Omitting re-excision for focally positive margins after breast-conserving surgery does not impair disease-free and overall survival

Purpose: In contrast to other countries, the Dutch breast cancer guideline does not recommend re-excision for focally positive margins after breast-conserving surgery (BCS) in invasive tumor and does recommend whole-breast irradiation including boost. We investigated whether omitting re-excision as compared to performing re-excision affects prognosis with a retrospective population-based cohort study. Methods: The total cohort included 32,119 women with primary BCS for T1–T3 breast cancer diagnosed between 2003 and 2008 from the nationwide Netherlands cancer registry. The subcohort included 10,433 patients in whom the resection margins were registered. Outcome measures were 5-year ipsilateral breast tumor recurrence (IBTR) rate, 5-year disease-free survival (DFS) rate, and 10-year overall survival (OS) rate. Results: In the total cohort, 25,878 (80.6%) did not have re-excision, 2368 (7.4%) had re-excision by BCS, and 3873 (12.1%) had re-excision by mastectomy. Five-year IBTR rates were 2.1, 2.8, and 2.9%, respectively (p = 0.001). In the subcohort, 7820 (75.0%) had negative margins without re-excision, 492 (4.7%) had focally positive margins without re-excision, 586 (5.6%) had focally positive margins and underwent re-excision, and 1535 (14.7%) had extensively positive margins and underwent re-excision. Five-year IBTR rate was 2.3, 2.9, 1.1, and 2.9%, respectively (p = 0.099). Compared to omitting re-excision, performing re-excision for focally positive margins was associated with lower risk of IBTR (adjusted HR 0.30, 95% CI 0.11–0.82), but not with DFS (adjusted HR 0.83 95% CI 0.59–1.17) nor with OS (adjusted HR 1.17 95% CI 0.87–1.59). Conclusion: Omitting re-excision in breast cancer patients for focally positive margins after BCS does not impair DFS and OS, provided that whole-breast irradiation including boost is given

Ins and Outs of Cerebellar Modules

The modular concept of cerebellar connections has been advocated in the lifetime work of Jan Voogd. In this concept, a cerebellar module is defined as the conglomerate of one or multiple and non-adjacent, parasagittally arranged zones of Purkinje cells, their specific projection to a well-defined region of the cerebellar nuclei, and the climbing fiber input to these zones by a well-defined region of the inferior olivary complex. The modular organization of these olivo-cortico-nuclear connections is further exemplified by matching reciprocal connections between inferior olive and cerebellar nuclei. Because the different regions of the cerebellar nuclei show highly specific output patterns, cerebellar modules have been suggested to constitute functional entities. This idea is strengthened by the observation that anatomically defined modules adhere to the distribution of chemical markers in the cerebellar cortex suggesting that modules not only differ in their input and output relations but also may differ in operational capabilities. Here, I will briefly review some recent data on the establishment of cerebellar modules in rats. Furthermore, some evidence will be shown suggesting that the other main afferent system (i.e., mossy fibers), at least to some extent, also adheres to the modular organization. Finally, using retrograde transneuronal tracing with rabies virus, some evidence will be provided that several cerebellar modules may be involved in the control of individual muscles

Risk of cardiovascular events, arrhythmia and all-cause mortality associated with clarithromycin versus alternative antibiotics prescribed for respiratory tract infections: a retrospective cohort study

Objective: To determine whether treatment with clarithromycin for respiratory tract infections was associated with an increased risk of cardiovascular (CV) events, arrhythmias or all-cause mortality compared with other antibiotics. Design: Retrospective cohort design comparing clarithromycin monotherapy for lower (LRTI) or upper respiratory tract infection (URTI) with other antibiotic monotherapies for the same indication. Setting: Routine primary care data from the UK Clinical Practice Research Datalink and inpatient data from the Hospital Episode Statistics (HES). Participants: Patients aged ≥35 years prescribed antibiotic monotherapy for LRTI or URTI 1998–2012 and eligible for data linkage to HES. Main outcome measures: The main outcome measures were: adjusted risk of first-ever CV event, within 37 days of initiation, in commonly prescribed antibiotics compared with clarithromycin. Secondarily, adjusted 37-day risks of first-ever arrhythmia and allcause mortality. Results: Of 700 689 treatments for LRTI and eligible for the CV analysis, there were 2071 CV events (unadjusted event rate: 29.6 per 10 000 treatments). Of 691 998 eligible treatments for URTI, there were 688 CV events (9.9 per 10 000 treatments). In LRTI and URTI, there were no significant differences in CV risk between clarithromycin and all other antibiotics combined: OR=1.00 (95% CI 0.82 to 1.22) and 0.82 (0.54 to 1.25), respectively. Adjusted CV risk in LRTI versus clarithromycin ranged from OR=1.42 (cefalexin; 95% CI 1.08 to 1.86) to 0.92 (doxycycline; 0.64 to 1.32); in URTI, from 1.17 (co-amoxiclav; 0.68 to 2.01) to 0.67 (erythromycin; 0.40 to 1.11). Adjusted mortality risk versus clarithromycin in LRTI ranged from 0.42 to 1.32; in URTI, from 0.75 to 1.43. For arrhythmia, adjusted risks in LRTI ranged from 0.68 to 1.05; in URTI, from 0.70 to 1.22. Conclusions: CV events were more likely after LRTI than after URTI. When analysed by specific indication, CV risk associated with clarithromycin was no different to other antibiotics

Cerebellar Zones: A Personal History

Cerebellar zones were there, of course, before anyone noticed them. Their history is that of young people, unhindered by preconceived ideas, who followed up their observations with available or new techniques. In the 1960s of the last century, the circumstances were fortunate because three groups, in Leiden, Lund, and Bristol, using different approaches, stumbled on the same zonal pattern in the cerebellum of the cat. In Leiden, the Häggqvist myelin stain divulged the compartments in the cerebellar white matter that channel the afferent and efferent connections of the zones. In Lund, the spino-olivocerebellar pathways activated from individual spinal funiculi revealed the zonal pattern. In Bristol, charting the axon reflex of olivocerebellar climbing fibers on the surface of the cerebellum resulted in a very similar zonal map. The history of the zones is one of accidents and purposeful pursuit. The technicians, librarians, animal caretakers, students, secretaries, and medical illustrators who made it possible remain unnamed, but their contributions certainly should be acknowledged

Overexpression of P70 S6 kinase protein is associated with increased risk of locoregional recurrence in node-negative premenopausal early breast cancer patients

The RPS6KB1 gene is amplified and overexpressed in approximately 10% of breast carcinomas and has been found associated with poor prognosis. We studied the prognostic significance of P70 S6 kinase protein (PS6K) overexpression in a series of 452 node-negative premenopausal early-stage breast cancer patients (median follow-up: 10.8 years). Immunohistochemistry was used to assess PS6K expression in the primary tumour, which had previously been analysed for a panel of established prognostic factors in breast cancer. In a univariate analysis, PS6K overexpression was associated with worse distant disease-free survival as well as impaired locoregional control (HR 1.80, P 0.025 and HR 2.50, P 0.006, respectively). In a multivariate analysis including other prognostic factors, PS6K overexpression remained an independent predictor for poor locoregional control (RR 2.67, P 0.003). To our knowledge, P70 S6 kinase protein is the first oncogenic marker that has prognostic impact on locoregional control and therefore may have clinical implications in determining the local treatment strategy in early-stage breast cancer patients

The impact of loco-regional recurrences on metastatic progression in early-stage breast cancer: a multistate model

To study whether the effects of prognostic factors associated with the occurrence of distant metastases (DM) at primary diagnosis change after the incidence of loco-regional recurrences (LRR) among women treated for invasive stage I or II breast cancer. The study population consisted of 3,601 women, enrolled in EORTC trials 10801, 10854, or 10902 treated for early-stage breast cancer. Data were analysed in a multivariate, multistate model by using multivariate Cox regression models, including a state-dependent covariate. The presence of a LRR in itself is a significant prognostic risk factor (HR: 3.64; 95%-CI: 2.02-6.5) for the occurrence of DM. Main prognostic risk factors for a DM are young age at diagnosis (</=40: HR: 1.79; 95%-CI: 1.28-2.51), larger tumour size (HR: 1.58; 95%-CI: 1.35-1.84) and node positivity (HR: 2.00; 95%-CI: 1.74-2.30). Adjuvant chemotherapy is protective for a DM (HR: 0.66; 95%-CI: 0.55-0.80). After the occurrence of a LRR the latter protective effect has disappeared (P = 0.009). The presence of LRR in itself is a significant risk factor for DM. For patients who are at risk of developing LRR, effective local control should be the main target of therapy

Cтруктурні, оптичні і термоелектричні властивості плівок та наночастинок ZnO, CZTS, CZTSe для фото- і термоперетворювачів

Дисертаційна робота присвячена оптимізації основних фотоелектричних характеристик, а саме квантового виходу (Q), густини струму короткого замикання (Jsc), ефективності (η) плівкових ФЕП на основі ГП n-CdS(ZnSe, ZnS)/p-(CZTS, CdTe) із струмознімальними контактами n-ITO(ZnO); дослідженню морфологічних особливостей, структурних, субструктурних, оптичних, термоелектричних властивостей та елементного складу плівок ZnO, CZTS, нанесених методом пульсуючого спрей піролізу, для використання у ФЕП та наноструктурованого матеріалу на основі НЧ CZTSe, синтезованих колоїдним методом, для застосування у ТЕП, що можуть працювати паралельно з ФЕП. Встановлені взаємозв’язки між фізико- та хіміко-технологічними умовами нанесення плівок та синтезу НЧ, наноструктурованого матеріалу на їх основі, та структурними, субструктурними, оптичними, термоелектричними властивостями, елементним складом будуть використані для подальшого створення ФЕП та ТЕП з покращеними характеристиками.Диссертационная работа посвящена оптимизации основных фотоэлектрических характеристик, а именно квантового выхода (Q), плотности тока короткого замыкания (Jsc), эфективности (η) плёночных ФЭП на основе ГП n-CdS(ZnSe, ZnS)/p-(CZTS, CdTe) с токособирающими контактами ITO(ZnO); исследованию морфологических особенностей, структурных, субструктурных, оптических, термоэлектрических свойств и элементного состава плёнок ZnO, CZTS, нанесённых методом пульсирующего спрей-пиролиза, для применения у вышеуказанных ФЭП и наноструктурированного материала на основе НЧ CZTSe, синтезированных колоидальным методом, для использования у ТЭП, которые могут работать паралельно с ФЭП. Установленные взаимосвязи между физико- и химико-технологическими условиями нанесения плёнок, синтеза НЧ, наноструктурированного материала на их основе, и структурными, субструктурными, оптическими, термоэлектрическими свойствами, элементным составом будут использованы для создания ФЭП и ТЭП с улучшенными характеристиками.PhD thesis is devoted both to the optimization of basic photoelectric characteristics (quantum yield (Q), density of short circuit current (Jsc), efficiency (η)) of solar cells based on n-CdS(ZnSe, ZnS)/p-(CZTS, CdTe) heterojunctions with n-ITO(ZnO) frontal contacts, and to the investigation of morphological, structural, substructural, optical, thermoelectric properties and chemical composition of: (I) ZnO, CZTS films deposited by spray pyrolysis for application in solar cells; (II) nanostructured materials based on CZTSe nanocrystals synthesized by colloidal method for application in thermoelectric devices which can work simultaneously with solar cells. In the work, modeling approbation was performed by means of investigating the effect of optical and recombination losses on Q, Jsc, η of solar cells based on n-CdS(ZnS)/p-CdTe heterojunctions. Afterwards, the investigation of these losses on the photoelectric characteristics of solar cells based on n-CdS(ZnSe, ZnS)/p-CZTS heterojunctions with n-ITO(ZnO) frontal contacts was carried out with the help of the approbated procedure. Taking into account the results of mathematical modeling, the solar cells based on ZnO frontal contact and CZTS absorber layer were considered. For this purpose, the automated setup for the deposition of ZnO and CZTS films by pulsed spray pyrolysis technique was developed. The in-depth investigation of influence of the main growth conditions of layers’ deposition (substrate temperature (Ts), volume of initial precursor (Vs)) on structural (grains size, phase composition, texture quality, lattice parameters), substructural (coherent scattering domain sizes, level of microdeformations and microstresses, density of dislocations at the boundaries and in the volume of subgrains), optical (transmission coefficients, absorbance, band gap) properties and chemical composition of ZnO, CZTS films, as well as the determination of optimal conditions to obtain the specified films were carried out. Since the solar cells operate at the elevated temperatures, it was proposed to use the additional thermal energy by means of its conversion into electrical energy by use of the thermoelectric devices. For this purpose, the nanostructured thermoelectric material based on CZTSe nanocrystals synthesized by the colloidal method was obtained. The influence of kinetic conditions, namely type of phosphonic acid, on morphological (size, shape), structural (phase composition), optical (absorbance, band gap) properties and chemical composition of CZTSe nanocrystals was determined. The influence of chemical composition on the main thermoelectric properties (concentration (p) and mobility ( u ) of majority charge carriers, relative electrical conductivity ( k ), Seebeck coefficient (SZ)) of nanostructured material based on CZTSe nanocrystals was investigated. The established correlations between the film, nanocrystals growth conditions and structural, substructural, optical, thermoelectric properties, chemical composition will be applied for further development of solar cells and thermoelectric devices with the enhanced characteristics

Author correction : a global database for metacommunity ecology, integrating species, traits, environment and space

Correction to: Scientific Data https://doi.org/10.1038/s41597-019-0344-7, published online 08 January 202