Total knee arthroplasty patients using the in-home X10 machine fully recovered. No additional therapy required.

Following total knee arthroplasties patients using the X10 increased their quadriceps strength 120% at 30 days post-surgery compared to their pre-surgical baseline. This contrasts sharply with contrast studies outpatient physical therapy that show patients suffer a 50-60% quadriceps strength deficit at 30 days post-surgery. For X10 patients, the average range of motion at 30 days was 124° and at discharge it was 128° (mean 43 days). The trial involved a single surgeon and two groups. Group one (21 patients) used only the X10 for pre-habilitation and rehabilitation, while group two (20 patients) used X10 alone for pre-habilitation and then utilized the X10 plus home care plus outpatient physical therapy for rehabilitation. Adding home care and outpatient physical therapy did not improve outcomes compared to patients who utilized X10 alone. Our results show no significant difference between the two groups. Indicating that the X10 by itself is adequate to completely rehabilitation patients from total knee arthroplasties. Finally, we compared our results to those of Calatayud et al.1 who monitored two groups of patients, one group had only physical therapy for rehabilitation while the other group used physical therapy for both prehabilitation and rehabilitation. Our results were superior to Calatayud et al.1 for extension, flexion, and quadriceps strength; for each of these measures the X10 treatment groups improved over time, while the Calatayud et al.1 groups showed losses.

Intervention strategies for microbial therapeutics in cancer immunotherapy.

Immunotherapies have drastically improved clinical outcomes in a wide range of malignancies. Nevertheless, patient responses remain highly variable, and reliable biomarkers that predict responses accurately are not yet fully understood. Compelling evidence from preclinical studies and observational data from clinical cohorts have shown that commensal microorganisms that reside in the human gastrointestinal tract, collectively termed the 'microbiome', can actively modify responses to chemotherapeutic agents and immunotherapies by influencing host immunosurveillance. Notably, microbial correlates are largely context specific, and response signatures may vary by patient population, geographic location and type of anticancer treatment. Therefore, the incongruence of beneficial microbiome signatures across studies, along with an emerging understanding of the mechanisms underlying the interactions between the microbiome, metabolome and host immune system, highlight a critical need for additional comprehensive and standardized multi-omics studies. Future research should consider key host factors, such as diet and use of medication, in both preclinical animal models and large-scale, multicenter clinical trials. In addition, there is a strong rationale to evaluate the microbiome as a tumor-extrinsic biomarker of clinical outcomes and to test the therapeutic potential of derived microbial products (e.g. defined microbial consortia), with the eventual goal of improving the efficacy of existing anticancer treatments. This review discusses the importance of the microbiome from the perspective of cancer immunotherapies, and outlines future steps that may contribute to wide-ranging clinical and translational benefits that may improve the health and quality of life of patients with cancer.

Nitrogen oxidation consortia dynamics influence the performance of full-scale rotating biological contactors.

Ammonia oxidising microorganisms (AOM) play an important role in ammonia removal in wastewater treatment works (WWTW) including rotating biological contactors (RBCs). Environmental factors within RBCs are known to impact the performance of key AOM, such that only some operational RBCs have shown ability for elevated ammonia removal. In this work, long-term treatment performance of seven full-scale RBC systems along with the structure and abundance of the ammonia oxidising bacteria (AOB) and archaea (AOA) communities within microbial biofilms were examined. Long term data showed the dominance of AOB in most RBCs, although two RBCs had demonstrable shift toward an AOA dominated AOM community. Next Generation Sequencing of the 16S rRNA gene revealed diverse evolutionary ancestry of AOB from RBC biofilms while nitrite-oxidising bacteria (NOBs) were similar to reference databases. AOA were more abundant in the biofilms subject to lower organic loading and higher oxygen concentration found at the distal end of RBC systems. Modelling revealed a distinct nitrogen cycling community present within high performing RBCs, linked to efficient control of RBC process variables (retention time, organic loading and oxygen concentration). We present a novel template for enhancing the resilience of RBC systems through microbial community analysis which can guide future strategies for more effective ammonia removal. To best of the author's knowledge, this is the first comparative study reporting the use of next generation sequencing data on microbial biofilms from RBCs to inform effluent quality of small WWTW.

Changes in laboratory markers of thrombotic risk early in the first trimester of pregnancy may be linked to an increase in estradiol and progesterone.

BACKGROUND: Pregnant women are at increased risk of venous thrombosis compared to non-pregnant women. Epidemiological and laboratory data suggest that hypercoagulability begins in the first trimester but it is unknown exactly how early in pregnancy this develops. The mechanisms that result in a prothrombotic state may involve oestrogens and progestogens. METHODS: Plasma samples were taken prior to conception and five times in early pregnancy, up to Day 59 gestation, from 22 women undergoing natural cycle in vitro fertilization, who subsequently gave birth at term following a normal pregnancy. Thrombin generation, free Protein S, Ddimer, Fibrinogen, factor VIII, estradiol and progesterone were measured. To counter inter-individual variability, the change in laboratory measurements between the pre-pregnant and pregnant state were measured over time. RESULTS: Peak thrombin, Endogenous Thrombin Potential, Velocity Index and fibrinogen significantly increased, and free Protein S significantly decreased, from pre-pregnancy levels, by 32 days gestation. Ddimer and VIII significantly increased from pre-pregnancy levels by 59 days gestation. Estradiol significantly increased by Day 32 gestation with a non-significant increase of 67% by Day 24 gestation. Progesterone significantly increased by Day 32 gestation. Almost all laboratory markers of thrombosis correlated significantly with estradiol and progesterone. CONCLUSION: Our work is the first to demonstrate that the prothrombotic state develops very early in the first trimester. Laboratory markers of hypercoagulability correlate significantly with estradiol and progesterone suggesting these are linked to the prothrombotic state of pregnancy. Clinicians should consider commencing thromboprophylaxis early in the first trimester in women at high thrombotic risk.

'Twisting the lion's tail': Manipulationist tests of causation for psychological mechanisms in the occurrence of delusions and hallucinations.

Over the past 20 years the importance of psychological processes in psychosis has gained increasing attention. However, it is key to determine the causal status of these processes in order to inform understanding and identify treatment targets. Studies that directly manipulate a psychological mechanism provide the most robust causal evidence. This review evaluates for the first time the extent of manipulationist causal evidence for the role of specific psychological mechanisms in delusions and hallucinations. A systematic search identified controlled experiments or targeted interventions that both manipulated a specific psychological mechanism and measured the effect on individual psychotic experiences. Forty-three manipulationist studies were found of which 40 measured paranoia, 11 measured hallucinations, and two measured grandiosity. Twenty-eight studies were experiments and 15 were targeted intervention trials. Only 18 used clinical samples. Manipulation of the specified psychological mechanism was demonstrated in 35 cases. Of these, 28 found a subsequent change in a psychotic experience. Negative affect and related psychological processing in relation to paranoia have been most tested. There is a small body of direct causal evidence for the role of psychological mechanisms in psychotic experiences - that highlight important novel treatment directions - but the manipulationist approach has been used too infrequently.

Sleep duration and psychotic experiences in patients at risk of psychosis: A secondary analysis of the EDIE-2 trial.

Sleep disturbance is common among individuals at risk of psychosis, yet few studies have investigated the relationship between sleep disturbance and clinical trajectory. The Early Detection and Intervention Evaluation (EDIE-2) trial provides longitudinal data on sleep duration and individual psychotic experiences from a cohort of individuals at risk of psychosis, which this study utilises in an opportunistic secondary analysis. Shorter and more variable sleep was hypothesised to be associated with more severe psychotic experiences and lower psychological wellbeing. Mixed effect models were used to test sleep duration and range as predictors of individual psychotic experiences and psychological wellbeing over the 12-24 months (with assessments every 3 months) in 160 participants. Shorter sleep duration was associated with more severe delusional ideas and hallucinations cross-sectionally and longitudinally. The longitudinal relationships did not remain significant after conservative controls were added for the previous severity of psychotic experiences. No significant relationships were found between the sleep variables and other psychotic experiences (e.g. cognitive disorganisation), or psychological wellbeing. The results support a relationship between shorter sleep duration and delusional ideas and hallucinations. Future studies should focus on improving sleep disturbance measurement, and test whether treating sleep improves clinical trajectory in the at-risk group.

Links between psychotic and neurotic symptoms in the general population: an analysis of longitudinal British National Survey data using Directed Acyclic Graphs.

BACKGROUND: Non-psychotic affective symptoms are important components of psychotic syndromes. They are frequent and are now thought to influence the emergence of paranoia and hallucinations. Evidence supporting this model of psychosis comes from recent cross-fertilising epidemiological and intervention studies. Epidemiological studies identify plausible targets for intervention but must be interpreted cautiously. Nevertheless, causal inference can be strengthened substantially using modern statistical methods. METHODS: Directed Acyclic Graphs were used in a dynamic Bayesian network approach to learn the overall dependence structure of chosen variables. DAG-based inference identifies the most likely directional links between multiple variables, thereby locating them in a putative causal cascade. We used initial and 18-month follow-up data from the 2000 British National Psychiatric Morbidity survey (N = 8580 and N = 2406). RESULTS: We analysed persecutory ideation, hallucinations, a range of affective symptoms and the effects of cannabis and problematic alcohol use. Worry was central to the links between symptoms, with plausible direct effects on insomnia, depressed mood and generalised anxiety, and recent cannabis use. Worry linked the other affective phenomena with paranoia. Hallucinations were connected only to worry and persecutory ideation. General anxiety, worry, sleep problems, and persecutory ideation were strongly self-predicting. Worry and persecutory ideation were connected over the 18-month interval in an apparent feedback loop. CONCLUSIONS: These results have implications for understanding dynamic processes in psychosis and for targeting psychological interventions. The reciprocal influence of worry and paranoia implies that treating either symptom is likely to ameliorate the other.

Fifty years of colic surgery.

Colic surgery is one of few treatments in which a veterinarian can use a skill to save an animal's life from a deadly disease within a short timeframe. Unfortunately, such success is not achieved without considerable risk for surgical failure, which is responsible for most complications in the immediate post-operative period. The last 50 years have witnessed considerable improvements in colic surgery, although a ranking of the most important ones might not meet with universal agreement. Teamwork plays a critical role in the final outcome, starting and finishing with the referring veterinarian and owner. These individuals are responsible for promptly transferring the horse to a surgical facility and then dealing with aftercare and delayed complications. The surgeon is responsible for the intervening steps, including the decision on the need for surgery, and works with the anaesthesiologist to help a metabolically challenged patient to tolerate surgery and anaesthesia. Although early referral and improved diagnostic procedures can have a positive influence on survival, perceived improvements in surgery and anaesthesia need to be reviewed with some circumspection. Although more rigorous definitions and statistical analyses used in recent studies can invalidate comparisons with older studies, complication rates appear to be on the rise, despite putative improvements in dealing with them. This trend tends to diminish the value of colic surgery through increasing costs, overreliance on post-operative pharmacological management, growing pessimism, high rates of intraoperative euthanasia, and possibly reduced long-term survival. Future efforts should address these concerns, mostly through emphasis on prompt referral, good surgical technique and reducing the cost of colic surgery to an affordable level that saves more lives.

Normal pregnancy is associated with an increase in thrombin generation from the very early stages of the first trimester.

BACKGROUND: Pregnancy is a hypercoagulable state associated with an increased risk of venous thrombosis, which begins during the first trimester, but the exact time of onset is unknown. Thrombin generation, a laboratory marker of thrombosis risk, increases during normal pregnancy but it is unclear exactly how early this increase occurs. METHODS: We assessed thrombin generation by Calibrated Automated Thrombography in women undergoing natural cycle in vitro fertilization, who subsequently gave birth at term following a normal pregnancy (n=22). Blood samples were taken just prior to conception and repeated five times during very early pregnancy, up to Day 59 estimated gestation. RESULTS: Mean Endogenous Thrombin Potential (ETP), peak thrombin generation and Velocity Index (VI) increased significantly from pre-pregnancy to Day 43 gestation (p=0.024-0.0004). This change persisted to Day 59 gestation. The mean of the percentage change from baseline, accounting for inter-individual variation, in ETP, peak thrombin and VI increased significantly from pre-pregnancy to Day 32 gestation (p=0.0351-<0.0001) with the mean increase from baseline persisting to Day 59 gestation. CONCLUSION: Thrombin generation increases significantly during the very early stages of normal pregnancy when compared to the pre-pregnancy state. The increased risk of venous thrombosis therefore likely begins very early in a woman's pregnancy, suggesting that women considered clinically to be at high thrombotic risk should start thromboprophylaxis as early as possible after a positive pregnancy test.

Virtual reality in the assessment, understanding, and treatment of mental health disorders.

Mental health problems are inseparable from the environment. With virtual reality (VR), computer-generated interactive environments, individuals can repeatedly experience their problematic situations and be taught, via evidence-based psychological treatments, how to overcome difficulties. VR is moving out of specialist laboratories. Our central aim was to describe the potential of VR in mental health, including a consideration of the first 20 years of applications. A systematic review of empirical studies was conducted. In all, 285 studies were identified, with 86 concerning assessment, 45 theory development, and 154 treatment. The main disorders researched were anxiety (n = 192), schizophrenia (n = 44), substance-related disorders (n = 22) and eating disorders (n = 18). There are pioneering early studies, but the methodological quality of studies was generally low. The gaps in meaningful applications to mental health are extensive. The most established finding is that VR exposure-based treatments can reduce anxiety disorders, but there are numerous research and treatment avenues of promise. VR was found to be a much-misused term, often applied to non-interactive and non-immersive technologies. We conclude that VR has the potential to transform the assessment, understanding and treatment of mental health problems. The treatment possibilities will only be realized if - with the user experience at the heart of design - the best immersive VR technology is combined with targeted translational interventions. The capability of VR to simulate reality could greatly increase access to psychological therapies, while treatment outcomes could be enhanced by the technology's ability to create new realities. VR may merit the level of attention given to neuroimaging.

Identification of Balance Deficits in People with Parkinson Disease; is the Sensory Organization Test Enough?

BACKGROUND AND PURPOSE: Balance deficits in people with Parkinson's disease can affect any of the multiple systems encompassing balance control. Thus, identification of the specific deficit is crucial in customizing balance rehabilitation. The sensory organization test, a test of sensory integration for balance control, is sometimes used in isolation to identify balance deficits in people with Parkinson's disease. More recently, the Mini-Balance Evaluations Systems Test, a clinical scale that tests multiple domains of balance control, has begun to be used to assess balance in patients with Parkinson's disease. The purpose of our study was to compare the use of Sensory Organization Test and Mini-Balance Evaluations Systems Test in identifying balance deficits in people with Parkinson's disease. METHODS: 45 participants (27M, 18F; 65.2 ± 8.2 years) with idiopathic Parkinson's disease participated in the cross-sectional study. Balance assessment was performed using the Sensory Organization Test and the Mini-Balance Evaluations Systems Test. People were classified into normal and abnormal balance based on the established cutoff scores (normal balance: Sensory Organization Test >69; Mini-Balance Evaluations Systems Test >73). RESULTS: More subjects were classified as having abnormal balance with the Mini-Balance Evaluations Systems Test (71% abnormal) than with the Sensory Organization Test (24% abnormal) in our cohort of people with Parkinson's disease. There were no subjects with a normal Mini-Balance Evaluations Systems Test score but abnormal Sensory Organization Test score. In contrast, there were 21 subjects who had an abnormal Mini-Balance Evaluations Systems Test score but normal Sensory Organization Test scores. DISCUSSION AND CONCLUSIONS: Findings from this study suggest that investigation of sensory integration deficits, alone, may not be able to identify all types of balance deficits found in patients with Parkinson's disease. Thus, a comprehensive approach should be used to test of multiple balance systems to provide customized rehabilitation.

A noninvasive mechanical treatment to reduce the visible appearance of cellulite.

Cellulite is a cosmetic condition of subcutaneous fat herniation through fibrous connective tissue that results in a dimpled appearance of the skin. Occurring in approximately 85% to 90% of all women worldwide, cellulite has been well studied. The result has been the development of a plethora of treatment protocols yielding little to no success. We describe a noninvasive mechanical treatment for women with cellulite, evaluating the safety and effectiveness of a technique that utilizes a unique patented device for the reduction of the visible appearance of cellulite.

Anatomical variations in epididymal-testicular fusion in stallions and their possible clinical significance.

REASONS FOR PERFORMING STUDY: Fusion anomalies of the epididymis with the testis may be clinically relevant in horses. However, anatomical variations in epididymal-testicular fusion have not been classified, and their clinical significance is unknown. OBJECTIVES: To describe anatomical variations and clinical significance of epididymal-testicular fusion in stallions. STUDY DESIGN: Anatomical study of testes from castrations, and description of 2 clinical cases with atypical epididymal-testicular fusion. METHODS: A total of 104 testes were obtained from equine castrations. Eight patterns of epididymal-testicular fusion were identified. Two clinical cases with epididymal dislocation were also described. RESULTS: Close attachment of the entire epididymis to the testis was the most common pattern of fusion (40%). Ninety-five per cent of cryptorchid testes and 34% of scrotal testes in the studied sample had elongated proper ligaments of the testes. Dislocation of the epididymal tail was observed in 2 stallions that had atypically long proper ligaments inserted on the dorsal aspect of the testes. CONCLUSIONS: Patterns of epididymal-testicular fusion can vary in stallions. Elongated proper ligaments of the testes occur mostly in cryptorchid testes but are also found in stallions with scrotal testes. Epididymal dislocation may develop in stallions with long proper ligaments that are inserted dorsally on the testes.

Anatomy of the vestibule of the omental bursa and epiploic foramen in the horse.

REASONS FOR PERFORMING STUDY: Epiploic foramen entrapment (EFE) is a common cause of colic in horses and available anatomical descriptions of this foramen and the associated vestibule of the omental bursa tend to be inconsistent, contradictory and inaccurate. OBJECTIVES: To describe the anatomy of the vestibule of the omental bursa and epiploic foramen. STUDY DESIGN: Dissection of 21 fresh equine cadavers shortly after euthanasia. METHODS: The anatomy of the vestibule of the omental bursa, epiploic foramen and related structures in the cranial abdomen were examined in situ and after removal from the abdomen. Photographs were taken and illustrations rendered to bring the relationship of the different folds, ligaments and organs involved into a 3D concept. RESULTS: The entrance into the vestibule and the passageway through it to the epiploic foramen is bounded by the gastropancreatic fold dorsally, caudally and ventrally. This fold constitutes the caudoventral boundary of the epiploic foramen along with the portal vein cranially and ventrally. The craniodorsal boundary of the epiploic foramen is formed by the caudate lobe of the liver. CONCLUSIONS: The gastropancreatic fold plays a more important role in the anatomy of the vestibule of the omental bursa and the epiploic foramen than has been documented in the most widely used anatomy textbooks written in English. Because of the importance of EFE in horses, information from this study about the relevant anatomy could provide a first step towards improved methods for treatment and laparoscopic prevention of these diseases.

Understanding jumping to conclusions in patients with persecutory delusions: working memory and intolerance of uncertainty.

BACKGROUND: Persecutory delusions are a key psychotic experience. A reasoning style known as 'jumping to conclusions' (JTC) - limited information gathering before reaching certainty in decision making - has been identified as a contributory factor in the occurrence of delusions. The cognitive processes that underpin JTC need to be determined in order to develop effective interventions for delusions. In the current study two alternative perspectives were tested: that JTC partially results from impairment in information-processing capabilities and that JTC is a motivated strategy to avoid uncertainty. METHOD: A group of 123 patients with persistent persecutory delusions completed assessments of JTC (the 60:40 beads task), IQ, working memory, intolerance of uncertainty, and psychiatric symptoms. Patients showing JTC were compared with patients not showing JTC. RESULTS: A total of 30 (24%) patients with delusions showed JTC. There were no differences between patients who did and did not jump to conclusions in overall psychopathology. Patients who jumped to conclusions had poorer working memory performance, lower IQ, lower intolerance of uncertainty and lower levels of worry. Working memory and worry independently predicted the presence of JTC. CONCLUSIONS: Hasty decision making in patients with delusions may partly arise from difficulties in keeping information in mind. Interventions for JTC are likely to benefit from addressing working memory performance, while in vivo techniques for patients with delusions will benefit from limiting the demands on working memory. The study provides little evidence for a contribution to JTC from top-down motivational beliefs about uncertainty.

Prevalence and spectrum of in utero structural brain abnormalities in fetuses with complex congenital heart disease.

BACKGROUND AND PURPOSE: Brain injury is a major complication in neonates with complex congenital heart disease. Preliminary evidence suggests that fetuses with congenital heart disease are at greater risk for brain abnormalities. However, the nature and frequency of these brain abnormalities detected by conventional fetal MR imaging has not been examined prospectively. Our primary objective was to determine the prevalence and spectrum of brain abnormalities detected on conventional clinical MR imaging in fetuses with complex congenital heart disease and, second, to compare the congenital heart disease cohort with a control group of fetuses from healthy pregnancies. MATERIALS AND METHODS: We prospectively recruited pregnant women with a confirmed fetal congenital heart disease diagnosis and healthy volunteers with normal fetal echocardiogram findings who underwent a fetal MR imaging between 18 and 39 weeks gestational age. RESULTS: A total of 338 fetuses (194 controls; 144 with congenital heart disease) were studied at a mean gestational age of 30.61 ± 4.67 weeks. Brain abnormalities were present in 23% of the congenital heart disease group compared with 1.5% in the control group (P < .001). The most common abnormalities in the congenital heart disease group were mild unilateral ventriculomegaly in 12/33 (36.4%) and increased extra-axial spaces in 10/33 (30.3%). Subgroup analyses comparing the type and frequency of brain abnormalities based on cardiac physiology did not reveal significant associations, suggesting that the brain abnormalities were not limited to those with the most severe congenital heart disease. CONCLUSIONS: This is the first large prospective study reporting conventional MR imaging findings in fetuses with congenital heart disease. Our results suggest that brain abnormalities are prevalent but relatively mild antenatally in fetuses with congenital heart disease. The long-term predictive value of these findings awaits further study.

Delusional belief flexibility and informal caregiving relationships in psychosis: a potential cognitive route for the protective effect of social support.

Aims. For people with psychosis, contact with informal caregivers is an important source of social support, associated with recovery, and with better outcomes following individual cognitive therapy (CBTp). In this study, we tested whether increased flexibility in delusional thinking, an established predictor of positive outcome following CBTp, was a possible mechanism underlying this effect. Methods. 219 participants with delusions (mean age 38 years; 71% male; 75% White) were grouped according to the presence of a caregiver (37% with a caregiver) and caregiver level of expressed emotion (High/Low EE, 64% Low). Delusional belief flexibility was compared between groups, controlling for interpersonal functioning, severity of psychotic symptoms, and other hypothesised outcome predictors. Results. Participants with caregivers were nearly three times more likely than those without to show flexibility (OR = 2.7, 95% CI 1.5 to 5.0, p = 0.001), and five times more likely if the caregiving relationship was Low EE (OR = 5.0, 95% CI 2.0-13.0, p = 0.001). ORs remained consistent irrespective of controlling for interpersonal functioning and other predictors of outcome. Conclusions. This is the first evidence that having supportive caregiving relationships is associated with a specific cognitive attribute in people with psychosis, suggesting a potential cognitive mechanism by which outcomes following CBTp, and perhaps more generally, are improved by social support.

Long-term survival in horses with strangulating obstruction of the small intestine managed without resection.

REASONS FOR PERFORMING STUDY: Although many studies have described results after small intestinal resection and anastomosis in horses, few have described the outcome in horses with strangulating lesions managed without resection. OBJECTIVES: To examine short- and long-term recoveries in horses with strangulated small intestine that was judged to be viable during surgery and not resected. STUDY DESIGN: Retrospective analysis of case records. METHODS: Data were reviewed from all cases (35 horses) with colic caused by small intestinal strangulation that underwent surgery between 1996 and 2011 at 2 university hospitals and that were managed without resection by 2 surgeons who used a clinical grading system to assess intestinal viability. Kaplan-Meier analyses were used to examine long-term survival. RESULTS: Survival to discharge from the hospital was 100%, and post operative complications developed in 11 horses (31%). Three horses (8.6%) required repeat coeliotomy because of persistent pain with or without reflux, and they responded favourably to decompression of distended intestine. Ten horses died after discharge, and 12 were still alive at follow-up from 20 to 192 months after surgery. Information was available on 13 horses after discharge, but these were eventually lost to follow-up. Kaplan-Meier analyses yielded a median survival probability of 120 months. CONCLUSIONS: A subjective method of assessing small intestinal viability in strangulated small intestine in horses, as used in this study, could reduce the need for resection and anastomosis, with the associated complications and costs. Also, the favourable post operative course in these horses provides strong evidence that early referral could avoid the need for resection and improve survival. The numbers of horses with the most severe changes that were not resected were too small to allow a conclusion that such segments should be left in place, and additional criteria might be needed to guide that decision in such cases.