ChiroVox: a public library of bat calls.

Recordings of bat echolocation and social calls are used for many research purposes from ecological studies to taxonomy. Effective use of these relies on identification of species from the recordings, but comparative recordings or detailed call descriptions to support identification are often lacking for areas with high biodiversity. The ChiroVox website (https://www.chirovox.org) was created to facilitate the sharing of bat sound recordings together with their metadata, including biodiversity data and recording circumstances. To date, more than 30 researchers have contributed over 3,900 recordings of nearly 200 species, making ChiroVox the largest open-access bat call library currently available. Each recording has a unique identifier that can be cited in publications; hence the acoustic analyses are repeatable. Most of the recordings available through the website are from bats whose species identities are confirmed, so they can be used to determine species in recordings where the bats were not captured or could not be identified. We hope that with the help of the bat researcher community, the website will grow rapidly and will serve as a solid source for bat acoustic research and monitoring.

A portable magneto-optical trap with prospects for atom interferometry in civil engineering.

The high precision and scalable technology offered by atom interferometry has the opportunity to profoundly affect gravity surveys, enabling the detection of features of either smaller size or greater depth. While such systems are already starting to enter into the commercial market, significant reductions are required in order to reach the size, weight and power of conventional devices. In this article, the potential for atom interferometry based gravimetry is assessed, suggesting that the key opportunity resides within the development of gravity gradiometry sensors to enable drastic improvements in measurement time. To push forward in realizing more compact systems, techniques have been pursued to realize a highly portable magneto-optical trap system, which represents the core package of an atom interferometry system. This can create clouds of 107 atoms within a system package of 20 l and 10 kg, consuming 80 W of power.This article is part of the themed issue 'Quantum technology for the 21st century'.

Harnessing ester bond chemistry for protein ligation.

The hydrolysis potential of ester bonds in covalently cross-linking proteins is captured in our novel protein ligation technology. This new type of "molecular superglue" based on the spontaneously-formed Thr-Gln ester bonds found in cell-surface adhesins, affords a unique mechanism to both rationally assemble and disassemble complex protein nanomaterials.

Total Chemical Synthesis of an Orf Virus Protein, ORFV002, an Inhibitor of the Master Gene Regulator NF-κB.

ORFV002 is a novel orf viral protein (117 Aa) that inhibits nuclear events through the regulation of the transcriptional activity of NF-κB, a master regulator of human gene expression (Diel et al., J Virol 2011, 85, 264-275). It is identified as the first nuclear inhibitor of NF-κB produced by orf virus (ORFV) and no homologues in other genera of the Chordopoxvirinae subfamily have been reported to date (Diel et al., J Virol 2011, 85, 264-275). Our molecular structure predictions suggest that ORFV002 may mimic part of IκB, an inhibitor and natural human partner of NF-κB. Recent advances in total chemical synthesis of proteins have provided solutions in overcoming challenges of current recombinant methods of protein isolation for structure elucidation. Aided by Boc solid phase peptide synthesis and native chemical ligation, ORFV002 was successfully synthesized in multimilligram amounts in good yield and high purity.

National audit of the sensitivity of double-contrast barium enema for colorectal carcinoma, using control charts For the Royal College of Radiologists Clinical Radiology Audit Sub-Committee.

AIM: To audit the sensitivity of double-contrast barium enema (DCBE) for colorectal carcinoma, as currently practised in UK departments of radiology. METHODS: As part of its programme of national audits, the Royal College of Radiologists Clinical Radiology Audit Sub-Committee undertook a retrospective audit of the sensitivity of DCBE for colorectal carcinoma during 2002. The following targets were set: demonstration of a lesion > or =95%; correct identification as a carcinoma > or =90%. RESULTS: Across the UK, 131 departments took part in the audit, involving 5454 examinations. The mean demonstration rate was 92.9% and the diagnosis rate was 85.9%, slightly below the targets set. The equivocal rate (lesion demonstrated, but not defined as malignant) was 6.9%, the perception failure rate was 2.8% and the technical failure rate was 4.4%. Control-chart methodology was used to analyze the data and to identify any departments whose performance was consistent with special-cause variation. CONCLUSION: When compared with the diagnosis rate (84.6%) and demonstration rate (92.7%) reported in the Wessex Audit 1995, [Thomas RD, Fairhurst JJ, Frost RA. Wessex regional audit: barium enema in colo-rectal carcinoma. Clin Radiol 1995;50:647-50.] a similar level of performance was observed in the NHS today, implying that the basic process for undertaking and reporting DCBE has remained relatively unchanged over the last few years. Improvement in the future will require fundamental changes to the process of reporting DCBE, in order to minimize the perception failure rate and accurately to describe lesions, so reducing the equivocal rate. Control-chart methodology has a useful role in identifying strategies to deliver continual improvement.

Re-audit of radiotherapy waiting times 2003.

AIMS: There has been increasing concern, by clinical oncologists in the UK, about the continuing long waiting times for radiotherapy treatment. An audit of patients starting treatment in 1 week in 2003 was carried out to determine waiting times and to compare current results with those obtained from a similar audit in 1998. MATERIALS AND METHODS: All centres in the UK completed the audit, which recorded waiting-list status and treatment intent for all new treatments started in 1 week, date of booking form completion and fractionation scheme used. RESULTS: Waiting times have lengthened in most centres for all categories of patients although, for palliative treatments, there was no additional increase in median waiting time compared with the last audit. Fewer patients in all categories are being treated within the Joint Collegiate Council for Oncology (JCCO) guidelines. Single-fraction treatments are now common for palliation. Most adjuvant treatment uses one of three prescriptions. In each Strategic Health Authority (StHA), the same proportion of the total number of patients with cancer seemed to be given radiotherapy. There was no obvious simple correlation of radiographer, physicist or treatment machine numbers with waiting times. CONCLUSION: The results of this survey suggest a continuing mismatch between capacity and demand. Increased complexity of radical treatments, and possibly more patients being referred for treatment, may have been offset in part by reduced fractionation for palliation.

A national audit of radiotherapy in head and neck cancer.

AIMS: To undertake a national audit of radiotherapy practice in head and neck cancer to estimate compliance with published guidelines and national standards. METHODS: A two-part electronic data entry form was distributed to all U.K. radiotherapy centres in September 2000. The first part examined the centres' policies for managing interruptions, the second collected summaries of the management of 50 consecutive patients treated in each centre for head and neck cancer. The outcome measures were: frequency and causes of interruptions to therapy: policy and compliance with policy for managing interruptions; prolongation; and time between first visit to clinic and start of treatment. RESULTS: Fifty-five out of 56 centres returned data on a total of 2553 patients. Overall, 1467 (55%) patients had one or more treatment interruptions. Of patients whose treatment was interrupted, 56% still completed on time due to compensatory steps, but in 32% no attempted compensation was undertaken. Seven centres had no policy for dealing with treatment interruptions. Centres whose policies included treatment on bank (public) holidays achieved higher compliance and fewer prolonged cases than those whose policies did not. Average time from first visit to head and neck oncology clinic to starting radiotherapy was 40 days; six centres had an average wait of less than 28 days. CONCLUSIONS: This audit demonstrates wide variations in the quality of care between centres, failure to comply with guidelines for compensation for gaps and failure to meet national targets (for waiting times) that have serious implications both for patient outcomes and for the success of the National Cancer Plan.

Provision of acupuncture in a university health centre--a clinical audit.

A retrospective audit was carried out between May 1999 and April 2000 at a university-based acupuncture clinic. Two acupuncturists saw a total of 69 clients of whom three-quarters were female; just over a third were less than 29 years of age; two-thirds were below the age of 40; 67% of clients were Caucasians; a third smoked; three-quarters currently consumed some alcohol. Most had no experience of using complementary and alternative medicine (CAM), therefore the service provided the first access to CAM. Of those attending a follow-up appointment, 43 (80%) reported feeling better, 10 the same and one worse. No side-effects were reported by 50 (73%) clients, but four reported minor side-effects (one bruising and three drowsiness). The process of carrying out the audit provided the opportunity for the practitioners to reflect on their clinical practice and improve service delivery.

Pitfalls in the use of thyrotropin concentration as a first-line thyroid-function test.

Measurement of thyrotropin concentration alone as a first-line thyroid-function test fails to indicate hypopituitarism in a number of patients. Using a combination of thyrotropin and thyroxine assays, we analysed 56,000 tests for a population of 471,000 over 12 months. 15 patients with clinically unsuspected hypopituitarism were detected, indicating that the occurrence of hypopituitarism might be underestimated.

Randomised trial of iodine intake and thyroid status in preterm infants.

BACKGROUND: Low levels of circulating thyroid hormones have been associated with poorer general and neurodevelopmental outcome in preterm babies and it has been speculated that the association is causal. Low levels of circulating thyroid hormone have been reported after inadequate intake of iodine in preterm infants being fed milk formula. AIM: To investigate whether increased iodine intake from supplemented preterm formula would improve thyroid hormone levels in preterm babies (this study) and hence improve neurodevelopmental status (planned subsequent study). METHOD: A total of 121 preterm infants were entered into a randomised controlled trial of standard (68 microg/l) versus increased (272 microg/l) iodine in preterm formula. RESULTS: The two groups were comparable at recruitment. No evidence of an effect of the intervention on thyroid hormone levels was seen up to 41 weeks after conception. CONCLUSION: Calls for increased iodine content of preterm infant formulas are not justified by this study.

Structures of m-iodo Hoechst-DNA complexes in crystals with reduced solvent content: implications for minor groove binder drug design.

The DNA photosensitisers m-iodo Hoechst and m-iodo, p-methoxy Hoechst have been co-crystallised with the oligonucleotide d(CGCGAATTCGCG)(2)and their crystal structures determined. The crystals were then subjected to slow dehydration, which reduced their solvent contents from 40 (normal) to 30 (partially dehydrated) and then 20% (fully dehydrated) and caused a reduction in cell volume from 68,000 to 60,000 then 51,000 A(3). The dehydration resulted in a dramatic enhancement of diffraction resolution from approximately 2.6 to beyond 1.5 A. Crystal structures have also been determined for the partially and fully dehydrated states. The fully dehydrated crystals consist of an infinite polymeric network, in which neighbouring dodecamer duplexes are crosslinked through phosphate oxygens via direct bonding to bridging magnesium cations. This unique three-dimensional structure for DNA is described in detail in the following companion paper. The present paper details evidence from the sequence of crystal structures that the DNA is able to breathe locally, allowing the ligand to leave the minor groove, re-orient in the surrounding solvent medium and then re-enter the groove in a different orientation and location. The rearrangement of the minor groove binding ligands during the dehydration process mimics the binding behaviour of these ligands in solution and in vivo. We also present details of the DNA-ligand interactions that are consistent with a hydrogen atom ion mechanism for photocleavage of DNA.

Intermolecular interactions and water structure in a condensed phase B-DNA crystal.

By controlled dehydration, the unit cells of dodecamer DNA-drug crystals have been shrunk from 68,000 (normal state) to 60,000 (partially dehydrated intermediate state) to 51,000 A(3) (fully dehydrated state), beyond which no further solvent loss occurs. The total solvent content in the normal crystals is approximately 40% by volume, reducing to approximately 20% in the fully dehydrated phase. The 25% reduction in cell volume induced a dramatic enhancement in the resolution of the X-ray diffraction data (from 2. 6 to beyond 1.5 A). We have determined the structures of the normal, partially dehydrated and fully dehydrated crystals. Details of the ligand binding have been presented in the preceding article. The present paper describes the unique features of the structure of the fully dehydrated phase. This structure was refined with 9,015 unique observed reflections to R = 14.9%, making it one of the most reliable models of B -form DNA available. The crystals exist as infinite polymeric networks, in which neighbouring dodecamer duplexes are crosslinked through phosphate oxygens via direct bonding to magnesium cations. The DNA is packed so tightly that there is essentially only a single layer of solvent between adjacent molecules. The details of the crystal packing, magnesium bridging, DNA hydration and DNA conformation are described and compared with other experimental evidence related to DNA condensation.

2-ethylthio-9-methyl-1,4-dihydroacridine-1,4-dione and 9-methyl-2-(4-tolylthio)-1,4-dihydroacridine-1,4-dione.

The title compounds, C16H13NO2S, (I), and C21H15NO2S, (II), have similar molecular structures that differ only in the side groups attached to the S atom. The crystal packing is dominated by pi-pi stacking interactions, involving acridinedione-acridinedione overlap in (I) and both acridinedione-acridinedione and acridinedione-tolyl overlap in (II).

Minor groove binding of a bis-quaternary ammonium compound: the crystal structure of SN 7167 bound to d(CGCGAATTCGCG)2.

The X-ray crystal structure of the complex between the synthetic antitumour and antiviral DNA binding ligand SN 7167 and the DNA oligonucleotide d(CGCGAATTCGCG)2 has been determined to an R factor of 18.3% at 2.6 A resolution. The ligand is located within the minor groove and covers almost 6 bp with the 1-methylpyridinium ring extending as far as the C9-G16 base pair and the 1-methylquinolinium ring lying between the G4-C21 and A5-T20 base pairs. The ligand interacts only weakly with the DNA, as evidenced by long range contacts and shallow penetration into the groove. This structure is compared with that of the complex between the parent compound SN 6999 and the alkylated DNA sequence d(CGC[e6G]AATTCGCG)2. There are significant differences between the two structures in the extent of DNA bending, ligand conformation and groove binding.

Interpretive group psychotherapy and dependent day hospital patients: a preliminary investigation.

A small group of highly dependent day hospital patients, together with a small number of 'potential' day hospital referrals sharing similar characteristics, were treated in twice weekly interpretive group psychotherapy for between seven and nine months. At the end of treatment three of four day hospital patients had made a successful separation from the day hospital, and at nine month follow-up outcome appeared improved. Only two of the six non-day hospital patients remained in the group, the reasons for which are discussed. The method of evaluation proved manageable, although it would be more appropriate to studies involving larger numbers and possibly control interventions. It is suggested that the role of interpretive group psychotherapy in rehabilitation deserves further investigation.

Orthodontics, prosthodontics, and periodontics: a multidisciplinary approach.

Congenitally missing lateral incisors are not a rarity in any dental practice, yet the treatment for this condition is usually a challenge. Various treatment possibilities and their indications, contraindications, and problems are discussed. A case report involving orthodontic treatment followed by placement of implants and single-tooth porcelain-fused-to-metal crowns.

Designer DNA-binding drugs: the crystal structure of a meta-hydroxy analogue of Hoechst 33258 bound to d(CGCGAATTCGCG)2.

An analogue of the DNA binding compound Hoechst 33258, which has the para hydroxyl group altered to be at the meta position, together with the replacement of one benzimidazole group by pyridylimidazole, has been cocrystallized with the dodecanucleotide sequence d(CGCGAATTCGCG)2. The X-ray structure has been determined at 2.2 A resolution and refined to an R factor of 20.1%. The ligand binds in the minor groove at the sequence 5'-AATTC with the bulky piperazine group extending over the CxG base pair. This binding is stabilised by hydrogen bonding and numerous close van der Waals contacts to the surface of the groove walls. The meta-hydroxyl group was found in two distinct orientations, neither of which participates in direct hydrogen bonds to the exocyclic amino group of a guanine base. The conformation of the drug differs from that found previously in other X-ray structures of Hoechst 33258-DNA complexes. There is significant variation between the minor groove widths in the complexes of Hoechst 33258 and the meta-hydroxyl derivative as a result of these conformational differences. Reasons are discussed for the inability of this derivative to actively recognise guanine.

Thyroid stimulating hormone measurement using a third generation immunometric assay.

After an initial evaluation of the standard procedure for performance of a third generation TSH (thyroid stimulating hormone) assay (Amerlite TSH-30) modifications were made to standardize the timing of measurement of light emission following signal reagent addition. By adopting this optimized procedure, a significant improvement in assay sensitivity was achieved when compared to a second generation TSH assay (DAKO). Using the optimized assay the sensitivity was 0.003 mU/L (20 replicates of zero) or 0.009 mU/L [22% CV (coefficient of variation) from the precision profile]. Recovery of added TSH and parallelism of the assay were good. A significant negative bias was detected for the Amerlite TSH-30 assay when compared to the DAKO assay (log y = 0.92 log x-0.33, n = 210). Excellent discrimination was achieved between euthyroid, hypothyroid and thyrotoxic subjects. A high percentage of thyrotoxic patients had undetectable TSH and the spread of values between thyrotoxic and euthyroid was greater with the third generation assay. In patients receiving thyroxine therapy a higher percentage had detectable TSH values. The optimized Amerlite TSH 30 assay offers improved assay performance when compared to a second generation assay.

Non-surgical management of early breast cancer in the United Kingdom: work-load, referral patterns and staging. Clinical Audit Sub-committee of the Faculty of Clinical Oncology, Royal College of Radiologists, and the Joint Council for Clinical Oncology.

This is the first of five papers describing the results of a national survey of the non-surgical treatment of early breast cancer in the UK. The topics include: work-load, referral patterns, participation in specialist clinics, use of treatment policies, availability of outcome data, quality of pathology reports, and staging investigations.