A phase II study of vorinostat (MK-0683) in patients with polycythaemia vera and essential thrombocythaemia

Inhibition of histone deacetylases may be an important target in patients with myeloproliferative neoplasms. This investigator-initiated, non-randomized, open-label phase II multi-centre study included 63 patients (19 essential thrombocythaemia, 44 polycythaemia vera) from 15 centres. The primary objective was to evaluate if vorinostat was followed by a decline in clonal myeloproliferation as defined by European Leukaemia Net. Thirty patients (48%) completed the intervention period (24 weeks of therapy). An intention-to-treat response rate of 35% was identified. Pruritus was resolved [19% to 0% (P = 0·06)] and the prevalence of splenomegaly was lowered from 50% to 27% (P = 0·03). Sixty-five per cent of the patients experienced a decrease in JAK2 V617F allele burden (P = 0·006). Thirty-three patients (52% of patients) discontinued study drug before end of intervention due to adverse events (28 patients) or lack of response (5 patients). In conclusion, vorinostat showed effectiveness by normalizing elevated leucocyte and platelet counts, resolving pruritus and significantly reducing splenomegaly. However, vorinostat was associated with significant side effects resulting in a high discontinuation rate. A lower dose of vorinostat in combination with conventional and/or novel targeted therapies may be warranted in future studies.

Marine or estuarine radiocarbon reservoir corrections for mollusks? A case study from a medieval site in the south of England

Mollusk shells are frequently radiocarbon dated and provide reliable calibrated age ranges when the regional marine reservoir correction is well-established. For mollusks from an estuarine environment the reservoir correction may be significantly different than the regional marine reservoir correction due to the input of bedrock or soil derived carbonates. Some mollusk species such as oysters are tolerant of a significant range of salinities which makes it difficult to determine which reservoir correction is appropriate. A case study is presented of an anomalous radiocarbon age for an oyster shell paint dish found in the fabric of the ruined nave walls of St Mary's Church, Shoreham-by-Sea, West Sussex, England. Stable isotopes (delta O-18 and delta C-13) were used to establish the type of environment in which the oyster had lived. Paired marine and terrestrial samples from a nearby medieval site were radiocarbon dated to provide an appropriate reservoir correction.

Randomized Phase II trial of nintedanib, afatinib and sequential combination in castration-resistant prostate cancer

AIMS: The aim of this article was to evaluate afatinib (BIBW 2992), an ErbB family blocker, and nintedanib (BIBF 1120), a triple angiokinase inhibitor, in castration-resistant prostate cancer patients.

PATIENTS & METHODS: Patients were randomized to receive nintedanib (250 mg twice daily), afatinib (40 mg once daily [q.d.]), or alternating sequential 7-day nintedanib (250 mg twice daily) and afatinib (70 mg q.d. [Combi70]), which was reduced to 40 mg q.d. (Combi40) due to adverse events. The primary end point was progression-free rate at 12 weeks.

RESULTS: Of the 85 patients treated 46, 20, 16 and three received nintedanib, afatinib, Combi40 and Combi70, respectively. At 12 weeks, the progression-free rate was 26% (seven out of 27 patients) for nintedanib, and 0% for afatinib and Combi40 groups. Two patients had a ≥50% decline in PSA (nintedanib and the Combi40 groups). The most common drug-related adverse events were diarrhea, nausea, vomiting and lethargy.

CONCLUSION: Nintedanib and/or afatinib demonstrated limited anti-tumor activity in unselected advanced castration-resistant prostate cancer patients.

Access to the countryside of England and Wales: public/private partnership or the privatisation of public rights?

This paper examines the evolution of public rights of access to private land in England and Wales. Since the Eighteenth Century the administration and protection of these rights has been though a form of public/private partnership in which the judiciary, while maintaining the dominance of private property, have safeguarded de facto public access by refusing consistently to punish simple trespass. While this situation has been modified, principally by post-World War II legislation, to allow for some formalisation of access arrangements and consequent compensation to landowners in areas of high recreational pressure and low legal accessibility, recent policy initiatives suggest that the balance of the partnership has now shifted in favour of landowners. In particular, the new access payment schemes, developed by the UK Government in response to the European Commission's Agri-Environment Regulations, locate the landowner as the beneficiary of the partnership, financed by tax revenue and justified on the spurious basis of improved 'access provision'. As such the state, as the former upholder of citizen rights, now assumes the duplicitous position of underwriting private property ownership through the commodification of access, while proclaiming a significant improvement in citizens' access rights.

A genealogy of the kings of England in papal Avignon: British Library, Egerton MS. 1500

This is one of three articles in eBLJ (2013) dedicated to the "Abreujamen de las estorias", British Library Egerton MS 1500. The other two articles are: Federico Botana,' The Making of "L'Abreujamen de las estorias": British Library Egerton MS 1500', eblj (2013), article 16. Alexander Ibarz, 'The Provenance of the "Abreujamens de las estorias" (London, British Library, Egerton MS. 1500) and the Identification of Scribal Hands (c. 1323)' eblj (2013), article 17. Leglu's article, eblj (2013), article 18, examines the various political agendas that emerge in the depiction of the kings of Britain and England, from Brutus to Edward II.

Biochemical evolution II: Origin of life in tubular microstructures on weathered feldspar surfaces

Mineral surfaces were important during the emergence of life on Earth because the assembly of the necessary complex biomolecules by random collisions in dilute aqueous solutions is implausible. Most silicate mineral surfaces are hydrophilic and organophobic and unsuitable for catalytic reactions, but some silica-rich surfaces of partly dealuminated feldspars and zeolites are organophilic and potentially catalytic. Weathered alkali feldspar crystals from granitic rocks at Shap, north west England, contain abundant tubular etch pits, typically 0.4–0.6 μm wide, forming an orthogonal honeycomb network in a surface zone 50 μm thick, with 2–3 × 106 intersections per mm2 of crystal surface. Surviving metamorphic rocks demonstrate that granites and acidic surface water were present on the Earth’s surface by ∼3.8 Ga. By analogy with Shap granite, honeycombed feldspar has considerable potential as a natural catalytic surface for the start of biochemical evolution. Biomolecules should have become available by catalysis of amino acids, etc. The honeycomb would have provided access to various mineral inclusions in the feldspar, particularly apatite and oxides, which contain phosphorus and transition metals necessary for energetic life. The organized environment would have protected complex molecules from dispersion into dilute solutions, from hydrolysis, and from UV radiation. Sub-micrometer tubes in the honeycomb might have acted as rudimentary cell walls for proto-organisms, which ultimately evolved a lipid lid giving further shelter from the hostile outside environment. A lid would finally have become a complete cell wall permitting detachment and flotation in primordial “soup.” Etch features on weathered alkali feldspar from Shap match the shape of overlying soil bacteria.

Folk-songs of England,

Pl. no.: 12593, 13678, 12993, 13587, 13652.

Memoirs of Elizabeth Stuart, queen of Bohemia, daughter of King James the First. Including sketches of the state of society in Holland and Germany, in the 17th century.

Mode of access: Internet.

Omitted chapters of the history of England from the death of Charles I. to the battle of Dunbar.

Vol. II. has title: History of the commonwealth of England from the death of Charles I to the expulsion of the Long Parliament by Cromwell: being omitted chapters of the history of England.

The history of England: from the earliest period to the death of Elizabeth.

Each v. has also special t.-p.

The life of Queen Elizabeth,

Mode of access: Internet.

Marie Stuart, queen of Scots (a concise bibliography)

"Edition limited to 250 copies."

The traditional games of England, Scotland, and Ireland, with tunes, singing-rhymes, and methods of playing according to the variants extant and recorded in different parts of the Kingdom;

"List of authorities": v. 1, p. xi-xiv; v. 2, p. vii-ix.

Chief contemporary dramatists; twenty plays from the recent drama of England, Ireland, America, Germany, France, Belgium, Norway, Sweden, and Russia,

--Appendix; Authors and plays. Notes on the production of plays. A reading list in contemporary dramatists. A working book list in contemporary drama. Index to charaters.