This is the first book to comprehensively cover chromatic polynomials of graphs. It includes most of the known results and unsolved problems in the area of chromatic polynomials. Dividing the book ...into three main parts, the authors take readers from the rudiments of chromatic polynomials to more complex topics: the chromatic equivalence classes of graphs and the zeros and inequalities of chromatic polynomials. The early material is well suited to a graduate level course while the latter parts will be an invaluable resource for postgraduate students and researchers in combinatorics and graph theory.
Improving wastewater treatment processes is becoming increasingly important, due to more stringent effluent quality requirements, the need to reduce energy consumption and chemical dosing. This can ...be achieved by applying artificial intelligence. Machine learning is implemented in two domains: (1) predictive control and (2) advanced analytics. This is currently being piloted at the integrated validation plant of PUB, Singapore's National Water Agency. (1) Primarily, predictive control is applied for optimised nutrient removal. This is obtained by application of a self-learning feedforward algorithm, which uses load prediction and machine learning, fine-tuned with feedback on ammonium effluent. Operational results with predictive control show that the load prediction has an accuracy of ≈88%. It is also shown that an up to ≈15% reduction of aeration amount is achieved compared to conventional control. It is proven that this load prediction-based control leads to stable operation and meeting effluent quality requirements as an autopilot system. (2) Additionally, advanced analytics are being developed for operational support. This is obtained by application of quantile regression neural network modelling for anomaly detection. Preliminary results illustrate the ability to autodetect process and instrument anomalies. These can be used as early warnings to deliver data-driven operational support to process operators.
Familial multiple intestinal atresias is an autosomal recessive disease with or without combined immunodeficiency. In the last year, several reports have described mutations in the gene TTC7A as ...causal to the disease in different populations. However, exact correlation between different genotypes and various phenotypes are not clear. In this study, we report identification of novel compound heterozygous mutations in TTC7A gene in a Malay girl with familial multiple intestinal atresias and severe combined immunodeficiency (MIA‐SCID) by whole exome sequencing. We found two mutations in TTC7A: one that destroyed a putative splicing acceptor at the junction of intron 17/exon 18 and one that introduced a stop codon that would truncate the last two amino acids of the encoded protein. Reviewing the recent reports on TTC7A mutations reveals correlation between the position and nature of the mutations with patient survival and clinical manifestations. Examination of public databases also suggests carrier status for healthy individuals, making a case for population screening on this gene, especially in populations with suspected frequent founder mutations.
Current literature reports varied significance of ulnar styloid fractures (USF) associated with distal radius fractures. Our study assesses the role of ulnar styloid fractures and fragment size in ...surgically managed distal radius fractures.
We reviewed patients who underwent surgical fixation of distal radius fractures between January 2004 to June 2006. Patients were divided into those with (Group 1) and without (Group 0) USFs. Post-operative radiographic parameters, clinical outcomes and overall wrist function were analysed. Outcomes included ulnar-sided wrist pain, extensor carpi ulnaris (ECU) tendinitis, triangular fibrocartilage complex (TFCC) grind test, distal radioulnar joint (DRUJ) instability and pain. Overall wrist function was assessed with range of motion and Disabilities of the Arm, Shoulder and Hand (DASH) score.
Our study cohort included 31 males and 23 females, and 38.9% of these patients had concomitant USFs. There was no difference in terms of demographic data and fracture configuration between groups. Radiographic parameters were similar, except for palmar tilt, which was significantly higher in Group 1 (4.6º vs 9.4º, p=0.047). At 24 months, there were no differences in clinical outcomes and overall wrist function. A sub-group analysis showed that mean USF fragment size was larger in patients with a positive TFCC grind test (3.9mm vs 7.3mm, p=0.033).
The presence of USFs in surgically managed distal radius fractures does not compromise clinical and functional outcome. Similarly, the size of USFs does not impact clinical and functional outcome but is associated with the presence of a positive TFCC grind test.
Unicompartmental knee arthroplasty (UKA) is an alternative to total knee arthroplasty for patients who require treatment of single-compartment osteoarthritis, especially for young patients. To ...satisfy this requirement, new patient-specific prosthetic designs have been introduced. The patient-specific UKA is designed on the basis of data from preoperative medical images. In general, knee implant design with increased conformity has been developed to provide lower contact stress and reduced wear on the tibial insert compared with flat knee designs. The different tibiofemoral conformity may provide designers the opportunity to address both wear and kinematic design goals simultaneously. The aim of this study was to evaluate wear prediction with respect to tibiofemoral conformity design in patient-specific UKA under gait loading conditions by using a previously validated computational wear method.
Three designs with different conformities were developed with the same femoral component: a flat design normally used in fixed-bearing UKA, a tibia plateau anatomy mimetic (AM) design, and an increased conforming design. We investigated the kinematics, contact stress, contact area, wear rate, and volumetric wear of the three different tibial insert designs.
Conforming increased design showed a lower contact stress and increased contact area. In addition, increased conformity resulted in a reduction of the wear rate and volumetric wear. However, the increased conformity design showed limited kinematics.
Our results indicated that increased conformity provided improvements in wear but resulted in limited kinematics. Therefore, increased conformity should be avoided in fixed-bearing patient-specific UKA design. We recommend a flat or plateau AM tibial insert design in patient-specific UKA.
: Y-G. Koh, K-M. Park, H-Y. Lee, K-T. Kang. Influence of tibiofemoral congruency design on the wear of patient-specific unicompartmental knee arthroplasty using finite element analysis.
2019;8:156-164. DOI: 10.1302/2046-3758.83.BJR-2018-0193.R1.
In the gastrointestinal tract, phasic contractions are caused by electrical activity termed slow waves. Slow waves are generated and actively propagated by interstitial cells of Cajal (ICC). The ...initiation of pacemaker activity in the ICC is caused by release of Ca2+ from inositol 1,4,5-trisphosphate (IP3) receptor-operated stores, uptake of Ca2+ into mitochondria, and the development of unitary currents. Summation of unitary currents causes depolarization and activation of a dihydropyridine-resistant Ca2+ conductance that entrains pacemaker activity in a network of ICC, resulting in the active propagation of slow waves. Slow wave frequency is regulated by a variety of physiological agonists and conditions, and shifts in pacemaker dominance can occur in response to both neural and nonneural inputs. Loss of ICC in many human motility disorders suggests exciting new hypotheses for the etiology of these disorders.
Activation of the extensive cross-talk among the receptor tyrosine kinases (RTKs), particularly ErbB family-Met cross-talk, has emerged as a likely source of drug resistance. Notwithstanding ...brilliant successes were attained while using small-molecule inhibitors or antibody therapeutics against specific RTKs in multiple cancers over recent decades, a high recurrence rate remains unsolved in patients treated with these targeted inhibitors. It is well aligned with multifaceted properties of cancer and cross-talk and convergence of signaling pathways of RTKs. Thereby many therapeutic interventions have been actively developed to overcome inherent or acquired resistance. To date, no bispecific antibody (BsAb) showed complete depletion of dual RTKs from the plasma membrane and efficient dual degradation. In this manuscript, we report the first findings of a target-specific dual internalization and degradation of membrane RTKs induced by designed BsAbs based on the internalizing monoclonal antibodies and the therapeutic values of these BsAbs. Leveraging the anti-Met mAb able to internalize and degrade by a unique mechanism, we generated the BsAbs for Met/epidermal growth factor receptor (EGFR) and Met/HER2 to induce an efficient EGFR or HER2 internalization and degradation in the presence of Met that is frequently overexpressed in the invasive tumors and involved in the resistance against EGFR- or HER2-targeted therapies. We found that Met/EGFR BsAb ME22S induces dissociation of the Met-EGFR complex from Hsp90, followed by significant degradation of Met and EGFR. By employing patient-derived tumor models we demonstrate therapeutic potential of the BsAb-mediated dual degradation in various cancers.
Background
Involvement of the lateral compartment remains a relative or absolute contraindication to pelvic exenteration in most units. Initial experience with exenteration in the authors' unit ...produced a 21 per cent clear margin rate (R0), which improved to 53 per cent by adopting a novel technique for en bloc resection of the iliac vessels and other side‐wall structures. The objective of this study was to report morbidity and oncological outcomes in consecutive exenterations involving the lateral compartment.
Methods
Patients undergoing pelvic exenteration between 1994 and 2014 were eligible for review.
Results
Two hundred consecutive patients who had en bloc resection of the lateral compartment were included. R0 resection was achieved in 66·5 per cent of 197 patients undergoing surgery for cancer and 68·9 per cent of planned curative resections. For patients with colorectal cancer, a clear resection margin was associated with a significant overall survival benefit (P = 0·030). Median overall and disease‐free survival in this group was 41 and 27 months respectively. Overall 1‐, 3‐ and 5‐year survival rates were 86, 46 and 35 per cent respectively. No predictors of survival were identified on univariable analysis other than margin status and operative intent. Excision of the common or external iliac vessels or sciatic nerve did not confer a survival disadvantage.
Conclusion
The continuing evolution of radical pelvic exenteration techniques has seen an improvement in R0 margin status from 21 to 66·5 per cent over a 20‐year interval by routine adoption of a more lateral anatomical plane. Five‐year overall survival rates are comparable with those for more centrally based tumours.
Extension of excision confers survival advantage
Although outbreaks of Mycobacterium abscessus infection have been reported, none of these reports has identified the potential sources of infection and modes of transmission. In April 2008, we ...identified and investigated an outbreak of M. abscessus skin and soft tissue infections following acupuncture among the patients who visited an oriental medical clinic. Active surveillance of patients who had visited the clinic was conducted to define the extent of the outbreak. Environmental cultures and a case–control study were performed to elucidate the source of infection and mode of transmission. From 1002 patients interviewed, 109 patients were identified as having suffered M. abscessus skin and soft tissue infections at acupuncture sites. A single strain of M. abscessus was isolated from the wounds of 31 patients and nine environmental samples, including a diluted glutaraldehyde solution. The case–control study revealed that a higher numbers of visits to the clinic for acupuncture (adjusted OR (aOR) 20.12; 95% CI 4.34–93.35) and the use of interferential current therapy or low-frequency therapy (aOR 36.12; 95% CI 5.54–235.44) were associated with the development of M. abscessus infection. The contaminated diluted glutaraldehyde solution that was used to disinfect the physical therapy devices may have been the source of the outbreak of M. abscessus infection in the 109 patients who underwent acupuncture.
Summary
Despite ethnic differences in cortisol sensitivity, only one study in Caucasians has assessed trabecular bone score (TBS) in patients with subclinical hypercortisolism (SH). We showed that ...both subtle cortisol excess and reduced adrenal androgen may contribute to impaired bone quality in Asian women with SH.
Introduction
One study in Caucasians has assessed trabecular bone score (TBS), an index of bone microstructure, in adrenal incidentaloma (AI) patients with subclinical hypercortisolism (SH). There are ethnic differences in cortisol sensitivities between Caucasian and Asian populations. We investigated the associations of cortisol and the adrenal androgen dehydroepiandrosterone-sulfate (DHEA-S) with TBS in AI patients with SH, adrenal Cushing’s syndrome (CS), and nonfunctional AI (NFAI).
Methods
We measured TBS, cortisol levels after the overnight 1 mg dexamethasone suppression test (1 mg DST), and cortisol/DHEA-S in 61 patients with SH (30 men; 31 women), 19 with adrenal CS (4 men; 15 women), and 355 with NFAI (213 men; 142 women).
Results
After adjusting for confounders, the serum cortisol level after 1 mg DST was inversely correlated with TBS in men (
β
= −0.133,
P
= 0.045) and women (
β
= − 0.140,
P
= 0.048). Higher cortisol/DHEA-S ratio was associated with lower TBS in women (
β
= − 0.252,
P
< 0.001), but not men. This inverse association of cortisol/DHEA-S ratio in women remained statistically significant after adjusting for the serum cortisol level after 1 mg DST (
β
= − 0.221,
P
= 0.008). Compared with women with NFAI, women with SH had 2.2% lower TBS (
P
= 0.040). Deteriorated bone microstructure (TBS < 1.230) was associated with the serum cortisol level after 1 mg DST (odds ratio OR, 2.18; 95% confidence interval CI, 1.04–4.53) and cortisol/DHEA-S ratio (OR, 2.05; 95% CI, 1.03–4.08).
Conclusions
Subtle cortisol excess in both genders and reduced DHEA-S, especially in women, may contribute to impaired bone quality in Asian patients with SH.
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