Eemian landscape response to climatic shifts and evidence for northerly neanderthal occupation at a palaeolake margin in northern germany

The prevailing view suggests that the Eemian interglacial on the European Plain was characterized by largely negligible geomorphic activity beyond the coastal areas. However, systematic geomorphological studies are sparse. Here we present a detailed reconstruction of Eemian to Early Weichselian landscape evolution in the vicinity of a small fingerlake on the northern margin of the Salzwedel Palaeolake in Lower Saxony (Germany). We apply a combination of seismics, sediment coring, pollen analysis and luminescence dating on a complex sequence of colluvial, paludal and lacustrine sediments. Results suggest two pronounced phases of geomorphic activity, directly before the onset and at the end of the Eemian period, with an intermediate period of pronounced landscape stability. The dynamic phases were largely driven by incomplete vegetation cover, but likely accentuated by fluvial incision in the neighbouring Elbe Valley. Furthermore, we discovered Neanderthal occupation at the lakeshore during Eemian pollen zone (PZ) E IV, which is chronologically in line with other known Eemian sites of central Europe. Our highly‐resolved spatio‐temporal data substantially contribute to the understanding of climate‐induced geomorphic processes throughout and directly after the last interglacial period. It helps unraveling the landscape dynamics between the coastal areas to the north and the loess belt to the south

Eemian landscape response to climatic shifts and evidence for northerly Neanderthal occupation at a palaeolake margin in northern Germany

The prevailing view suggests that the Eemian interglacial on the European Plain was characterized by largely negligible geomorphic activity beyond the coastal areas. However, systematic geomorphological studies are sparse. Here we present a detailed reconstruction of Eemian to Early Weichselian landscape evolution in the vicinity of a small fingerlake on the northern margin of the Salzwedel Palaeolake in Lower Saxony (Germany). We apply a combination of seismics, sediment coring, pollen analysis and luminescence dating on a complex sequence of colluvial, paludal and lacustrine sediments. Results suggest two pronounced phases of geomorphic activity, directly before the onset and at the end of the Eemian period, with an intermediate period of pronounced landscape stability. The dynamic phases were largely driven by incomplete vegetation cover, but likely accentuated by fluvial incision in the neighbouring Elbe Valley. Furthermore, we discovered Neanderthal occupation at the lakeshore during Eemian pollen zone (PZ) E IV, which is chronologically in line with other known Eemian sites of central Europe. Our highly-resolved spatio-temporal data substantially contribute to the understanding of climate-induced geomorphic processes throughout and directly after the last interglacial period. It helps unraveling the landscape dynamics between the coastal areas to the north and the loess belt to the south

Testing for deficient mismatch repair and microsatellite instability : A focused update

Testing to detect mismatch repair deficiency (dMMR) and high-grade microsatellite instability (MSI-H) has become an integral part of the routine diagnostic workup for colorectal cancer (CRC). While MSI was initially considered to be a possible indicator of a hereditary disposition to cancer (Lynch syndrome, LS), today the prediction of the therapy response to immune checkpoint inhibitors (ICI) is in the foreground. Corresponding recommendations and testing algorithms are available for use in primary diagnosis (reviewed in: Rüschoff et al. 2021). Given the increasing importance for routine use and the expanding indication spectrum of ICI therapies for non-CRCs, such as endometrial, small intestinal, gastric, and biliary tract cancers, an updated review of dMMR/MSI testing is presented. The focus is on the challenges in the assessment of immunohistochemical stains and the value of PCR-based procedures, considering the expanded ICI indication spectrum. A practice-oriented flowchart for everyday diagnostic decision-making is provided that considers new data on the frequency and type of discordances between MMR-IHC and MSI-PCR findings, and the possible role of Next Generation Sequencing in clarifying them. Reference is made to the significance of systematic quality assurance measures (e.g., QuIP MSI portal and multicenter proficiency testing), including regular continued training and education. // Der Nachweis der Mismatch-Reparatur-Defizienz (dMMR) mit konsekutiver hochgradiger Mikrosatelliteninstabilität (MSI-H) ist inzwischen fester Bestandteil der Diagnostik des kolorektalen Karzinoms (KRK). Galt MSI anfänglich als möglicher Indikator einer erblichen Krebsdisposition (Lynch-Syndrom, LS) steht heute die Vorhersage des Therapieansprechens auf Immuncheckpoint-Inhibitoren (ICI) im Vordergrund. Entsprechende Empfehlungen und Testalgorithmen liegen für den Einsatz in der Primärdiagnostik vor (Übersicht in: Rüschoff et al. 2021). Aufgrund des damit verbundenen routinemäßigen Einsatzes und des sich erweiternden Indikationsspektrums von ICI-Therapien für Nicht-KRK wie Endometrium‑, Dünndarm‑, Magen- und Gallenwegskarzinome wird eine aktualisierte Übersicht zur dMMR/MSI-Testung vorgelegt. Fokus sind die Herausforderungen bei der Beurteilung immunhistochemischer Färbungen und die Wertigkeit PCR-basierter Verfahren unter Berücksichtigung des erweiterten ICI-Indikationsspektrums. Anhand neuer Daten zur Häufigkeit und Art von Diskordanzen zwischen dMMR- und MSI-Befund und der möglichen Rolle von Next Generation Sequencing zu deren Aufklärung wird ein praxisorientiertes Diagramm zur Entscheidungsfindung im diagnostischen Alltag vorgestellt. Wir weisen zudem auf die Bedeutung systematischer Qualitätssicherungsmaßnahmen (z. B. QuIP MSI-Portal und Ringversuche) einschließlich einer regelmäßigen Fortbildung hin

Colon cancer risk and different HRT formulations: a case-control study

<p>Abstract</p> <p>Background</p> <p>Most studies have found no increased risk of colon cancer associated with hormone replacement therapy (HRT), or even a decreased risk. But information about the effects of different HRT preparations is lacking.</p> <p>Methods</p> <p>A case-control study was performed within Germany in collaboration with regional cancer registries and tumor centers. Up to 5 controls were matched to each case of colon cancer. Conditional logistic regression analysis was applied to estimate crude and adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Stratified analyses were performed to get an impression of the risk associated with different estrogens and progestins.</p> <p>Results</p> <p>A total of 354 cases of colon cancer were compared with 1422 matched controls. The adjusted overall risk estimate for colon cancer (ColC) associated with ever-use of HRT was 0.97 (0.71 – 1.32). No clinically relevant trends for ColC risk were observed with increasing duration of HRT use, or increasing time since first or last HRT use in aggregate.</p> <p>Whereas the overall risk estimates were stable, the numbers in many of the sub-analyses of HRT preparation groups (estrogens and progestins) were too small for conclusions. Nevertheless, if the ColC risk estimates are taken at face value, most seemed to be reduced compared with never-use of HRT, but did not vary much across HRT formulation subgroups. In particular, no substantial difference in ColC risk was observed between HRT-containing conjugated equine estrogens (CEE) or medroxyprogesterone acetate (MPA) and other formulations more common in Europe.</p> <p>Conclusion</p> <p>Ever-use of HRT was not associated with an increased risk of colon cancer. In contrary, most risk estimates pointed non-significantly toward a lower ColC risk in HRT ever user. They did not vary markedly among different HRT formulations (estrogens, progestins). However, the small numbers and the overlapping nature of the subgroups suggest cautious interpretation.</p

Der Geologische Dienst in Sachsen: Festband zum Jubiläum 150 Jahre Landesgeologie

Der Geologische Dienst von Sachsen feiert im Jahr 2022 sein 150-jähriges Jubiläum – am 6. April 1872 wurde die Geologische Landesuntersuchung im Königreich Sachsen gegründet. Auf 153 Seiten der Reihe „Geoprofil“ werden Einblicke in die Arbeit des Geologischen Dienstes im LfULG, seinen Aufgaben und die Dienste als zuständige Fachbehörde gegeben. Die elf Einzelbeiträge zeigen die aktuellen Herausforderungen und Chancen, die sich aus den Themenbereichen Umwelt, Naturschutz und Geologie für Sachsen stellen. Im Einzelnen geht es in den Beiträgen um die sächsische Rohstoffstrategie, die Suche nach einem Endlagerstandort für radioaktive Abfälle, Erdwärme, Hydrogeologie, die Eisenbahn Neubaustrecke Dresden – Prag, Naturgefahren, das geowissenschaftliche Archiv, Träger öffentlicher Belange (TöB), Geoparks und einen Blick in die 150 jährige Geschichte. Redaktionsschluss: 30.11.202

Breast cancer risk associated with different HRT formulations: a register-based case-control study

BACKGROUND: Previous epidemiological studies have inconsistently shown a modestly increased breast cancer risk associated with hormone replacement therapy (HRT). Limited information is available about different formulations – particularly concerning different progestins. METHODS: A case-control study was performed within Germany in collaboration with regional cancer registries and tumor centers. Up to 5 controls were matched breast cancer cases. Conditional logistic regression analysis was applied to estimate crude and adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Stratified analyses were performed to compare the risk of different estrogens, progestins, and combinations. RESULTS: A total of 3593 cases of breast cancer were identified and compared with 9098 controls. The adjusted overall risk estimate for breast cancer (BC) associated with current or past use of HRT was 1.2 (1.1–1.3), and almost identical for lag times from 6 months to 6 years prior to diagnosis. No significant trend of increasing BC risk was found with increasing duration of HRT use, or time since first or last use in aggregate. Many established BC risk factors significantly modified the effect of HRT on BC risk, particularly first-degree family history of BC, higher age, lower education, higher body mass index (BMI), and never having used oral contraceptives (OCs) during lifetime. Whereas the overall risk estimates were stable, the numbers in many of the sub-analyses of HRT formulation groups (estrogens, progestins, and combinations) were too small for strong conclusions. Nevertheless, the BC risk seems not to vary much across HRT formulation subgroups. In particular, no substantial difference in BC risk was observed between HRT containing conjugated equine estrogens (CEE) or medroxyprogesterone acetate (MPA) and other formulations more common in Europe. CONCLUSION: The BC risk of HRT use is rather small. Low risk estimates for BC and a high potential for residual confounding and bias in this observational study do not permit causal conclusions. Apparently, there is not much variation of the BC risk across HRT formulations (estrogens, progestins). However, the small numbers and the overlapping nature of some of the subgroups suggest cautious interpretation

Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study

INTRODUCTION: Associations of hormone-receptor positive breast cancer with excess adiposity are reasonably well characterized; however, uncertainty remains regarding the association of body mass index (BMI) with hormone-receptor negative malignancies, and possible interactions by hormone replacement therapy (HRT) use. METHODS: Within the European EPIC cohort, Cox proportional hazards models were used to describe the relationship of BMI, waist and hip circumferences with risk of estrogen-receptor (ER) negative and progesterone-receptor (PR) negative (n = 1,021) and ER+PR+ (n = 3,586) breast tumors within five-year age bands. Among postmenopausal women, the joint effects of BMI and HRT use were analyzed. RESULTS: For risk of ER-PR- tumors, there was no association of BMI across the age bands. However, when analyses were restricted to postmenopausal HRT never users, a positive risk association with BMI (third versus first tertile HR = 1.47 (1.01 to 2.15)) was observed. BMI was inversely associated with ER+PR+ tumors among women aged ≤49 years (per 5 kg/m2 increase, HR = 0.79 (95%CI 0.68 to 0.91)), and positively associated with risk among women ≥65 years (HR = 1.25 (1.16 to 1.34)). Adjusting for BMI, waist and hip circumferences showed no further associations with risks of breast cancer subtypes. Current use of HRT was significantly associated with an increased risk of receptor-negative (HRT current use compared to HRT never use HR: 1.30 (1.05 to 1.62)) and positive tumors (HR: 1.74 (1.56 to 1.95)), although this risk increase was weaker for ER-PR- disease (Phet = 0.035). The association of HRT was significantly stronger in the leaner women (BMI ≤22.5 kg/m2) than for more overweight women (BMI ≥25.9 kg/m2) for, both, ER-PR- (HR: 1.74 (1.15 to 2.63)) and ER+PR+ (HR: 2.33 (1.84 to 2.92)) breast cancer and was not restricted to any particular HRT regime. CONCLUSIONS: An elevated BMI may be positively associated with risk of ER-PR- tumors among postmenopausal women who never used HRT. Furthermore, postmenopausal HRT users were at an increased risk of ER-PR- as well as ER+PR+ tumors, especially among leaner women. For hormone-receptor positive tumors, but not for hormone-receptor negative tumors, our study confirms an inverse association of risk with BMI among young women of premenopausal age. Our data provide evidence for a possible role of sex hormones in the etiology of hormone-receptor negative tumors

Interpretation Bias Across Body Dysmorphic, Social Anxiety and Generalized Anxiety Disorder—A Multilevel, Diffusion Model Account

Dietel FA, Möllmann A, Bürkner P-C, Wilhelm S, Buhlmann U. Interpretation Bias Across Body Dysmorphic, Social Anxiety and Generalized Anxiety Disorder—A Multilevel, Diffusion Model Account. Cognitive Therapy and Research. 2021;45(4):715-729.**Background** Interpretation biases are suggested to be transdiagnostic phenomena, but have rarely been compared across different disorders and current concerns. **Methods** We investigated explicit, decision-based, and more implicit, reaction time-based interpretation bias in individuals with body dysmorphic disorder (BDD;N = 29), social anxiety disorder (SAD;N = 36), generalized anxiety disorder (GAD;N = 22), and non-clinical controls (NC;N = 32), using an adapted Word Sentence Association Paradigm (WSAP). **Results** Results indicated that interpretation bias occurred transdiagnostically, while content-specific bias patterns varied meaningfully across groups. BDD and SAD shared explicit and, more inconsistently, implicit interpretation biases for appearance-related and social situations. The GAD group exhibited an explicit and implicit negative interpretation bias for general situations, and an additional implicit lack of positive bias. Mechanistic Wiener diffusion model analyses revealed that interpretation bias patterns were mainly driven by speeded information uptake, potentially mirroring disorder-specific associative memory organization. **Conclusions** These findings have important implications for understanding interpretation biases as both etiological and treatment factors

Internet-based interpretation bias modification for body dissatisfaction

Objective Appearance-related interpretation bias is postulated to play a role in the maintenance of body dissatisfaction (BD), a risk factor for body dysmorphic disorder (BDD), and eating disorders (ED). Cognitive bias modification for interpretation (CBM-I) has been shown to reduce maladaptive interpretation bias and symptoms in various emotional disorders. This study investigated the acceptability and efficacy of an easily disseminable, web-based CBM-I program for BD. Methods Individuals with high BD (N = 318) were randomized to a multi-session CBM-I (Sentence Word Association Paradigm [SWAP] with feedback) vs. control (SWAP without feedback) versus waitlist condition. Interpretation bias, BD and associated symptoms were assessed at baseline and post-intervention. Symptoms were monitored up to 1-week and 4-week follow-up. We further investigated transference effects to stress reactivity, as predicted by cognitive-behavioral models, at post-intervention. Results Appearance-related CBM-I led to a differential pre-post increase in adaptive interpretation patterns, particularly for appearance-related and social situations (d = 0.65-1.18). Both CBM-I and control training reduced BD, BDD symptom severity, and depression. However, CBM-I (vs. control and waitlist) improved appearance-related quality of life (d = 0.51), self-esteem (d = 0.52), and maladaptive appearance-related beliefs (d = 0.47). State stress reactivity was overall reduced in the CBM-I condition (vs. waitlist). Intervention effects largely held stable up to follow-ups. Treatment satisfaction was comparable to other CBM-I studies, with low rates of adverse reactions. Discussion These findings support assumptions of cognitive-behavioral models for BD, BDD, and ED, and suggest that web-based CBM-I is an efficacious and acceptable intervention option.Peer reviewe

Internet-based Interpretation Bias Modification for body dissatisfaction: A three-armed randomized controlled trial

Objective: Appearance-related interpretation bias is postulated to play a role in the maintenance of body dissatisfaction, a risk factor for body dysmorphic disorder (BDD) and eating disorders (ED). Cognitive Bias Modification for Interpretation (CBM-I) has been shown to reduce interpretation bias and symptoms in emotional disorders. This study investigated the acceptability and efficacy of web-based, appearance-related CBM-I for body dissatisfaction in a three-armed randomized controlled trial. Methods: Participants with high body dissatisfaction (N = 318) were randomized to multi-session CBM-I (Sentence Word Association Paradigm, SWAP, with feedback) vs. control (SWAP without feedback) vs. waitlist condition. Body dissatisfaction, BDD symptoms, self-esteem, depression and quality of life were assessed at baseline and post-intervention. Symptoms were monitored up to one-week and four-week follow up. We further investigated video-based stress reactivity at post-intervention. Results: CBM-I led to a differential pre-post increase in adaptive interpretation patterns, particularly for appearance-related and social situations (d = 0.65-1.18). Both CBM-I and control training reduced body dissatisfaction, BDD symptom severity and depression. However, CBM-I (vs. control and waitlist) improved appearance-related quality of life (d = 0.51), self-esteem (d = 0.52), and maladaptive appearance-related beliefs (d = 0.47). State stress reactivity was overall reduced in the CBM-I group (vs. waitlist). Intervention effects largely held stable up to follow-up. Treatment satisfaction for appearance-related CBM-I was comparable to other CBM-I studies, with overall low rates of adverse reactions. Discussion: These findings support assumptions of cognitive-behavioral models for body dissatisfaction, BDD and ED, and suggest that CBM-I is an efficacious and acceptable intervention