are more strictly regulated as compared to conventional opioid agonist treatment. In light of the COVID-19 pandemic, the Swiss Federal Council provisionally adapted its policy, allowing for longer prescriptions of take-home diacetylmorphine. Before the beginning of the pandemic, take-home doses only occurred in exceptional circumstances and under strict criteria for patient eligibility. Following the legislative adaptations, we critically revised our internal centre policies as well. We report our experiences with oral take-home diacetylmorphine from a Swiss outpatient university centre specialising in heroin-assisted treatment. An additional 45 patients received take-home doses following the first lockdown. While some patients wished to return to their previous treatment regimen, most patients managed their medication well and showed good adherence. We also noticed an increase of treatment admissions that are likely related to the relaxed regulations. Previously, the strict therapeutic framework of visiting a HAT centre twice a day for supervised dispensing seemed to have discouraged these individuals from seeking medical treatment. From a medical point of view, the politically driven restrictions on take-home doses in heroin-assisted treatment are questionable and do not support the goal of harm reduction

Novel Medication Supply Model Guarantees Adequate Management and High Adherence to Polypharmacy in Older Opioid Users – Preliminary Results with Outpatients

Background: Life expectancy of older drug users has increased, primarily thanks to opioid agonist treatment (OAT). Nursing homes are often not adapted to accommodate patients with substance use disorders. Although care and adherence to polypharmacy in older opioid users need considerable resources e.g., daily visits to an outpatient clinic, outpatient treatment and surveillance are provided as long as possible. We developed a novel medication supply model with an electronic dispenser of pre-packed medications located at patient home, after allowing for law requirements concerning the dispensing of opioids, and present preliminary results from three illustrative outpatients. Methods: The community pharmacy provided unit-of-dose pouches with all solid oral medications directly to patient home. Opioids for substitution were obtained at the addiction clinic in at least weekly intervals, otherwise in the pouches. The pouches were loaded into a lockable, remote-controlled medication management aid that was programmed according to the patient’s medication schedule. The dispenser reminds patients with acoustic alerts to take their medication and records dates and times of medication retrievals. It automatically sends an alert if a patient misses to retrieve a dose. Results: Our three outpatients used the electronic dispenser during 659, 118 and 61 days, with a total of 5, 9, and 18 pills to take daily at 1, 3 and 5 intake times, respectively. The majority of the doses were taken on the preset time (94%, 68.2% and 73.7%) or deliberately in advance (pocket dose). Clinical benefits were initiation and maintenance of a therapy for dementia over 18 months and suppression of HIV viral load over 1.8 years (patient 1), prevention of further dose escalation of pain medication (patient 2) and release of prompts to initiate the existential task of cooking (patient 3). Conclusion: Our novel supply model allows adequate implementation and persistence of complex treatments with outpatients. Clinical outcomes improved, patients and caregivers were satisfied, and resources were saved

Valence band photoemission from the GaN(0001) surface

A detailed investigation by one-step photoemission calculations of the GaN(0001)-(1x1) surface in comparison with recent experiments is presented in order to clarify its structural properties and electronic structure. The discussion of normal and off-normal spectra reveals through the identified surface states clear fingerprints for the applicability of a surface model proposed by Smith et al. Especially the predicted metallic bonds are confirmed. In the context of direct transitions the calculated spectra allow to determine the valence band width and to argue in favor of one of two theoretical bulk band structures. Furthermore a commonly used experimental method to fix the valence band maximum is critically tested.Comment: 8 pages, 11 eps files, submitted to PR

Exploring why patients in heroin-assisted treatment are getting incarcerated - a qualitative study

Background: Heroin-assisted treatment has proven effective in reducing criminal offenses in opioid dependent individuals. Few studies attempted to explain the observed crime reduction and the reasons why these patients keep offending and getting incarcerated have to date not been explored. Methods: Patients with a history of incarcerations during the time of participating in heroin-assisted treatment (n = 22) were invited to a semi-structured, narrative interview. Findings were evaluated with Mayring's qualitative content analysis framework. Additionally, the Montreal Cognitive Assessment test and the multiple-choice vocabulary intelligence test used to assess cognitive impairment and premorbid intelligence levels. Results: Three main categories emerged in patients' narratives on their incarcerations: cocaine use, impaired functioning, and financial constraints. Lifetime prevalence of cocaine use disorder was 95.5% and their cocaine use often led to patients getting incarcerated. Impaired functioning mainly constituted the inability to receive and open mail. Financial constraints led to incarcerations in lieu of payment in 16 participants (72.7%). Categories overlapped notably and often occurred in close temporal proximity. A fourth category on the likelihood of getting incarcerated again in the future was inhomogeneous and ranged from the strong conviction to complete rejection of the scenario. Average premorbid intelligence levels were found, whereas the cognitive assessment suggested severe cognitive impairment in our sample. Conclusion: Participants mainly reported to have committed minor offenses and not being able to pay for resulting fines. The resulting prison sentences are an unconvincing practice from a medical and economic perspective alike. Public expenditure and the interruptions of the continuum of care could be reduced by legislatively protecting these marginalised patients