Predictors, costs and characteristics of out of area placement for people with intellectual disability and challenging behaviour

Background Out of area placements for people with challenging behaviour represent an expensive and often ineffective strategy for meeting the needs of this service user group. Methods More than 800 agencies and service settings in a large area of South Wales were screened to identify children and adults with challenging behaviour against a number of defined operational criteria. Detailed data on identified individuals and the services they received were collected by interviewing key informants. Univariate and multivariate statistics were employed to identify predictors of out of area placement. Results In total, 1458 people were identified. Full data were available for 901 participants, 97 of whom were placed out of area. Predictors of out of area placement included behaviours resulting in physical injury and exclusion from service settings, a history of formal detention under the mental health act, the presence of mental health problems, a diagnosis of autism and higher total score on the Adaptive Behaviour Scale. Out of area placements were typically of high cost, and associated with only limited evidence of improved service quality. Conclusions Identifying predictors for out of area placement can be used to highlight deficiencies in local services and individuals at increased risk of exclusion from local services.     

超细纤维乳管镜引导下乳管内肿瘤切除术

目的探讨超细纤维乳管镜引导下乳管内肿瘤切除术的应用价值。方法对312例乳头溢液进行乳管镜检查，其中乳管内发现肿瘤者行手术治疗。利用乳管镜冷光源的皮肤透照点定象限，乳管扩张器探针定乳管走行方向，亚甲蓝染色定乳管末梢的分布。结果78例导管内发现肿瘤：单发性乳头状瘤68例，乳头状瘤病5例，导管内癌5例。28．2％（22／78）的病灶位于总导管，48．7％（38／78）位于导管Ⅰ级分支，17．9％（14／78）位于Ⅱ级分支，位于Ⅲ级和Ⅳ级分支病灶仅占3．8％（3／78）和1．3％（1／78）。病灶距乳头开口的平均距离为2．5cm（1～5cm）。78例均行手术治疗。术后病理诊断证实：65例乳头状瘤，8例乳头状瘤病，5例为导管内癌。乳管镜诊断符合率：乳头状瘤96％（65／68），乳头状瘤病100％（5／5），导管内癌100％（5／5）。单纯导管切除术65例，区段切除术8例，保乳根治术3例，改良根治术2例。结论通过光、针、色三位一体的方法定位以最小的切除范围达到最准确的切除目的，实现乳管内肿瘤的微创治疗。     

Sterile surgical technique for shunt placement reduces the shunt infection rate in children: preliminary analysis of a prospective protocol in 115 consecutive procedures

Objective The objective of this study was to evaluate whether the rigid application of a sterile protocol for shunt placement was applicable on a routine basis and allowed the reduction of shunt infections (SI) in children. Materials and methods Since 2001, a rigid sterile protocol for shunt placement in children using neither antibiotic-impregnated catheters nor laminar airflow was prospectively applied at Erasme Hospital, Brussels, Belgium. For assessing the protocol efficacy before continuation, we preliminarily analyzed the results of the first 100 operated children (43 females, 57 males, 49 aged <12 months; 115 consecutive shunt placement/revision procedures). All procedures were performed by the same senior surgeon, one assistant, one circulating nurse, one anesthesiologist. The sterile protocol was rigidly imposed to these four staff members: uniformed surgical technique; limited implant and skin edge manipulation; minimized human circulation in the room; scheduling surgery as first morning operation; avoiding postoperative cerebrospinal fluid (CSF) leak; double gloving; procedures of less than 30-min duration; systemic antibiotics prophylaxis. We analyzed separately: (1) children carrying an increased risk of SI (n = 38) due to preoperative external ventricular drainage, CSF leak, meningitis, glucocorticoids, chemotherapy; (2) children aged <12 months; (3) procedures for shunt revision. Results Errors in protocol application were recorded in 71/115 procedures. They were mainly done by non-surgical staff, decreased with time and were medically justified in some young children. Surprisingly, no SI occurred (follow-up, 4 to 70 months). One child developed an appendicitis with peritonitis (Streptococcus faecalis) after 6 months. No SI was found. After peritonitis was cured, shunt reinsertion was uneventful. Conclusion These preliminary results suggest that a uniform and drastic sterile surgical technique for shunt placement: (1) can be rigidly applied on a routine basis; (2) can lower the early SI rate below 1%; (3) might have a stronger impact to reduce SI than using antibiotic-impregnated catheters and optimizing the operative environment such as using laminar airflow and reducing the non-surgical staff. This last issue will be evaluated further in the present ongoing protocol.     

早期乳腺导管原位癌X线表现与预后生物学标记关系的研究

目的评价乳腺导管原位癌（DCIS）及DCIS伴微浸润的X线片表现，分析X线表现与预后生物学标记的相关性。方法对50例乳腺DCIS及45例DCIS伴微浸润的患者行X线检查，共62例行预后生物学标记，分析影像表现与孕激素受体（PR）、癌基因（C—erbB-2）、抑癌基因（p53）的相关性。用卡方检验进行统计学处理，并对有意义者行优势比（OR值）分析。结果（1）单独1个X线征象表现者62例；合并2个征象26例；阴性7例。（2）各种X线征象单独分析显示，62例有钙化的病灶中恶性钙化占73％（45例），其余为中间性钙化；钙化以簇状分布最为常见（36例），其次为段样分布（18例）。22例有肿块的病灶中，以卵圆形肿块最为常见（13例）；肿块的边缘表现为浸润、小分叶、清晰和模糊各为15、1、4和2例；等密度肿块占的比例较高（55％，12例）。结构扭曲7例，除1例外多与其他征象伴行；局灶性不对称占16％（15／95），可单独发生或与其他征象伴发。（3）将病灶的X线表现分成恶性钙化、中间性钙化和非钙化3组，PR与C-erbB-2在3组中的分布有统计性意义，PR阳性表达者X线上非钙化征象发生率是中间性钙化的11．00倍[χ^2=8．571，P=0．003；95％可信区间（CI）为1．998～60．572]、恶性钙化的8．80倍（χ^2=9．748，P=0．002；95％CI为2．024～38．253）；而C—erbB-2高表达者，恶性钙化是非钙化发生的12．35倍（χ^2=7．353，P=0．007；95％CI为1．447—105．443），中间性钙化的5．74倍（χ^2=4．977，P=0．026；95％CI为1．110～29．645）。结论乳腺DCIS及DCIS伴微浸润X线征象有特征。X线征象可以作为早期乳腺DCIS的一个预后因子。     

Mixed H2/H∞ control with pole placement in a class of regions

The problem of mixed H₂/H_∞ control with pole placement is considered for linear time-invariant systems. This is the problem of determining a controller for linear time-invariant systems which minimizes the H₂-norm of a certain closed-loop transfor function subject to an H_∞-norm constraint on another closed-loop transfer function and an additional constraint on the location of the closed-loop poles in the complex plane. An optimization problem is posed for the pole-constrained H₂/H_∞, problem in such a way that the objective function is expressed as a weighted sum of the actual H₂ cost and its upper bound. A necessary condition for the optimization problem is derived via the Lagrange multiplier technique. The condition involves a set of highly coupled equations. By sacrificing the H₂ performance, an alternative optimization problem is posed in order to simplify the necessary condition. An iterative algorithm for solving the coupled equations arising in the necessary conditions is proposed and numerical examples are presented.     

Expression of oncogene products, anti-oncogene products and oncofetal antigens in intraductal papillary-mucinous neoplasm of the pancreas

A few previous studies have demonstrated the expression or mutations of oncogenes and anti-oncogenes as well as that of oncofetal antigens in intraductal papillary-mucinous neoplasm of the pancreas. In this study, we have investigated the immunohistochemical expression of oncogene (ras and c-erbB-2) and anti-oncogene (p53 and retinoblastoma [Rb]) products and oncofetal antigens (CEA, CA19-9 and DUPAN-2) in nine such tumours of the pancreas. In normal pancreas (5 cases), the Rb gene product and CA19-9 were expressed in all cases, while ras and c-erbB-2 gene products, p53 protein, CEA and DUPAN-2 were not expressed. In intraductal papillary-mucinous tumours (n = 9), ras, c-erbB-2, p53 and Rb gene products were present in 4/9 (44%), 7/9 (78%), 0.9 (0%) and 6/9 (67%) cases, respectively. CEA, CA19-9 and DUPAN-2 were expressed in 8/9 (89%), 9/9 (100%) and 2/9 (22%) cases respectively. In invasive ductal adenocarcinoma of the pancrease (7 cases), ras, c-erbB-2, p53 and Rb gene products were expressed in 3/7 (43%), 6/7 (86%), 2/7 (29%) and 3/ & (43%) cases respectively. CEA, CA19-9 and DUPAN-2 were expressed in 7/7 (100%), 7/7 (100%) and 6/7 (86%) cases, respectively. The extent and intensity of the expression of these antigens was greater in invasive ductal adenocarcinomas. These data suggest that activation of ras and c-erbB-2 oncogenes and inactivation of Rb anti-oncogene may contribute to the development and progression of intraductal papillary-mucinous tumours of the pancreas and that there is neo-expression of CEA and DUPAN-2 during the development and progression of these tumours.     

p53 protein expression and nuclear DNA content in breast intraductal proliferations

Immunohistochemical analysis of the p53 gene protein and cytometric assessment of nuclear DNA were performed in a series of 51 cases of intraductal breast proliferation. The series included 22 cases of intraductal hyperplasia without atypia, 6 cases of intraductal hyperplasia with atypia, and 23 cases of pure intraductal carcinoma. Expression of p53 protein was detected in one case of intraductal hyperplasia without atypia (4·5 per cent), one case of intraductal hyperplasia with atypia (16·6 per cent) and six cases of intraductal carcinoma (26·0 per cent). No significant correlation was observed between p53 expression and histological subtype of intraductal carcinoma. Aneuploidy was demonstrated in two cases of intraductal hyperplasia with atypia (33·3 per cent) and in 18 cases of intraductal carcinoma (78·2 per cent). All cases of intraductal hyperplasia without atypia were euploid. No significant association was observed between p53 protein expression and ploidy in intraductal hyperplasia. The only case of intraductal hyperplasia without atypia positive for p53 was euploid, whereas the only p53-positive case of intraductal hyperplasia with atypia was aneuploid. Among the intraductal carcinomas, only the aneuploid cases showed positivity for p53, regardless of histological subtype. The results suggest that some of the changes observed in invasive breast carcinoma, such as p53 expression and aneuploidy, are already present in breast intraductal proliferation, especially in areas with atypia and in intraductal carcinoma. The expression of p53 in breast intraductal proliferation may reflect the acquisition of p53 gene mutations in cells unable adequately to repair DNA damage, with genomic instability which would lead to clonal expansion and putative evolution to invasive disease.     

Cyclooxygenase-2 expression: a potential prognostic and predictive marker for high-grade ductal carcinoma in situ of the breast

AIMS: To study cyclooxygenase-2 (COX-2) expression in ductal carcinoma in situ (DCIS) of the breast and its association with histological features. COX-2, an inducible prostaglandin synthase, has been shown to be important in mammary carcinogenesis, being associated with increased tumour size and unfavourable outcome in breast cancer. Animal studies indicate that COX-2 inhibition is effective in the prevention and treatment of mammary cancers. METHODS AND RESULTS: Fifty-one cases of DCIS diagnosed during 1990-2000 were reviewed. Immunohistochemistry for COX-2 was performed and the COX-2 staining scores were correlated with histological features. The majority of cases [41 of 51 (80%)] had positive COX-2 staining, of which 13 cases (25%) had strong staining. High nuclear grade DCIS was significantly associated with increased COX-2 staining (P = 0.04). CONCLUSIONS: High-grade lesions are known to be associated with a higher recurrence rate following excision and are often oestrogen receptor negative, and as such, may be less responsive to adjuvant tamoxifen therapy. There is a need to examine further the role of COX-2 expression in DCIS, as both a prognostic and predictive factor.     

Intraductal papillary-mucinous tumours represent a distinct group of pancreatic neoplasms: an investigation of tumour cell differentiation and K-ras,p53 and c-erbB-2 abnormalities in 26 patients

Intraductal papillary growth of mucin producting hypersecreting, columnar cells characterizes a group of rare pancreatic exocrine neoplasms which we propose to call intraductal papillary-mucinous tumors (IPMT). We analysed the histopathology of 26 IPMT in relation to gastro-enteropancreatic marker expression, genetic changes and biology. Four IPMT showing only mild dysplasia were considered to be adenomas. Nine tumours displayed moderate dysplasia and were regarded as borderline. Severe dysplasia-carcinoma in situ changes were found in 13 IPMT which were therefore classified as intraductal carcinomas. Six of these carcinomas were frankly invasive and two of these had lymph node metastases. The invasive component resembled mucinous noncystic carcinoma in all but one tumour which showed a ductal invasion pattern. Immunohistochemically, an intestinal marker type was found in most carcinomas, while gastric type differentiation prevailed among adenomas or borderline tumours. K-ras mutations (seven at codon 12 and one at codon 13) were found in 31% of IPMT (2 adenomas, 1 borderline, 5 carcinomas). Nuclear p53 overexpression was detected in 31% of IPMT (6 carcinomas and 2 borderline IPMT) and correlated with p53 mutations (one at exon 8 and the other at exon 5) in two carcinomas. p53 abnormalities were unrelated to K-ras mutation. c-erbB-2 overexpression was observed in 65% of IPMT, with various grades of dysplasia. Twenty-two of 24 patients are alive and well after a mean post-operative follow-up of 41 months. Only two patients, both with invasive cancer at the time of surgery, died of tumour disease. It is concluded that pancreatic IPMT encompass neoplasms which, in general, have a favorable prognosis, but are heterogeneous in regard to grade of dysplasia and marker expression. Adenoma, borderline tumour, intraductal carcinoma and invasive carcinoma can be differentiated. p53 changes but not K-ras mutation or c-erbB-2 overexpression are related to the grade of malignancy. Most IPMT differ in histological structure, marker expression and behaviour from ductal adenocarcinoma.     

Strategies and determinants for selection of alternate foot placement during human locomotion: influence of spatial and temporal constraints

During locomotion in a cluttered terrain, certain terrain surfaces such as an icy one are not appropriate for foot placement; an alternate choice is required. In a previous study we showed that the selection of foot placement is not random but systematic; the dominant choices made are not uniquely defined by the available or predicted sensory inputs. We argued that selection is guided by specific rules and involves minimal displacement of the foot from its normal landing spot. The experimental protocol involved implicit spatial constraint by requiring individuals to step on the force plate that could trigger a lighted area to be avoided, thereby requiring individuals to respond within one step-cycle. Alternate foot placement was visually identified, but not measured. The purpose of this study was to directly measure foot placement, validate and/or refine the rules used to guide selection, and identify whether the alternate foot placement choices are influenced by spatial and temporal constraints on response selection. The area to be avoided was visible from the start and therefore individuals could plan and implement appropriate avoidance strategies without any temporal constraint. Spatial constraint introduced in this experiment included requirement both to step on a specific location and to avoid stepping on a specific location on the next step. The results provide support for the rules previously identified in guiding foot placement to an alternate location. Minimal displacement of the foot from its normal landing spot was validated as an important factor for selecting alternate foot placement. When several choices satisfied this factor, additional factors guide alternate foot placement. Modifications in the plane of progression are preferred while stepping wide is avoided. When no temporal constraints are imposed on the response selection, enhancing forward progression of the body becomes the dominant determinant followed by stability and lastly by energy costs associated with the modifications. A decision algorithm for selecting foot placement is proposed based on these findings. It is clear that while visual input plays a critical role in guiding foot placement, it is not entirely based on reactive control. This has implications for implementing visually guided adaptive locomotion in legged robots.