Left Bundle Branch Block, an Old–New Entity

Left bundle branch block (LBBB) is generally associated with a poorer prognosis in comparison to normal intraventricular conduction, but also in comparison to right bundle branch block which is generally considered to be benign in the absence of an underlying cardiac disorder like congenital heart disease. LBBB may be the first manifestation of a more diffuse myocardial disease. The typical surface ECG feature of LBBB is a prolongation of QRS above 0.11 s in combination with a delay of the intrinsic deflection in leads V5 and V6 of more than 60 ms and no septal q waves in leads I, V5, and V6 due to the abnormal septal activation from right to left. LBBB may induce abnormalities in left ventricular performance due to abnormal asynchronous contraction patterns which can be compensated by biventricular pacing (resynchronization therapy). Asynchronous electrical activation of the ventricles causes regional differences in workload which may lead to asymmetric hypertrophy and left ventricular dilatation, especially due to increased wall mass in late-activated regions, which may aggravate preexisting left ventricular pumping performance or even induce it. Of special interest are patients with LBBB and normal left ventricular dimensions and normal ejection fraction at rest but who may present with an abnormal increase in pulmonary artery pressure during exercise, production of lactate during high-rate pacing, signs of ischemia on myocardial scintigrams (but no coronary artery narrowing), and abnormal ultrastructural findings on myocardial biopsy. For this entity, the term latent cardiomyopathy had been suggested previously

Atypical ductal hyperplasia is a multipotent precursor of breast carcinoma

The current model for breast cancer progression proposes independent “low‐grade (LG) like” and “high‐grade (HG) like” pathways but lacks a known precursor to HG cancer. We applied low coverage whole genome sequencing to atypical ductal hyperplasia (ADH) with and without carcinoma to shed light on breast cancer progression. 14/20 isolated ADH cases harboured at least one copy number alteration (CNA), but had fewer aberrations than LG or HG ductal carcinoma in situ (DCIS). ADH carried more HG‐like CNA than LG DCIS (eg. 8q gain). Correspondingly, 64% (7/11) of ADH cases with synchronous HG carcinoma were clonally related, similar to LG carcinoma (67%, 6/9). This study represents a significant shift in our understanding of breast cancer progression, with ADH as a common precursor lesion to the independent “low‐grade like” and “high‐grade like” pathways. These data suggest that ADH can be a precursor of HG breast cancer and that LG and HG carcinomas can evolve from a similar ancestor lesion. We propose that although LG DCIS may be committed to a LG molecular pathway, ADH may remain multipotent, progressing to either LG or HG carcinoma. This multipotent nature suggests that some ADH could be more clinically significant than LG DCIS, requiring biomarkers for personalising management

Molecular understanding of sulphuric acid-amine particle nucleation in the atmosphere

4 pages 359-363 in the print version, additional 7 pages online.Peer reviewe

Eclipse Prediction on the Ancient Greek Astronomical Calculating Machine Known as the Antikythera Mechanism

The ancient Greek astronomical calculating machine, known as the Antikythera Mechanism, predicted eclipses, based on the 223-lunar month Saros cycle. Eclipses are indicated on a four-turn spiral Saros Dial by glyphs, which describe type and time of eclipse and include alphabetical index letters, referring to solar eclipse inscriptions. These include Index Letter Groups, describing shared eclipse characteristics. The grouping and ordering of the index letters, the organization of the inscriptions and the eclipse times have previously been unsolved. A new reading and interpretation of data from the back plate of the Antikythera Mechanism, including the glyphs, the index letters and the eclipse inscriptions, has resulted in substantial changes to previously published work. Based on these new readings, two arithmetical models are presented here that explain the complete eclipse prediction scheme. The first model solves the glyph distribution, the grouping and anomalous ordering of the index letters and the structure of the inscriptions. It also implies the existence of lost lunar eclipse inscriptions. The second model closely matches the glyph times and explains the four-turn spiral of the Saros Dial. Together, these models imply a surprisingly early epoch for the Antikythera Mechanism. The ancient Greeks built a machine that can predict, for many years ahead, not only eclipses but also a remarkable array of their characteristics, such as directions of obscuration, magnitude, colour, angular diameter of the Moon, relationship with the Moon's node and eclipse time. It was not entirely accurate, but it was an astonishing achievement for its era