Core Imaging Library - Part I: a versatile Python framework for tomographic imaging.

We present the Core Imaging Library (CIL), an open-source Python framework for tomographic imaging with particular emphasis on reconstruction of challenging datasets. Conventional filtered back-projection reconstruction tends to be insufficient for highly noisy, incomplete, non-standard or multi-channel data arising for example in dynamic, spectral and in situ tomography. CIL provides an extensive modular optimization framework for prototyping reconstruction methods including sparsity and total variation regularization, as well as tools for loading, preprocessing and visualizing tomographic data. The capabilities of CIL are demonstrated on a synchrotron example dataset and three challenging cases spanning golden-ratio neutron tomography, cone-beam X-ray laminography and positron emission tomography. This article is part of the theme issue 'Synergistic tomographic image reconstruction: part 2'.

Early complications and implant loss in implant-based breast reconstruction with and without acellular dermal matrix (Tecnoss Protexa®): a comparative study.

INTRODUCTION: Acellular dermal matrix (ADM) may improve outcomes in implant-based breast reconstruction, but recent evidence suggests complication rates may be higher when ADM is used. We retrospectively compared early complications and implant loss in implant-based breast reconstruction (BR) with and without ADM to evaluate the safety of the procedure in our centre. METHODS: Case-notes of consecutive women undergoing implant-based BR from May 2011 to November 2012 were retrospectively reviewed. Data were extracted using a standardised pro-forma and the rate of early complications, major complications and implant loss compared between procedure groups. RESULTS: Forty-six implant-based reconstructions were performed for malignancy (n = 31, 67.4%) or prophylaxis (n = 15, 32.6%) in 31 women over the 18-month study period. ADM (Tecnoss Protexa(®), Tecnoss S.r.l.) was used in 31 (67.4%) cases. There were no differences in patient age, BMI, co-morbidities, smoking or chemotherapy between groups, but patients receiving ADM were more likely to have received radiotherapy prior to their reconstruction (n = 6, 30% vs. n = 0, 0%, p = 0.043). The overall rate of early complications was 26.1% (n = 12) but there was no significant difference between procedure groups (standard-n = 4, 27.7% vs. ADM-n = 8, 25.8%; p = 0.950). There were 2 (4.3%) major complications none of which were associated with ADM use (standard-n = 2, 13.3% vs. ADM-n = 0, 0.0%; p = 0.038). There were 6 (13.0%) implant losses of which 4 were in the ADM group (standard-n = 2, 13.3% vs. ADM-n = 4, 12.9%; p = 0.968). All of these were associated with pre-reconstruction radiotherapy. CONCLUSIONS: ADM-assisted implant-based reconstruction with Tecnoss Protexa(®) is safe and may improve outcomes for women by facilitating a single-stage procedure. Robust prospective evaluation is now needed to definitively evaluate the role of ADM in implant-based BR.

Incorporating clinical metadata with digital image features for automated identification of cutaneous melanoma.

BACKGROUND: Computer-assisted diagnosis (CAD) of malignant melanoma (MM) has been advocated to help clinicians to achieve a more objective and reliable assessment. However, conventional CAD systems examine only the features extracted from digital photographs of lesions. Failure to incorporate patients' personal information constrains the applicability in clinical settings. OBJECTIVES: To develop a new CAD system to improve the performance of automatic diagnosis of melanoma, which, for the first time, incorporates digital features of lesions with important patient metadata into a learning process. METHODS: Thirty-two features were extracted from digital photographs to characterize skin lesions. Patients' personal information, such as age, gender and, lesion site, and their combinations, was quantified as metadata. The integration of digital features and metadata was realized through an extended Laplacian eigenmap, a dimensionality-reduction method grouping lesions with similar digital features and metadata into the same classes. RESULTS: The diagnosis reached 82.1% sensitivity and 86.1% specificity when only multidimensional digital features were used, but improved to 95.2% sensitivity and 91.0% specificity after metadata were incorporated appropriately. The proposed system achieves a level of sensitivity comparable with experienced dermatologists aided by conventional dermoscopes. This demonstrates the potential of our method for assisting clinicians in diagnosing melanoma, and the benefit it could provide to patients and hospitals by greatly reducing unnecessary excisions of benign naevi. CONCLUSIONS: This paper proposes an enhanced CAD system incorporating clinical metadata into the learning process for automatic classification of melanoma. Results demonstrate that the additional metadata and the mechanism to incorporate them are useful for improving CAD of melanoma.

Immediate free tissue transfer for coverage of Achilles tendon injury or reconstruction.

BACKGROUND: The restoration of function and contour to the Achilles region is a complex problem. This is reflected in the variety of reconstructive options described in the literature. The aim however remains to normalise the range of movement at the ankle joint and restore the power of plantar flexion. Few techniques have demonstrated this. METHODS: Six patients underwent soft tissue reconstruction over the Achilles tendon with a free scapular flap. Two ruptured Achilles tendons were reconstructed with FHL transfers. RESULTS: All six flaps remained viable and achieved stable coverage over the Achilles tendon. Five of the six required thinning for use of normal foot wear. Those that had FHL transfer normalised their range of movement. CONCLUSIONS: It has previously been shown that FHL transfer provides optimum results in terms of functional outcome while here the scapular flap has fulfilled the requirement to restore the contour of this region.

Aplasia cutis congenita. A case of scalp defect repair using two opposing bipedicled local flaps.

Aplasia cutis congenita is a rare congenital condition characterised by the absence of some or all layers of the skin. It may also be associated with absence of underlying muscle and bone. Where dura is exposed there exists a risk of ulceration and haemorrhage and thus primary closure is indicated. We report a case of cutis aplasia successfully closed with opposing bipedicled flaps. To our knowledge this is a novel approach which offers a simple safe technique that can be applied in the neonate.

The detection of tyrosinase mRNA in peripheral blood samples is unlikely to aid in the management of patients with localised malignant melanoma.

A number of authors have reported the detection of tyrosinase mRNA in the peripheral blood of patients with malignant melanoma using the reverse transcription polymerase chain reaction (RT-PCR). The precise value of this assay as a prognostic tool, however, remains in doubt. This is particularly so with relation to localised disease, where relatively little data has been accumulated. In this study we analysed the peripheral blood of 50 consecutive patients with primary malignant melanoma referred to a plastic surgical centre with the facility of a pigmented lesion clinic. Samples were analysed from an additional 35 patients with advanced melanoma disease and 35 patients with benign pigmented cutaneous lesions. We were able to identify tyrosinase transcripts in the peripheral blood of only two of 50 patients with localised disease. Of those with more advanced disease, a positive finding was found in three with regional disease and four patients with metastatic spread. Stage of disease was found to correlate significantly with PCR status. No correlation was identified with other prognostic markers or with outcome over a three-year period. This data would support the conclusion that the detection of tyrosinase mRNA in peripheral blood is likely to be of little value as an aid in the management of patients with early malignant melanoma.

Detection of melanoma seeding during surgical procedures--an RT-PCR based model.

AIM: It has long been suggested that malignant cells may be shed into the blood stream during any given surgical procedure for cancer. A number of studies have now reported the detection of occult melanoma cells in peripheral blood using a reverse transcriptase polymerase chain reaction (RT-PCR) based assay. The principal aim of these studies has been to determine a prognostic value for the test and not to evaluate the influence of intervention upon results. METHODS: In this pilot study we aimed to determine whether the assay could be used as a model to detect cells that are seeded during surgery. Peripheral blood samples were obtained pre- and post-operatively on twenty patients undergoing surgery for malignant melanoma - ten with primary disease and ten undergoing regional lymphadenectomy. A further ten patients undergoing surgery for non-melanoma conditions provided controls. RESULTS: Using RT-PCR, it was possible to identify tyrosinase transcripts in the peripheral blood of one of ten patients undergoing excision of local disease and four of ten undergoing surgery for regional metastatic disease. CONCLUSION: It was concluded that this technique does enable detection of a greater percentage of RT-PCR findings post-operatively. This in turn may provide a means for optimizing or comparing surgical techniques and provides a potential guide in the use of adjuvant therapies.

The bisindolylmaleimide protein kinase C inhibitor, Ro 32-2241, reverses multidrug resistance in KB tumour cells.

Ro 32-2241 is a bisindolylmaleimide that selectively inhibits protein kinase C (PKC) as compared with other protein kinases. Experiments were carried out to examine its potential as a multidrug resistance-reversing agent. Ro 32-2241 inhibited efflux, and increased accumulation, of [3H]-daunomycin in multidrug-resistant (MDR) KB-8-5 and KB-8-5-11 cells and had no effect on drug-sensitive KB-3-1 cells. Ro 32-2241 completely reversed the doxorubicin resistance of KB-8-5 and KB-8-5-11 cells, showing no effect on the sensitivity of drug-sensitive KB-3-1 cells. The potency of Ro 32-2241 was comparable with that of cyclosporin A and better than that of verapamil, known modulators of multidrug resistance. Ro 32-2241 also completely reversed the taxol resistance of KB-8-5 cells and partially reversed the resistance of KB-8-5-11 cells. Vinblastine resistance was also partially reversed. Mechanistic experiments were carried out to determine whether Ro 32-2241 interacted with P-glycoprotein (Pgp) directly. Increased efflux of [14C]-Ro 32-2241 was seen with the more resistant KB-8-5-11 cells (although the percentage effluxed was very low as compared with [3H]-daunomycin), suggesting that Ro 32-2241 can act as a substrate for Pgp. Direct interaction of Ro 32-2241 with Pgp was confirmed by demonstration that it inhibited binding of [3H]-azidopine to Pgp in KB-8-5-11 membranes. In conclusion, Ro 32-2241, acting directly on Pgp (rather than, or in addition to, an effect on PKC), is effective in reducing or reversing resistance to doxorubicin, taxol and vinblastine in human tumour cells with a clinically relevant degree of MDR. However, results of in vivo experiments conducted to investigate the effects of Ro 32-2241 on resistance to doxorubicin suggest that it may not be possible to achieve sufficiently high levels of Ro 32-2241 in vivo to modulate MDR.

Ossification in the rectus sheath following free rectus flap.

Heterotopic ossification (HO) is a rare complication of laparotomy wounds. In this report, we describe an unusual presentation of ossification within the closed sheath following the harvest of a free rectus flap for lower limb reconstruction. Of specific interest to this case is that access to the rectus was gained through a lower transverse approach. Furthermore, the extremities of this incision were utilised for harvest of cancellous bone from the iliac crests. Given that one explanation for HO is intraoperative seeding it is of note that no problem was encountered in the wound intimately associated with the bony disruption.

Sub-lethal effects of exposing the human melanoma cell line SKmel-23 to 532 nm laser light.

The human melanoma cell line SKmel-23 has been used to investigate the sub-lethal damage that can occur as a result of exposing melanin containing cells to light (532 nm) from a frequency doubled Q-switched (Nd:YAG) laser. A dose response curve was obtained, which indicates that at energy levels of 0.6 J/cm2 and below no effect on either the viability or growth rate of the cell line was observed. Above this, cells rapidly died and at an energy level of 2.0 J/cm2, only approximately 15% of cells survived. This contrasts with the effects on the G361 melanoma line, which contains far less melanosomes, as an LD50 for this cell line was approximately 5.5 J/cm2. Exposing SKmel-23 cells to 0.4 J/cm2 of 532 nm light results in a diminution of the number of melanosomes within cells as well as a marked decrease in melanin content, as determined by spectrophotometric assay and electron microscopy. Using the reverse transcriptase polymerase chain reaction technique, the reduction in melanin content of the cells was accompanied by a selective decrease in mRNA coding for tyrosinase, the first enzyme in the biosynthetic pathway for melanin. No decrease in the mRNA coding for the GAPDH protein was observed. Our finding has implications for understanding the control processes that regulate the melanin content of cells and suggests that the model described can be used to further investigate changes that may occur in cells as a result of their exposure to sub-lethal levels of laser light.

Cutaneous malignant melanoma in the young.

Between the years 1967 and 1993, 3246 patients were diagnosed with malignant melanoma at Frenchay Hospital, Bristol. This paper reports 47 patients, 21 years of age or under, including 10 preadolescent cases under 14 years of age. It represents a further follow-up of a cohort originally published from this centre in 1986 in addition to 18 new cases. Most (89%) of the lesions occurred on the trunk and extremities, with females showing a predominance of lesions on the lower limbs. 83% of the melanomas were of the superficial spreading type: 72% invaded to Clark level III and IV. Thickness ranged from 0.29 mm to 50.00 mm (median 1.20 mm). Ulceration was present in 17% of cases and 32% of melanomas arose within a pre-existing small congenital melanocytic naevus. Overall 5-year survival was 81%, with a mean follow-up of 8.5 years. Ulceration and tumour thickness of greater than 1.5 mm were associated with a poor prognosis.

Management of infant sleep problems in a residential unit.

Torrens House provides a short residential programme for families with a baby (8-12 months of age) identified by parents as having a sleep problem such as waking frequently at night and being difficult to settle. The programme involves the promotion of infant self-settling by the use of a controlled crying technique, together with wrapping, cessation of night feeds and establishment of a day-time routine. Twenty families (with 23 babies) were followed through the programme and for 3 months afterwards. There were significant decreases in the number of times the babies woke, the number of night-feeds and the length of time awake at night at 1 month follow-up, with a reduction in depressive symptomatology of the parents and a perceived improvement in their infants' behaviour. Twenty of the 23 babies were sleeping well at 3 month follow-up.

Regulation of messenger RNAs for the hydrophobic surfactant proteins in human lung.

The pulmonary surfactant proteins SP-B (8,000 D) and SP-C (4,000 D) accelerate surface film formation by surfactant phospholipids. We used cDNA probes to examine regulation of these proteins in human fetal lung. The mRNAs were detectable at 13 wk gestation and increased to approximately 50% (SP-B) and approximately 15% (SP-C) of adult levels at 24 wk. The mRNAs were detected only in lung of 11 dog tissues examined. When human fetal lung was cultured as explants without hormones, SP-B mRNA increased and SP-C mRNA decreased. Exposure for 48 h to glucocorticoids, but not other steroids, increased both SP-B mRNA (approximately 4-fold) and SP-C mRNA (approximately 30-fold) vs. controls. Half-maximal stimulation occurred with 1 nM dexamethasone and 300 nM cortisol for SP-B mRNA and at three- to fivefold higher concentrations for SP-C mRNA. Both stimulation and its reversal on removal of hormone were more rapid for SP-B than for SP-C. Terbutaline and forskolin increased SP-B mRNA but not SP-C mRNA. Levels of both mRNAs were much higher in type II cells than fibroblasts prepared from explants. Thus, the genes for SP-B and SP-C are expressed in vivo before synthesis of both SP-A (28,000-36,000 D) and surfactant lipids. Glucocorticoid induction of SP-B and SP-C mRNAs in type II cells appears to be receptor mediated but may involve different mechanisms.

Low molecular weight human pulmonary surfactant protein (SP5): isolation, characterization, and cDNA and amino acid sequences.

Pulmonary surfactant is a lipid-protein complex that promotes alveolar stability by lowering the surface tension at the air-fluid interface in the peripheral air spaces. A group of hydrophobic surfactant-associated proteins has been shown to be essential for rapid surface film formation by surfactant phospholipids. We have purified a hydrophobic surfactant protein of approximately 5 kDa that we term SP5 from bronchopulmonary lavage fluid from a patient with alveolar proteinosis and shown that it promotes rapid surface film formation by simple mixtures of phospholipids. We have derived the full amino acid sequence of human SP5 from the nucleotide sequence of cDNAs identified with oligonucleotide probes based on the NH2-terminal sequence of SP5. SP5 isolated from surfactant is a fragment of a much larger precursor protein (21 kDa). The precursor contains an extremely hydrophobic region of 34 amino acids that comprises most of the mature SP5. This hydrophobicity explains the unusual solubility characteristics of SP5 and the fact that it is lipid-associated when isolated from lung.

DNA analysis for antenatal diagnosis of thalassaemia and haemophilia.

Two years' experience with DNA analysis for the antenatal diagnosis of thalassaemia and haemophilia is described. The advantages of DNA testing, including a first-trimester diagnosis and greater availability, must be considered in relation to the problems that are associated with this procedure. In particular, the risk of recombination in DNA polymorphism studies should be understood and explained fully to the patient.

Clinical experience with 50 cases of first-trimester fetal diagnosis by chorionic biopsy.

Prenatal diagnosis by chorionic biopsy was undertaken between the eighth and 12th weeks of pregnancy in 50 patients at risk of chromosomal or genetic abnormalities. Samples from 45 patients were karyotyped. A DNA analysis for the detection of homozygous beta-thalassaemia was undertaken in five patients. The sample from one patient at risk of haemophilia in the fetus was subjected to DNA analysis after a male fetus was confirmed on karyotyping. Abnormal karyotypes were detected in four fetuses while three had homozygous beta-thalassaemia.

High-productivity alcohol fermentations using Zymomonas mobilis.

A process is under development at the University of New South Wales to produce fermentation ethanol faster and more efficiently. The process is based on the micro-organism Zymomonas mobilis, which has higher specific rates of ethanol production and higher yields when compared with the traditionally used yeasts. By using hollow fibre membranes for cell recycle, high productivity continuous processes have been studied at laboratory-scale. Pilot scale evaluations (500 litres) are now in progress through Licence Agreements between the University and industry. Genetic manipulation and recombinant DNA techniques are being used to increase the ethanol tolerance and broaden the substrate range. Most recently glucoamylase genes from Aspergillus niger have been cloned into Escherichia coli K12 as part of a programme to enable direct fermentation of starch to ethanol by Z. mobilis.