A progressively wetter climate in southern East Africa over the past 1.3 million years.

African climate is generally considered to have evolved towards progressively drier conditions over the past few million years, with increased variability as glacial-interglacial change intensified worldwide. Palaeoclimate records derived mainly from northern Africa exhibit a 100,000-year (eccentricity) cycle overprinted on a pronounced 20,000-year (precession) beat, driven by orbital forcing of summer insolation, global ice volume and long-lived atmospheric greenhouse gases. Here we present a 1.3-million-year-long climate history from the Lake Malawi basin (10°-14° S in eastern Africa), which displays strong 100,000-year (eccentricity) cycles of temperature and rainfall following the Mid-Pleistocene Transition around 900,000 years ago. Interglacial periods were relatively warm and moist, while ice ages were cool and dry. The Malawi record shows limited evidence for precessional variability, which we attribute to the opposing effects of austral summer insolation and the temporal/spatial pattern of sea surface temperature in the Indian Ocean. The temperature history of the Malawi basin, at least for the past 500,000 years, strongly resembles past changes in atmospheric carbon dioxide and terrigenous dust flux in the tropical Pacific Ocean, but not in global ice volume. Climate in this sector of eastern Africa (unlike northern Africa) evolved from a predominantly arid environment with high-frequency variability to generally wetter conditions with more prolonged wet and dry intervals.

Brain Activity Tracks Population Information Sharing by Capturing Consensus Judgments of Value.

Information that is shared widely can profoundly shape society. Evidence from neuroimaging suggests that activity in the ventromedial prefrontal cortex (vmPFC), a core region of the brain's valuation system tracks with this sharing. However, the mechanisms linking vmPFC responses in individuals to population behavior are still unclear. We used a multilevel brain-as-predictor approach to address this gap, finding that individual differences in how closely vmPFC activity corresponded with population news article sharing related to how closely its activity tracked with social consensus about article value. Moreover, how closely vmPFC activity corresponded with population behavior was linked to daily life news experience: frequent news readers tended to show high vmPFC across all articles, whereas infrequent readers showed high vmPFC only to articles that were more broadly valued and heavily shared. Using functional connectivity analyses, we found that superior tracking of consensus value was related to decreased connectivity of vmPFC with a dorsolateral PFC region associated with controlled processing. Taken together, our results demonstrate variability in the brain's capacity to track crowd wisdom about information value, and suggest (lower levels of) stimulus experience and vmPFC-dlPFC connectivity as psychological and neural sources of this variability.

Cognitive regulation of ventromedial prefrontal activity evokes lasting change in the perceived self-relevance of persuasive messaging.

Persuasive messages can change people's thoughts, feelings, and actions, but these effects depend on how people think about and appraise the meaning of these messages. Drawing from research on the cognitive control of emotion, we used neuroimaging to investigate neural mechanisms underlying cognitive regulation of the affective and persuasive impact of advertisements communicating the risks of binge drinking, a significant public health problem. Using cognitive control to up-regulate (vs. down-regulate) responses to the ads increased: negative affect related to consequences of excessive drinking, perceived ad effectiveness, and ratings of ad self-relevance made after a one-hour delay. Neurally, these effects of cognitive control were mediated by goal-congruent modulation of ventromedial prefrontal cortex and distributed brain patterns associated with negative emotion and subjective valuation. These findings suggest that people can leverage cognitive control resources to deliberately shape responses to persuasive appeals, and identify mechanisms of emotional reactivity and integrative valuation that underlie this ability. Specifically, brain valuation pattern expression mediated the effect of cognitive goals on perceived message self-relevance, suggesting a role for the brain's valuation system in shaping responses to persuasive appeals in a manner that persists over time.

Prognostic factors for and pattern of lymph-node involvement in patients with operable cervical cancer.

PURPOSE: Lymph node metastases significantly worsen the prognosis in cervical carcinoma. Risk factors-pathological and patient related-could select patients at high risk for lymph node involvement. METHODS: This retrospective analysis was performed by analyzing data from patients with cervical carcinoma treated between 2000 and 2017 at the Department of Obstetrics and Gynecology of the University Hospital Ulm. RESULTS: In total, 261 patients with cervical carcinoma (International Federation of Gynecology and Obstetrics (FIGO) stage IA-IIB) and lymphadenectomy with at least 10 removed lymph nodes were available for analysis. Overall, 86 (33.0%) patients had lymph node metastases; 73 patients had pelvic lymph node metastases only and 13 patients had both pelvic and paraaortic lymph node metastases. Lymph node metastases were found most often in the region of the external iliac artery and obturator fossa, with 57.0% and 54.7% of all 86 node-positive patients, respectively. Univariable analyses showed that presence of lymph node metastases was significantly associated with both preoperative FIGO stage (p = 0.001) and final pathological tumor stage (p < 0.001), status of resection margin (p = 0.002), lymphovascular space invasion (LVSI), (p < 0.001) and vascular space invasion, (p < 0.001). In a multivariable logistic regression model with presence of lymph node metastases (yes/no) as binary response variable, only LVSI (p < 0.001) and body mass index (BMI), (p = 0.035) remained as significant independent predictors of lymph node involvement. Subgroup analyses showed that LVSI was a significant predictive factor for lymph node involvement in patients with a preoperatively assessed FIGO stage < IIB (p < 0.001), but not for patients with a preoperatively assessed FIGO stage ≥ IIB (p = 0.122). CONCLUSIONS: The risk factor LVSI should play an important role in deciding whether an individualized therapy concept is based on escalating or deescalating treatment. In future, the sentinel concept could reduce morbidity and at the same time provide an important prognostic assessment for a subset of cervical cancer patients.

Rare compound heterozygous variants in PNKP identified by whole exome sequencing in a German patient with ataxia-oculomotor apraxia 4 and pilocytic astrocytoma.

Ataxia-oculomotor apraxia type 4 (AOA4) is a rare autosomal recessive neurologic disorder. The phenotype is characterized by ataxia, oculomotor apraxia, peripheral neuropathy and dystonia. AOA4 is caused by biallelic pathogenic variants in the PNKP gene encoding a polynucleotide kinase 3'-phosphatase with an important function in DNA-damage repair. By whole exome sequencing, we identified 2 variants within the PNKP gene in a 27-year-old German woman with a clinical AOA phenotype combined with a cerebellar pilocytic astrocytoma diagnosed at 23 years of age. One variant, a duplication in exon 14 resulting in the frameshift c.1253_1269dup p.(Thr424fs*49), has previously been described as pathogenic, for example, in cases of AOA4. The second variant, representing a nonsense mutation in exon 17, c.1545C>G p.(Tyr515*), has not yet been described and is predicted to cause a loss of the 7 C-terminal amino acids. This is the first description of AOA4 in a patient with central European descent. Furthermore, the occurrence of a pilocytic astrocytoma has not been described before in an AOA4 patient. Our data demonstrate compound heterozygous PNKP germline variants in a German patient with AOA4 and provide evidence for a possible link with tumor predisposition. Localization of the 2 variants in human PNKP NP_009185.2. NM_007254.3:c.1253_1269dup p.(Thr424fs*49) is predicted to cause a frameshift within the kinase domain, NM_007254.3:c.1545C>G p.(Tyr515*) is predicted to cause loss of 2 C-terminal amino acids of the kinase domain and 5 additional C-terminal amino acids.

Clinical implications of fracture-associated vascular damage in extremity and pelvic trauma.

BACKGROUND: Vascular damage in polytrauma patients is associated with high mortality and morbidity. Therefore, specific clinical implications of vascular damage with fractures in major trauma patients are reassessed. METHODS: This comprehensive nine-year retrospective single center cohort study analyzed demography, laboratory, treatment and outcome data from 3689 patients, 64 patients with fracture-associated vascular injuries were identified and were compared to a control group. RESULTS: Vascular damage occurred in 7% of patients with upper and lower limb and pelvic fractures admitted to the trauma room. Overall survival was 80% in pelvic fracture and 97% in extremity fracture patients and comparable to non-vascular trauma patients. Additional arterial damage required substantial fluid administration and was visible as significantly anemia and disturbed coagulation tests upon admission. Open procedures were done in over 80% of peripheral extremity vascular damage. Endovascular procedures were predominant (87%) in pelvic injury. CONCLUSION: Vascular damage is associated with high mortality rates especially in combination with pelvic fractures. Initial anemia, disturbed coagulation tests and the need for extensive pre-clinical fluid substitution were observed in the cohort with vascular damage. Therefore, fast diagnosis and early interventional and surgical procedures are necessary to optimize patient-specific outcome.

Allelic variation in CRHR1 predisposes to panic disorder: evidence for biased fear processing.

Corticotropin-releasing hormone (CRH) is a major regulator of the hypothalamic-pituitary-adrenal axis. Binding to its receptor CRHR1 triggers the downstream release of the stress response-regulating hormone cortisol. Biochemical, behavioral and genetic studies revealed CRHR1 as a possible candidate gene for mood and anxiety disorders. Here we aimed to evaluate CRHR1 as a risk factor for panic disorder (PD). Allelic variation of CRHR1 was captured by 9 single-nucleotide polymorphisms (SNPs), which were genotyped in 531 matched case/control pairs. Four SNPs were found to be associated with PD, in at least one sub-sample. The minor allele of rs17689918 was found to significantly increase risk for PD in females after Bonferroni correction and furthermore decreased CRHR1 mRNA expression in human forebrains and amygdalae. When investigating neural correlates underlying this association in patients with PD using functional magnetic resonance imaging, risk allele carriers of rs17689918 showed aberrant differential conditioning predominantly in the bilateral prefrontal cortex and safety signal processing in the amygdalae, arguing for predominant generalization of fear and hence anxious apprehension. Additionally, the risk allele of rs17689918 led to less flight behavior during fear-provoking situations but rather increased anxious apprehension and went along with increased anxiety sensitivity. Thus reduced gene expression driven by CRHR1 risk allele leads to a phenotype characterized by fear sensitization and hence sustained fear. These results strengthen the role of CRHR1 in PD and clarify the mechanisms by which genetic variation in CRHR1 is linked to this disorder.

Adverse events of group psychotherapy in the in-patient setting - results of a naturalistic trial.

OBJECTIVE: Adverse events of psychotherapy have often been neglected in research. In this study, potential adverse events of group psychotherapies in a psychiatric hospital were systematically assessed, explored for predictors and linked to treatment outcome. METHOD: A naturalistic trial was conducted in 180 in-patients attending different group psychotherapies. Adverse events were assessed using three different measures: (i) weekly reporting of unwanted treatment reactions, (ii) mood changes in response to every single group session and (iii) premature group termination. RESULTS: Different measures of adverse events were weakly associated. Deterioration of mood state and/or unwanted treatment reactions were experienced by 60-65% of all patients. Reports of unwanted treatment reactions decreased over time and were negatively associated with symptom improvement. However, mood state deterioration was constant and unrelated to treatment outcome. The rate of premature group termination was 34%. Significant predictors of adverse events included patient characteristics as well as disadvantageous group conditions. CONCLUSIONS: For the majority of patients, group psychotherapy in the in-patient setting is associated with adverse events. Changes over time and a strong correlation with general symptom severity must be considered in the assessment and interpretation of adverse events. Predictors should be considered as potential risk factors in future research.

A comparative study of Cutibacterium (Propionibacterium) acnes clones from acne patients and healthy controls.

BACKGROUND: Cutibacterium (Propionibacterium) acnes is assumed to play an important role in the pathogenesis of acne. OBJECTIVES: To examine if clones with distinct virulence properties are associated with acne. METHODS: Multiple C. acnes isolates from follicles and surface skin of patients with moderate to severe acne and healthy controls were characterized by multilocus sequence typing. To determine if CC18 isolates from acne patients differ from those of controls in the possession of virulence genes or lack of genes conducive to a harmonious coexistence the full genomes of dominating CC18 follicular clones from six patients and five controls were sequenced. RESULTS: Individuals carried one to ten clones simultaneously. The dominating C. acnes clones in follicles from acne patients were exclusively from the phylogenetic clade I-1a and all belonged to clonal complex CC18 with the exception of one patient dominated by the worldwide-disseminated and often antibiotic resistant clone ST3. The clonal composition of healthy follicles showed a more heterogeneous pattern with follicles dominated by clones representing the phylogenetic clades I-1a, I-1b, I-2 and II. Comparison of follicular CC18 gene contents, allelic versions of putative virulence genes and their promoter regions, and 54 variable-length intragenic and inter-genic homopolymeric tracts showed extensive conservation and no difference associated with the clinical origin of isolates. CONCLUSIONS: The study supports that C. acnes strains from clonal complex CC18 and the often antibiotic resistant clone ST3 are associated with acne and suggests that susceptibility of the host rather than differences within these clones may determine the clinical outcome of colonization.

Randomised phase III trial of FEC120 vs EC-docetaxel in patients with high-risk node-positive primary breast cancer: final survival analysis of the ADEBAR study.

BACKGROUND: Taxane-containing adjuvant chemotherapy has been established as standard treatment in node-positive breast cancer. This study compared efficacy and tolerability of epirubicin (E)/cyclophosphamide (C) followed by docetaxel (Doc) with a dose-dense 5-fluorouracil (F)+E+ C regimen. METHODS: The ADEBAR study was a randomised phase III trial for women with primary invasive breast cancer and ⩾4 metastatic axillary lymph nodes (n=1364). Treatment consisted of four 21-day cycles of E plus C, followed by four 21-day cycles of Doc (EC-Doc), or six 28-day cycles of E plus F plus C (FEC120). RESULTS: Disease-free survival (DFS) was similar in the two treatment arms as shown by multivariate Cox regression adjusted for other prognostic factors (EC-Doc vs FEC120, hazard ratio (HR): 1.087; 95% confidence interval (CI): 0.878-1.346, P=0.444). In addition, there was no significant difference in overall survival (OS) between the two groups (HR: 0.974; 95% CI: 0.750-1.264, P=0.841). Haematologic toxicity was more common in FEC120 recipients; non-haematologic toxicities occurred more frequently in the EC-Doc arm. The serious adverse event rate was significantly higher in the FEC120 group (29.7% vs 22.5%). CONCLUSIONS: EC-Doc provides a feasible and effective alternative therapy option to FEC120 with a different safety profile in this high-risk breast cancer cohort.

[Influences on Placental Growth Factor (PlGF) and Soluble fms-like Tyrosine Kinase-1 (sFlt-1) Concentration Levels at the Time of First Trimester Screening]. / Einflussfaktoren auf die placental growth factor (PlGF) und soluble fms-like tyrosine kinase-1 (sFlt-1) Konzentration im Rahmen des Erst-Trimester-Screenings.

INTRODUCTION: The angiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are significantly altered in preeclampsia with elevated sFlt-1 levels and low PlGF in the continuation of pregnancies. Furthermore, patients with preeclampsia reveal significantly low PlGF levels in the first trimester. MATERIAL AND METHOD: We performed a retrospective study including 161 patients during the first trimester screening between 11+0 and 13+6 weeks of gestation. In addition, we analyzed sFlt-1 und PlGF in maternal serum with a Roche Elecsys(®) System. RESULTS: The mean values for sFlt-1 were 1 247,11±545,84 pg/ml and 47,00±22,62 pg/ml for PlGF. There is a positive correlation between sFlt-1 and PAPP-A MoM (rS=0,681, p<0,001), and PlGF and PAPP-A MoM (rS=0,465, p<0,001), respectively. There was a negative correlation between sFlt-1 and maternal body mass index (rS=-0,225, p=0,005). Overweight patients had significantly lower sFlt-1 values than patients with normal weight (p=0,003). PlGF and the crown-rump-length of the fetus showed a positive correlation (rS=0,27, p<0,001), whereas PlGF and the Pulsatility Index of the uterine arteries were negative correlated (rS=-0,235; p=0,012). Patients with a preexistent diabetes mellitus had significantly low sFlt-1 und PlGF (p<0,05) values. Smokers had significantly elevated PlGF-values (p<0,001). CONCLUSION: sFlt-1 and PlGF are influenced by various factors during the first trimester of pregnancy which can be relevant for correct interpretation. Further prospective studies may be necessary to validate our results. The aim should be to establish sFlt-1 and PlGF MoM values to allow for integration into a screening for preeclampsia in the first trimester.

Impact of prior treatment on outcome of transformed follicular lymphoma and relapsed de novo diffuse large B cell lymphoma: a retrospective multicentre analysis.

Transformation of follicular lymphoma (FL) into aggressive disease and relapse of de novo diffuse large B cell lymphoma (DLBCL) are considered highly unfavourable events. However, most published data were acquired when rituximab was not routinely used. We retrospectively analysed 50 patients with transformed FL (tFL) in a multicenter study and compared them to 50 individuals with relapsed DLBCL (rDLBCL) who all obtained rituximab for the treatment of their disease. Our goal was to identify factors that predict a more favourable prognosis. After a median follow-up of 5.4 years from diagnosis, there was no significant difference in median overall survival (OS) from the date of transformation (tFL) or date of the first relapse (rDLBCL) (1.9 versus 3.9 years, P = .542). Of note, 5-year OS of patients with tFL was 46 %. Follicular lymphoma patients, treatment naïve prior to transformation, fared significantly better than pretreated patients (median not reached versus 1.4 years, P = .014). Regarding rDLBCL, female gender (13.9 versus 1.8 years, P = .019) and absence of rituximab prior to the first relapse (14.0 versus 1.8 years, P = .035) were favourable prognostic factors in a uni- and multivariate analysis. Only a proportion of patients received high-dose chemotherapy with autologous stem cell transplantation (HDT-ASCT), i.e. 38 and 52 % of patients with tFL and rDLBCL, respectively. Our data indicate that a favourable prognosis is conferred by treatment naivety in tFL and by rituximab naivety in rDLBCL. In contrast, we did not find a prognostic impact of HDT-ASCT in our series.

Adjuvant therapeutic decisions in elderly breast cancer patients: the role of chemotherapy in a retrospective analysis.

PURPOSE: Decisions on the type of adjuvant treatment in older breast cancer patients are challenging. Side effects of chemotherapy have to be weighed against life expectancy, comorbidities, functional status, and frailty on the basis of studies usually excluding patients over 69 years. To aid this decision, we analyzed a database of 6000 unselected patients and of those evaluated elderly primary breast cancer patients with hormone receptor-negative tumors from 1963 until 2003 in respect of survival data depending on adjuvant treatment. METHODS: A total of 131 elderly (i.e., >65 years) patients were observed retrospectively for a median of 72 months. Patients received breast-conserving therapy or mastectomy and adjuvant radiotherapy, chemotherapy, and endocrine therapy. Data were collected from a hospital-intern database. RESULTS: Median age at diagnosis was 72 years. Mostly, tumors were small (81 % T1, 17 % T2) but of unfavorable grading (40 % G2, 35 % G3). Lymph nodes were positive in 42 %. Mastectomy was performed in 65 %. While 42 % of patients received radiotherapy, only 10 % were treated with chemotherapy. Patients with G2 and G3 tumors (p = 0.027), younger women (p = 0.012), and patients with positive lymph node status (p < 0.0001) more likely received chemotherapy. Recurrence-free survival was longer in patients without chemotherapy (37 vs. 29 months, p = 0.234). Overall survival was non-significantly shorter in patients who received chemotherapy (59 vs. 81 months, p = 0.131). CONCLUSIONS: In this analysis, adjuvant chemotherapy was not associated with improved survival, presumably caused by an a priori poor prognosis of these patients. For an aging society more data are urgently needed to help selecting and personalizing adjuvant treatment within subgroups of breast cancer in older women.

Diagnosing attention-deficit hyperactivity disorder (ADHD) in children involved with child protection services: are current diagnostic guidelines acceptable for vulnerable populations?

Children involved with child protection services (CPS) are diagnosed and treated for attention-deficit hyperactivity disorder (ADHD) at higher rates than the general population. Children with maltreatment histories are much more likely to have other factors contributing to behavioural and attentional regulation difficulties that may overlap with or mimic ADHD-like symptoms, including language and learning problems, post-traumatic stress disorder, attachment difficulties, mood disorders and anxiety disorders. A higher number of children in the child welfare system are diagnosed with ADHD and provided with psychotropic medications under a group care setting compared with family-based, foster care and kinship care settings. However, children's behavioural trajectories change over time while in care. A reassessment in the approach to ADHD-like symptoms in children exposed to confirmed (or suspected) maltreatment (e.g. neglect, abuse) is required. Diagnosis should be conducted within a multidisciplinary team and practice guidelines regarding ADHD diagnostic and management practices for children in CPS care are warranted both in the USA and in Canada. Increased education for caregivers, teachers and child welfare staff on the effects of maltreatment and often perplexing relationship with ADHD-like symptoms and co-morbid disorders is also necessary. Increased partnerships are needed to ensure the mental well-being of children with child protection involvement.

Transformation and additional malignancies are leading risk factors for an adverse course of disease in marginal zone lymphoma.

BACKGROUND: Marginal zone lymphoma (MZL) is a non-Hodgkin lymphoma that occurs as extra nodal, nodal, or splenic. While MZL is generally considered an indolent disease, a substantial percentage of patients follow an unfavorable course. The objective of this retrospective analysis was to identify predictors for a reduced overall survival (OS), or conversely an increased OS. PATIENTS AND METHODS: One hundred and ninety-seven MZL patients were analyzed. Apart from assessing previously published risk factors, concomitant morbidity at diagnosis, transformation into aggressive lymphoma, and occurrence of additional malignancies were evaluated. RESULTS: Next to the known risk factors, i.e. above 60 years of age and elevated serum lactate dehydrogenase (LDH), we demonstrate that transformation into aggressive lymphoma, as well as additional malignancies, are important independent risk factors for a shortened OS in a multivariate analysis, irrespective of the MZL localization. Impressively, in the group of patients lacking LDH elevation, transformation, and/or additional malignancies, only 1 of 63 patients died during follow-up compared with 37 of 87 patients in the high-risk group (HR = 22.8; 95% confidence interval 3.1-167.0; P = 0.002). CONCLUSIONS: Our analysis proposes novel risk factors and warrants for a continuous follow-up to detect the occurrence of transformation and additional malignancies early on.

Radioimmunotherapy for first-line and relapse treatment of aggressive B-cell non-Hodgkin lymphoma: an analysis of 215 patients registered in the international RIT-Network.

PURPOSE: Very few reliable clinical data about the use of radioimmunotherapy in aggressive B-cell lymphoma exist. METHODS: Patients with aggressive B-cell lymphoma registered in the international RIT-Network were analysed with regard to prior treatment, response and side effects. The RIT-Network is a web-based registry that collects observational data from radioimmunotherapy-treated patients with malignant lymphoma across 13 countries. RESULTS: This analysis included 215 with aggressive B-cell lymphoma out of 232 patients registered in the RIT-Network. Histological subtypes were as follows: 190 diffuse large B-cell, 15 primary mediastinal, 9 anaplastic large cell, and 1 intravascular lymphoma. The median age of the patients was 62 years (range 17 - 88), with 27% above the age of 70 years. Radioimmunotherapy was mainly used as consolidation after first-line or second-line chemotherapy (56.1%), as part of third-line to eighth-line therapy for relapse (16.4%), and in refractory disease (12.2%). Grade IV neutropenia and thrombopenia and grade III anaemia were observed. The median time to recovery of blood count was 81 days (range 0 - 600 days). The overall response rate was 63.3%. The complete response rate was 76.4 % in patients treated as part of first-line therapy, and 44.3% in patients with relapse. Mean overall survival in first-line therapy patients was 32.7 months and 14.0 months in patients with relapse or refractory disease, respectively. CONCLUSION: Most patients with aggressive B-cell lymphoma in the RIT-Network received radioimmunotherapy as consolidation after first-line therapy with excellent complete remission and overall survival rates compared to published data. In relapsed aggressive B-cell lymphoma, radioimmunotherapy is a safe and feasible treatment leading to satisfactory response rates with acceptable toxicity.

The effect of self-management techniques on relevant outcomes in chronic low back pain: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Among many treatment approaches for chronic low back pain (CLBP), self-management techniques are becoming increasingly important. The aim of this paper was to (a) provide an overview of existing digital self-help interventions for CLBP and (b) examine the effect of these interventions in reducing pain intensity, pain catastrophizing and pain disability. DATABASES AND DATA TREATMENT: Following the PRISMA guideline, a systematic literature search was conducted in the MEDLINE, EMBASE, PsychInfo, CINAHL and Cochrane databases. We included randomized controlled trials from the last 10 years that examined the impact of digital self-management interventions on at least one of the three outcomes in adult patients with CLBP (duration ≥3 months). The meta-analysis was based on random-effects models. Standardized tools were used to assess the risk of bias (RoB) for each study and the quality of evidence for each outcome. RESULTS: We included 12 studies (n = 1545). A small but robust and statistically significant pooled effect was found on pain intensity (g = 0.24; 95% CI [0.09, 0.40], k = 12) and pain disability (g = 0.43; 95% CI [0.27, 0.59], k = 11). The effect on pain catastrophizing was not significant (g = 0.38; 95% CI [-0.31, 1.06], k = 4). The overall effect size including all three outcomes was g = 0.33 (95% CI [0.21, 0.44], k = 27). The RoB of the included studies was mixed. The quality of evidence was moderate or high. CONCLUSION: In summary, we were able to substantiate recent evidence that digital self-management interventions are effective in the treatment of CLBP. Given the heterogeneity of interventions, further research should aim to investigate which patients benefit most from which approach. SIGNIFICANCE: This meta-analysis examines the effect of digital self-management techniques in patients with CLBP. The results add to the evidence that digital interventions can help patients reduce their pain intensity and disability. A minority of studies point towards the possibility that digital interventions can reduce pain catastrophizing. Future research should further explore which patients benefit most from these kinds of interventions.

Current treatment of mantle cell lymphoma: results of a national survey and consensus meeting.

In most patients, mantle cell lymphoma (MCL) shows an aggressive clinical course with a continuous relapse pattern and a median survival of only 3-5 years. In the current study generation of the European MCL Network, the addition of high-dose Ara-C to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)-like regimen followed by myeloablative consolidation achieved a significant improvement of progression-free survival in younger patients. In elderly patients, rituximab maintenance led to a marked prolongation of remission duration. Emerging strategies include mammalian target of rapamycin (mTOR) inhibitors, proteasome inhibitors, immune modulatory drugs, Bruton's tyrosine kinase inhibitors and others, all based on the dysregulated control of cell cycle machinery and impairment of several apoptotic pathways. Combination strategies are currently being investigated in numerous trials, but their introduction into clinical practice and current treatment algorithms remains a challenge. In the current survey, the application of the molecular targeted compounds were collected and evaluated by a representative national network of 14 haematological institutions. Optimised strategies are recommended for clinical routine. Future studies will apply individualised approaches according to the molecular risk profile of the patient.