Testing a model of fear of cancer recurrence or progression: the central role of intrusions, death anxiety and threat appraisal.

We recently proposed a model of cancer-related anxiety to account for the etiology and maintenance of clinically significant anxiety in the context of cancer. This study tested predictions arising from the model to explain fear of cancer recurrence or progression (FCR). Patients with cancer were recruited from a research registry or outpatient hospital clinics (n = 211). In bivariate analyses, FCR was associated with metacognitive beliefs, intolerance of uncertainty, core belief disruption, less meaning in life, social constraints, death anxiety, intrusions, threat appraisal, and coping. A hierarchical regression explained 65% of the variance in FCR. FCR was predicted by younger age, intrusions, death anxiety, threat appraisal and meta-cognitions. The findings highlight the importance of both cognitive processes and content in FCR, including intrusions, fears about death and dying, beliefs about worry, and threat appraisals.

Fear of cancer recurrence and death anxiety.

In 2013, 3 systematic reviews of fear of cancer recurrence (FCR) and its predictors were published. All 3 concurred that FCR is a highly prevalent problem and amongst the largest unmet needs of cancer survivors, even 5 or more years after treatment. However, between them they identified only 1 study that had investigated the relationship between death anxiety and FCR. This is surprising because it is well acknowledged that a diagnosis of cancer, a potentially life-threatening illness, is associated with a number of existential issues that give rise to psychological sequelae such as intrusive thoughts about death and other post-traumatic symptoms. Outside the cancer literature, there has recently been a call to identify death anxiety as a transdiagnostic construct that underlies many anxiety disorders even in healthy people. And yet, the relevance of death anxiety to FCR has not been studied. We explore the barriers to the study of death anxiety and FCR and the reasons that a potential link between the 2 might have important theoretical and clinical implications. We conclude that establishing the relationship between death anxiety, FCR and other existential issues is essential in order to fully understand FCR, particularly in the context of advanced disease. We further conclude that whether death anxiety underlies FCR has important clinical implications which would potentially allow us to optimise currently available evidence-based treatments.

Attentional bias and metacognitions in cancer survivors with high fear of cancer recurrence.

BACKGROUND: Fear of cancer recurrence (FCR) is a common and severe problem amongst cancer survivors, but mechanisms to explain its development and maintenance are still lacking. The self-regulatory executive function (S-REF) model suggests that metacognitions and attentional bias to cancer-related words may explain high FCR. Thus, this study aimed to explore relationships between FCR, metacognitions and attentional bias in a mixed group of cancer survivors. METHOD: Sixty-three early-stage breast or prostate cancer survivors, diagnosed within 6 months to 5 years prior to participation and who had completed all hospital-based treatment with no evidence of cancer recurrence were recruited through two metropolitan oncology clinics. Participants completed a questionnaire battery and the dot-probe task. RESULTS: Survivors with clinical FCR had significantly greater positive beliefs about worry (10.1 vs 7.4, p = 0.002) and beliefs about the uncontrollability and danger of worry (12.0 vs 7.7, p = 0.000) than those with non-clinical FCR, whereas the total metacognition score significantly predicted FCR in multiple regression analysis (ß = 0.371, p = 0.001). No significant differences were detected between participants scoring above and below clinical FCR levels in attention bias indices. CONCLUSIONS: This study found partial support for the S-REF model of FCR, with metacognitions but not attentional bias found to be related to FCR. Further research is needed to explore attentional biases in more detail.

The motherhood choices decision aid for women with rheumatoid arthritis increases knowledge and reduces decisional conflict: a randomized controlled trial.

BACKGROUND: For many women with Rheumatoid Arthritis (RA) motherhood decisions are complicated by their condition and complex pharmacological treatments. Decisions about having children or expanding their family require relevant knowledge and consultation with their family and physician as conception and pregnancy has to be managed within the RA context. Relevant information is not readily available to women with RA. Therefore a randomized controlled study was conducted to evaluate the effectiveness of a new motherhood decision aid (DA) developed specifically for women with RA. METHODS: One hundred and forty-four women were randomly allocated to either an intervention or control group. All women completed a battery of questionnaires at pre-intervention, including, the Pregnancy in Rheumatoid Arthritis Questionnaire (PiRAQ), the Decisional Conflict Scale (DCS), the Hospital Anxiety and Depression Scale (HADS), and the Arthritis Self-Efficacy Scale (ASES), and provided basic demographic information. Women in the DA group were sent an electronic version of the DA, and completed the battery of questionnaires for a second time post-intervention. RESULTS: Women who received the DA had a 13 % increase in relevant knowledge (PiRAQ) scores and a 15 % decrease in scores on the decisional conflict (DCS), compared to the control group (1 %, 2 % respectively). No adverse psychological effects were detected as evident in unchanged levels of depression and anxiety symptoms. CONCLUSIONS: The findings of this study suggest that this DA may be an effective tool in assisting women with RA when contemplating having children or more children. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, http://www.anzctr.org.au/ , ACTRN12615000523505.

The psychosocial impact associated with diabetes-related amputation.

AIMS: Research has suggested that the additional impact of a diabetes-related amputation is associated with poorer physical functioning, poorer psychosocial outcome and greater body image disturbance. However, no study to date has compared patients with diabetes with and without amputation and adequately controlled for additional medical morbidity often found among individuals with an amputation. The aim of this study was to statistically control for any group differences on medical and demographic variables to examine the isolated psychosocial impact of diabetes-related amputation. METHODS: Individuals with diabetes with an amputation (n = 50) were compared to a control sample (individuals with diabetes without an amputation; n = 240). All participants completed a demographic and medical questionnaire, as well as measures of psychological distress, quality of life and body image. RESULTS: The results indicated that, in univariate analyses, depression, physical quality of life and body image disturbance were all poorer in the amputee group. These differences remained for body image disturbance (P = 0.005), but were no longer significant for depression or physical quality of life in multivariate analyses controlling for important demographic and medical variables. CONCLUSIONS: The present study found that the impact of diabetes-related amputation was significant for body image disturbance. However, it appears that other psychosocial outcomes are better accounted for by medical co-morbidities common in this group rather than the amputation itself. This research certainly highlights that clinicians must assess for and address all potential medical contributors to psychosocial outcomes, rather than assuming that people will experience poorer outcomes following amputation.

Current approaches to managing fear of cancer recurrence; a descriptive survey of psychosocial and clinical health professionals.

OBJECTIVE: Fear of cancer recurrence (FCR) is common amongst cancer survivors and help with this problem is the most frequently reported unmet need in this population. This study investigated how FCR is perceived and managed by clinical health professionals (medical and nursing staff) and psychosocial professionals in oncology settings. METHODS: Clinical health professionals and psychosocial professionals in oncology settings received emailed invitations from their professional organisation to participate in an online survey. RESULTS: Data from 77 clinical health professionals and 64 psychosocial professionals indicate that FCR is perceived as common and challenging to manage. Thirty-one percent of psychosocial professionals estimated FCR is present in >50% of cancer survivors seen in their practise. Only a minority (21%) of clinical staff reported always referring patients with high levels of FCR to psychosocial support. Strategies for managing FCR differed considerably amongst psychosocial professionals, and most reported that aspects of acceptance and commitment therapy and/or cognitive behaviour therapy were helpful. Greater than 99% of participants were interested in training to help patients manage FCR. CONCLUSIONS: Fear of cancer recurrence is commonly identified in oncology settings and a common focus of discussion in follow-up care. However, patients with high levels of FCR are not routinely referred to psychosocial staff, and barriers to referral to psychosocial care should be investigated. The diversity of approaches reported by psychosocial professionals suggests lack of consensus regarding management of FCR, indicating that the development effective, theoretical-based intervention and evidence-based intervention for FCR is a matter of priority.

Total colourblindness is caused by mutations in the gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated cation channel.

Total colourblindness (OMIM 216900), also referred to as rod monochromacy (RM) or complete achromatopsia, is a rare, autosomal recessive inherited and congenital disorder characterized by photophobia, reduced visual acuity, nystagmus and the complete inability to discriminate between colours. Electroretinographic recordings show that in RM, rod photoreceptor function is normal, whereas cone photoreceptor responses are absent. The locus for RM has been mapped to chromosome 2q11 (ref. 2), however the gene underlying RM has not yet been identified. Recently, a suitable candidate gene, CNGA3, encoding the alpha-subunit of the cone photoreceptor cGMP-gated cation channel, a key component of the phototransduction pathway, has been cloned and assigned to human chromosome 2q11 (refs 3,4). We report the identification of missense mutations in CNGA3 in five families with RM. Homozygous mutations are present in two families, whereas the remaining families show compound heterozygous mutations. In all cases, the segregation pattern of the mutations is consistent with the autosomal recessive inheritance of the disease and all mutations affect amino acids that are highly conserved among cyclic nucleotide gated channels (CNG) in various species. This is the first report of a colour vision disorder caused by defects other than mutations in the cone pigment genes, and implies at least in this instance a common genetic basis for phototransduction in the three different cone photoreceptors of the human retina.

A possible vulnerability locus for bipolar affective disorder on chromosome 21q22.3.

In a preliminary genome scan of 47 bipolar disorder families, we detected in one family a lod score of 3.41 at the PFKL locus on chromosome 21q22.3. The lod score is robust to marker allele frequencies, phenocopy rates and age-dependent penetrance, and remains strongly positive with changes in affection status. Fourteen other markers in 21q22.3 were tested on this family, with largely positive lod scores. Five of the other 46 families also show positive, but modest lod scores with PFKL. When all 47 families are analysed together, there is little support for linkage to PFKL under homogeneity or heterogeneity using lod score analysis, but the model-free affected-pedigree-member method yields statistically significant results (p < 0.0003). Our results are consistent with the presence of a gene in 21q22.3 predisposing at least one family to bipolar disorder.

Intrasexual competition and sexual selection in cooperative mammals.

In most animals, the sex that invests least in its offspring competes more intensely for access to the opposite sex and shows greater development of secondary sexual characters than the sex that invests most. However, in some mammals where females are the primary care-givers, females compete more frequently or intensely with each other than males. A possible explanation is that, in these species, the resources necessary for successful female reproduction are heavily concentrated and intrasexual competition for breeding opportunities is more intense among females than among males. Intrasexual competition between females is likely to be particularly intense in cooperative breeders where a single female monopolizes reproduction in each group. Here, we use data from a twelve-year study of wild meerkats (Suricata suricatta), where females show high levels of reproductive skew, to show that females gain greater benefits from acquiring dominant status than males and traits that increase competitive ability exert a stronger influence on their breeding success. Females that acquire dominant status also develop a suite of morphological, physiological and behavioural characteristics that help them to control other group members. Our results show that sex differences in parental investment are not the only mechanism capable of generating sex differences in reproductive competition and emphasize the extent to which competition for breeding opportunities between females can affect the evolution of sex differences and the operation of sexual selection.

The impact of COVID-19 on cancer patients, their carers and oncology health professionals: A qualitative study.

OBJECTIVE: Cancer patients, carers and oncology health professionals have been impacted by the COVID-19 pandemic in many ways, but their experiences and psychosocial responses to the pandemic are still being explored. This study aimed to document the experience of Australians living with cancer, family carers, and Oncology health professionals (HPs) when COVID-19 first emerged. METHODS: In this qualitative study, participants (cancer patients currently receiving treatment, family carers and HPs) completed a semi-structured interview exploring their experiences of COVID-19 and the impact it had on cancer care. Participants also completed the Hospital Anxiety and Depression Scale (patients) and the Depression, Anxiety and Stress Scale (carers and HPs) to assess emotional morbidity. Thematic analysis was undertaken on qualitative data. RESULTS: 32 patients, 16 carers and 29 HPs participated. Qualitative analysis yielded three shared themes: fear and death anxiety, isolation, and uncertainty. For HPs, uncertainty incorporated the potential for moral distress and work-stress. Patients and carers scoring high on anxiety/depression measures were more likely to have advanced disease, expressed greater death anxiety, talked about taking more extreme precautionary measures, and felt more impacted by isolation. CONCLUSION: Cancer and COVID-19 can have compounding psychological impacts on all those receiving or giving care. PRACTICE IMPLICATIONS: Screening for distress in patients, and burnout in HPs, is recommended. Increased compassionate access and provision of creative alternatives to face-to-face support are warrented.

Pre-Exposure, But Not Overshadowing, Inhibits Nocebo Hyperalgesia.

Nocebo hyperalgesia is a pervasive problem that significantly adds to the burden of pain. Conditioning is a key mechanism of nocebo hyperalgesia and recent evidence indicates that, once established, nocebo hyperalgesia is resistant to extinction. This means that preventive strategies are critical. We therefore tested whether two novel strategies - overshadowing (Experiment 1) and pre-exposure (Experiment 2) - could inhibit conditioned nocebo hyperalgesia. Overshadowing involves introducing additional cues during conditioning that should compete with and overshadow learning about the target nocebo cue. Pre-exposure involves pre-exposing the target nocebo cue in the absence of pain, which should diminish its ability to become associated with pain later. In both studies, healthy volunteers (N = 141) received exposure to a series of electrocutaneous pain stimuli with and without a sham electrode 'activated', which they were led to believe was a genuine hyperalgesic treatment. Nocebo conditioning was achieved by pairing sham activation with high pain prior to testing at equivalent pain intensity. In both studies, standard nocebo conditioning led to clear nocebo hyperalgesia relative to natural history controls. In Experiment 1, there was no evidence that overshadowing attenuated nocebo hyperalgesia. Importantly, however, Experiment 2 found that pre-exposure successfully attenuated nocebo hyperalgesia with post hoc analysis suggesting that this effect was dose-dependent. These findings provide novel evidence that pre-exposure, but not overshadowing, could be a cheap and effective way for mitigating the substantial harm caused by conditioned nocebo hyperalgesia in clinical settings. PERSPECTIVE: Nocebo hyperalgesia causes substantial patient burden with few preventive options available. Our study found novel evidence that pre-exposing treatment cues without pain, but not overshadowing them with other cues, has the capacity to inhibit conditioned nocebo hyperalgesia. Pre-exposure may therefore be an effective preventive strategy to combat nocebo hyperalgesia.

Prevention of panic attacks and panic disorder in COPD.

This study examined whether cognitive behavioural therapy (CBT) could prevent the development or worsening of panic-spectrum psychopathology and anxiety symptoms in chronic obstructive pulmonary disease (COPD). 41 patients with COPD, who had undergone pulmonary rehabilitation, were randomised to either a four-session CBT intervention condition (n = 21) or a routine care condition (n = 20). Assessments were at baseline, post-intervention, and at 6-, 12- and 18-month follow-ups. Primary outcomes were the rates of panic attacks, panic disorder and anxiety symptoms. Secondary outcomes were depressive symptoms, catastrophic cognitions about breathing difficulties, disease-specific quality of life and hospital admission rates. There were no significant differences between the groups on outcome measures at baseline. By the 18-month follow-up assessment, 12 (60%) routine care group participants had experienced at least one panic attack in the previous 6 months, with two (17%) of these being diagnosed with panic disorder, while no CBT group participants experienced any panic attacks during the follow-up phase. There were also significant reductions in anxiety symptoms and catastrophic cognitions in the CBT group at all three follow-ups and a lower number of hospital admissions between the 6- and 12-month follow-ups. The study provides evidence that a brief, specifically targeted CBT intervention can treat panic attacks in COPD patients and prevent the development and worsening of panic-spectrum psychopathology and anxiety symptoms.

Antipsychotic drugs upregulate lipogenic gene expression by disrupting intracellular trafficking of lipoprotein-derived cholesterol.

Antipsychotic drugs (APDs) have been reported to induce lipogenic genes. This has been proposed to contribute to their efficacy in treating schizophrenia and other psychiatric disorders, as well as the metabolic side effects often associated with these drugs. The precise mechanism for the lipogenic effects of APDs is unknown, but is believed to involve increased activation of the lipogenic transcription factors, such as sterol regulatory element binding proteins (SREBPs). In a series of experiments in a model cell line, we found that a panel of typical and atypical APDs inhibited transport of lipoprotein-derived cholesterol to the endoplasmic reticulum (ER), which houses the cholesterol homeostatic machinery. APDs belong to the class of cationic amphiphiles and as has been shown for other amphiphiles, caused lipoprotein-derived cholesterol to accumulate intracellularly, preventing it from being esterified in the ER and suppressing SREBP activation. APDs did not activate the liver X receptor, another transcription factor involved in lipogenesis. However, these drugs markedly reduced cholesterol synthesis. This paradoxical result indicates that the upregulation of SREBP-target genes by APDs may not translate to increased cellular cholesterol levels. In conclusion, we have determined that APDs disrupt intracellular trafficking and synthesis of cholesterol, which may have important clinical ramifications.

Temperature in the monkey: transmitter factors released from the brain during thermoregulation.

When perfusate is collected from the anterior hypothalamus of a cooled donor monkey and is transfused to a corresponding hypothalamic site in a normal monkey, fever occurs in this recipient. Conversely, perfusate from a heated donor monkey lowers the recipient monkey's temperature when the same hypothalamic transfusion procedure is followed. These experiments provide direct evidence of a neurochemical "coding" within the specific anatomical region of the brain historically implicated in the control of body temperature.

Brain lesions in an infant rhesus monkey treated with monsodium glutamate.

In an infant rhesus monkey brain damage resulted from subcutaneously administered monosodium glutamate. Although a relatively high dose of monosodium glutamate was used, the infant was asymptomatic for a 3-hour observation period during which time hypothalamic neurons were undergoing a process of acute cell death. With the electron microscope it was observed that dendrites and cell bodies of neurons are the tissue components primarily affected in brain damage induced by monosodium glutamate.

The incremental threshold of the rod visual system and Weber's law.

The incremental threshold of the isolated rod visual system is believed, under certain conditions, to obey Weber's law (that is, to increase in direct proportion to the intensity of the background). This relation was tested at several background wavelengths, over an intensity range for which the target was seen only by the rods. Although the slope on long-wavelength background approximates unity (that is, Weber's law on log-log coordinates), it averages less than 0.8 on short- and middle-wavelength backgrounds. This is the same value as that found for the thresholds of a typical, complete achromat--who lacks cone vision--regardless of background wavelength. These results force the conclusion that Weber's law for incremental threshold detection is achieved not by the rods alone but only by the rods acting together with the cones.

Effects of helpers on juvenile development and survival in meerkats.

Although breeding success is known to increase with group size in several cooperative mammals, the mechanisms underlying these relationships are uncertain. We show that in wild groups of cooperative meerkats, Suricata suricatta, reductions in the ratio of helpers to pups depress the daily weight gain and growth of pups and the daily weight gain of helpers. Increases in the daily weight gain of pups are associated with heavier weights at independence and at 1 year of age, as well as with improved foraging success as juveniles and higher survival rates through the first year of life. These results suggest that the effects of helpers on the fitness of pups extend beyond weaning and that helpers may gain direct as well as indirect benefits by feeding pups.

Cooperation, control, and concession in meerkat groups.

"Limited control" models of reproductive skew in cooperative societies suggest that the frequency of breeding by subordinates is determined by the outcome of power struggles with dominants. In contrast, "optimal skew" models suggest that dominants have full control of subordinate reproduction and allow subordinates to breed only when this serves to retain subordinates' assistance with rearing dominants' own litters. The results of our 7-year field study of cooperative meerkats, Suricata suricatta, support the predictions of limited control models and provide no indication that dominant females grant reproductive concessions to subordinates to retain their assistance with future breeding attempts.

Type II Gaucher disease manifesting as haemophagocytic lymphohistiocytosis.

Haemophagocytic lymphohistiocytosis (HLH) is a rare and rapidly progressive disease which, untreated, invariably leads to death. Gaucher disease is a rare lysosomal storage disorder. The acute neuronopathic variant; type II, is also rapidly progressive. We report an infant with Gaucher disease type II manifesting as HLH. Immunoblot revealed a deficiency of Munc 13-4, an intracellular protein responsible for docking of secretory lysosomes. This, and other possible pathogenetic mechanisms to explain the link are discussed.

Color signals in human motion-selective cortex.

The neural basis for the effects of color and contrast on perceived speed was examined using functional magnetic resonance imaging (fMRI). Responses to S cone (blue-yellow) and L + M cone (luminance) patterns were measured in area V1 and in the motion area MT+. The MT+ responses were quantitatively similar to perceptual speed judgments of color patterns but not to color detection measures. We also measured cortical motion responses in individuals lacking L and M cone function (S cone monochromats). The S cone monochromats have clear motion-responsive regions in the conventional MT+ position, and their contrast-response functions there have twice the responsivity of S cone contrast-response functions in normal controls. But, their responsivity is far lower than the normals' responsivity to luminance contrast. Thus, the powerful magnocellular input to MT+ is either weak or silent during photopic vision in S cone monochromats.