Evaluation of seasonal influences on adrenocorticotropic hormone response to the thyrotropin-releasing hormone stimulation test and its accuracy for diagnosis of pituitary pars intermedia dysfunction.

Pituitary pars intermedia dysfunction (PPID) is an age-related neurodegenerative disorder, affecting >20 % of older horses. There is a need for improved endocrine tests for early disease detection, and the thyrotropin-releasing hormone (TRH) stimulation test has been recommended for diagnosis of early or mild cases. However, it is currently not recommended for year-round use due to marked seasonal variability. The aims of this cohort study were to evaluate effects of month and season on adrenocorticotropic hormone (ACTH) responses to TRH stimulation and to derive monthly cut-offs for PPID diagnosis. Sixty-three horses were assigned to control (n = 17), subclinical PPID (n = 21) and clinical PPID (n = 25) groups, based on a composite reference standard that combined clinical history and examination findings with endocrine test results. TRH stimulation tests were performed monthly for a 12-month period. Circannual changes were evaluated with one- and two-way repeated-measures analysis of variance and receiver operating characteristic curve analysis was used to derive cut-off values for basal and TRH-stimulated ACTH. TRH-stimulated ACTH concentrations were lowest in February-May and highest in August-October. Specificity of both basal and 30 min post-TRH ACTH was generally higher than sensitivity, and TRH stimulation had improved diagnostic accuracy compared to basal ACTH, although its sensitivity was not significantly greater year-round. TRH stimulation tests yielded considerably more positive results than basal ACTH in the subclinical group, but few additional positive results in clinical PPID cases. There were large differences between cut-offs that maximised sensitivity or specificity for TRH-stimulated ACTH, highlighting the importance of considering clinical presentation alongside test results in diagnostic decision-making.

FORWARDS-1: an adaptive, single-blind, placebo-controlled ascending dose study of acute baclofen on safety parameters in opioid dependence during methadone-maintenance treatment-a pharmacokinetic-pharmacodynamic study.

BACKGROUND: Treatment of opiate addiction with opiate substitution treatment (e.g. methadone) is beneficial. However, some individuals desire or would benefit from abstinence but there are limited options to attenuate problems with opiate withdrawal. Preclinical and preliminary clinical evidence suggests that the GABA-B agonist, baclofen, has the desired properties to facilitate opiate detoxification and prevent relapse. This study aims to understand whether there are any safety issues in administering baclofen to opioid-dependent individuals receiving methadone. METHODS: Opiate-dependent individuals (DSM-5 severe opioid use disorder) maintained on methadone will be recruited from addiction services in northwest London (NHS and third sector providers). Participants will be medically healthy with no severe chronic obstructive pulmonary disease or type 2 respiratory failure, no current dependence on other substances (excluding nicotine), no current severe DSM-5 psychiatric disorders, and no contraindications for baclofen or 4800 IU vitamin D (placebo). Eligible participants will be randomised in a 3:1 ratio to receive baclofen or placebo in an adaptive, single-blind, ascending dose design. A Bayesian dose-escalation model will inform the baclofen dose (10, 30, 60, or 90 mg) based on the incidence of 'dose-limiting toxicity' (DLT) events and participant-specific methadone dose. A range of respiratory, cardiovascular, and sedative measures including the National Early Warning Score (NEWS2) and Glasgow Coma Scale will determine DLT. On the experimental day, participants will consume their usual daily dose of methadone followed by an acute dose of baclofen or placebo (vitamin D3) ~ 1 h later. Measures including oxygen saturation, transcutaneous CO2, respiratory rate, QTc interval, subjective effects (sedation, drug liking, craving), plasma levels (baclofen, methadone), and adverse events will be obtained using validated questionnaires and examinations periodically for 5 h after dosing. DISCUSSION: Study outcomes will determine what dose of baclofen is safe to prescribe to those receiving methadone, to inform a subsequent proof-of-concept trial of the efficacy baclofen to facilitate opiate detoxification. To proceed, the minimum acceptable dose is 30 mg of baclofen in patients receiving ≤ 60 mg/day methadone based on the clinical experience of baclofen's use in alcoholism and guidelines for the management of opiate dependence. TRIAL REGISTRATION: Clinicaltrials.gov NCT05161351. Registered on 16 December 2021.

Anaesthetic management for robotic-assisted laparoscopic prostatectomy: the first UK national survey of current practice.

Robotic-assisted laparoscopic prostatectomy (RALP) is the most common robotic surgical procedure, but there are little published data to inform anaesthetic practice. We aimed to characterise the range of anaesthetic practice for RALP in the United Kingdom through a national survey. We conducted an online national survey to determine current anaesthetic practice for RALP. The survey was distributed to all NHS hospitals within the UK that perform RALP. Thirty-four (79%) of 43 hospitals responded to the survey. Fourteen (41%) centres routinely provide spinal anaesthesia and 79% of these use diamorphine as their intrathecal opioid of choice. Thirty-one (91%) centres administer intravenous strong opioids intraoperatively, and a wide range of non-opioid analgesic agents are also administered. Five (15%) centres reported that they discharge a minority of patients on the day of surgery. High-volume centres are more likely to have a formalised enhanced recovery after surgery (ERAS) pathway and to provide ambulatory surgery for selected patients. This represents the first UK national survey of anaesthetic practice for RALP. The results of the survey revealed significant variation in anaesthetic practice implying a lack of consensus on best perioperative management.

Survey of UK-based veterinary surgeons' opinions on the use of surgery and chemotherapy in the treatment of canine high-grade mast cell tumour, splenic haemangiosarcoma and appendicular osteosarcoma.

The objective of this study was to determine the frequency of recommendation of adjuvant chemotherapy by UK-based general veterinary practitioners (GVPs) for canine patients with high-grade mast cell tumours (HGMCTs), splenic haemangiosarcomas (SHSs) and appendicular osteosarcomas (AOSs); to determine which chemotherapeutic protocols are used by GVPs; and to evaluate reasons why chemotherapy may or may not be recommended postoperatively. An internet survey was created in 2013 using an online programme and was distributed to GVPs. Questions relating to the use of adjuvant chemotherapy for three tumours were selected. In total, 300 responses were generated. Surgery was seen as primary therapy by most GVPs for HGMCT (91 per cent) and SHS (88 per cent), but less frequently for AOS (59 per cent). Also, 90, 40 and 57 per cent of respondents recommended adjuvant chemotherapy for HGMCT, SHS and AOS, respectively. Of these, an appropriate chemotherapy protocol was not known by 25, 51 and 36 per cent of GVPs for HGMCT, SHS and AOS, respectively. From the GVPs not recommending chemotherapy, 29, 64 and 66 per cent did not believe chemotherapy to be efficacious for these tumours. The frequency of recommendation regarding postoperative chemotherapy is variable by tumour type. Reasons given why postoperative chemotherapy is not recommended also vary by tumour type.

Modulation of cellular innate immunity by Lepeophtheirus salmonis secretory products.

Lepeophtheirus salmonis produces pharmacologically active substances that have been shown to modify genetic expression of inflammatory mediators in SHK-1 cells and head kidney macrophages of salmon. Differences in genetic expression among genera of Oncorhynchus and Salmo reflect different susceptibilities to L. salmonis. This study was conducted to determine if the presence of L. salmonis secretory products (SEPs)(1) alters the cellular innate immune response (specifically macrophage function) among several salmonids. Phagocytic assays were performed using SHK-1 cells and macrophages isolated from pink (Oncorhynchus gorbuscha), chum (Oncorhynchus keta) and Atlantic (Salmo salar) salmon following incubation with SEPs and Aeromonas salmonicida. Respiratory burst assays were analyzed using pink, chum and Atlantic salmon macrophages after exposure to SEPs. For SHK-1 cells, incubation with SEPS led to dose-dependent increases in phagocytosis. Following incubation with SEPs, chum salmon macrophages had the highest phagocytic index (55.1%) followed by Atlantic (26.4%) and pink (15.8%) salmon. In contrast, respiratory burst response was greatest in pink salmon and minimal in the other two species. Our results suggest that the cellular innate immune response of salmon is modified in the presence of L. salmonis secretions and differences observed among species provide insight into species-specific consequences of sea lice infection.

Measuring the unmet supportive care needs of cancer support persons: the development of the support person's unmet needs survey--short form.

Few rigorous measures of unmet needs have been developed for cancer support persons. This study describes the development of a short version of the Support Person's Unmet Needs Survey (SPUNS). Cancer survivors [n = 1589, 612 (52%) men, mean age of 62.5 years, SD 11.5] 1-5 years post diagnosis and recruited through three Canadian population-based cancer registries were asked to pass a survey package on to their principal support person. Surveys were returned by 1183 support persons. The survey included the long form of the SPUNS, which contains 78 items. Fifty-two items were deleted using a combination of expert opinion and statistical criteria. Analysis of the remaining items revealed a five-factor structure. The original factors were retained with the exception of a merging of the personal and emotional needs subscales. Cronbach's alpha co-efficients for all subscales were ≥ 0.87, and intraclass correlation of domain scores of the short and long versions of the SPUNS were high. The SPUNS short form was able to discriminate between support persons of survivors who had (n = 147), and those who had not received treatment in the past month (n = 969). At just 26 items, it is likely to have strong clinical and research applicability.

Placental programming of chronic diseases, cancer and lifespan: a review.

Particular paths of fetal growth are now known to predict a range of disorders in adult life. This is thought to reflect fetal programming, the phenomenon whereby nutrition and other influences during development set the body's organs and systems for life. The thesis of this review is that normal variations in the processes of placental development lead to variations in the supply of nutrients to the fetus and programme a small number of key systems that are linked to later disease. A baby's growth and nutrition depend both on the function of the placenta, reflected in its gross morphology at birth, and on the mother's lifetime nutrition, reflected in her height and weight. In many studies, the effects of placental size and shape on later disease have been examined within different categories of mother's body size. The review shows that variations in gross placental morphology at birth predict a wide range of disorders in later life. Any particular placental phenotype seems to predict a limited number of diseases. Further research into the links between the processes of placentation and the morphology of the placenta at birth is now required. We need to know more about the relative importance of nutrient flow, nutrient balance and the timing of nutritional events in determining disorders in later life. We also need to understand why, compared to other placental mammals, the human placenta is so variable in its morphology and functional capacity.

Radiotherapy and the oral environment the effects of radiotherapy on the hard and soft tissues of the mouth and its management.

Radiation therapy plays an important role in the care of patients with head and neck cancer. When the oral cavity and the salivary glands are exposed to high doses of radiation, there can be dramatic effects on the patient's oral health. The clinical consequences of radiation can include mucositis, hyposalivation, taste loss, osteoradionecrosis, radiation caries and trismus. This paper looks at the available literature regarding the effects of radiotherapy on the oral environment and outlines practical clinical approaches to prevent or reduce the adverse side effects of treatment.

Novel setting for addressing tobacco-related disparities: a survey of community welfare organization smoking policies, practices and attitudes.

Research in the United States and Australia acknowledges the potential of non-government social and community service organizations (SCSOs) for reaching socially disadvantaged smokers. This study aimed to describe SCSO smoking policies and practices, and attitudes of senior staff towards smoking and cessation. It also investigated factors associated with positive tobacco control attitudes. In 2009, a cross-sectional telephone survey was undertaken of senior staff in Australian SCSOs, 149 respondents representing 93 organizations completed the survey (response rate=65%; 93/142). Most service clients (60%) remained in programs for 6 months plus, and 77% attended at least weekly. Although 93% of respondents indicated they had an organizational smoking policy, it often did not include the provision of smoking cessation support. Most respondents indicated that client smoking status was not recorded on case notes (78%). Attitudes were mostly positive towards tobacco control in SCSOs, with a mean (standard deviation) score of 8.3 (2.9) of a possible 13. The practice of assessing clients' interest in quitting was the only statistically significant factor associated with high tobacco control attitude scores. The results suggest that SCSOs are appropriate settings for reaching socially disadvantaged smokers with cessation support. Although generally receptive to tobacco control, organizations require further support to integrate smoking cessation support into usual care. In particular, education, training and support for staff to enable them to help their clients quit smoking is important.

Sir Richard Doll Lecture. Developmental origins of chronic disease.

Coronary heart disease, type 2 diabetes, breast cancer and many other chronic diseases are unnecessary. Their occurrence is not mandated by genes passed down to us through thousands of years of evolution. Chronic diseases are not the inevitable lot of humankind. They are the result of the changing pattern of human development. We could readily prevent them, had we the will to do so. Prevention of chronic disease, and an increase in healthy ageing require improvement in the nutrition of girls and young women. Many babies in the womb in the Western world today are receiving unbalanced and inadequate diets. Many babies in the developing world are malnourished because their mothers are chronically malnourished. Protecting the nutrition and health of girls and young women should be the cornerstone of public health. Not only will this prevent chronic disease, but it will produce new generations who have better health and well-being through their lives.

Enhanced beta cell proliferation in mice overexpressing a constitutively active form of Akt and one allele of p21Cip.

AIMS/HYPOTHESIS: The ability of pancreatic beta cells to proliferate is critical both for normal tissue maintenance and in conditions where there is an increased demand for insulin. Protein kinase B(Akt) plays a major role in promoting proliferation in many cell types, including the insulin-producing beta cells. We have previously reported that mice overexpressing a constitutively active form of Akt(caAkt (Tg)) show enhanced beta cell proliferation that is associated with increased protein levels of cyclin D1, cyclin D2 and cyclin-dependent kinase inhibitor 1A (p21(Cip)). In the present study, we sought to assess the mechanisms responsible for augmented p21(Cip) levels in caAkt(Tg) mice and test the role of p21(Cip) in the proliferative responses induced by activation of Akt signalling. METHODS: To gain a greater understanding of the relationship between Akt and p21(Cip), we evaluated the mechanisms involved in the modulation of p2(Cip) by Akt and the in vivo role of reduced p21(Cip) in proliferative responses induced by Akt. RESULTS: Our experiments showed that Akt signalling regulates p21(Cip) transcription and protein stability. caAkt(Tg) /p21(Cip+/-) mice exhibited fasting and fed hypoglycaemia as well as hyperinsulinaemia when compared with caAkt(Tg) mice. Glucose tolerance tests revealed improved glucose tolerance in caAkt(Tg)/p21(Cip+/-) mice compared with caAkt (Tg). These changes resulted from increased proliferation, survival and beta cell mass in caAkt(Tg)/p21(Cip+/-) compared with caAkt(Tg) mice. CONCLUSIONS/INTERPRETATION: Our data indicate that increased p21(Cip) levels in caAkt(Tg) mice act as a compensatory brake, protecting beta cells from unrestrained proliferation. These studies imply that p21(Cip) could play important roles in the adaptive responses of beta cells to proliferate in conditions such as in insulin resistance.

Supporting cystic fibrosis disease management during adolescence: the role of family and friends.

BACKGROUND: Successful management of a complex disease, such as cystic fibrosis (CF), requires support from family and friends; however, few studies have examined social support in adolescents with CF. METHODS: Twenty-four adolescents were interviewed about the support they receive from family and friends. Interviews were transcribed, coded and analysed to determine the types, frequency and perceived supportiveness of specific behaviours. RESULTS: Both family and friends provided treatment-related support to adolescents with CF. Family provided more tangible support and friends provided more relational support. Adolescents also reported that the manner, timing and context of support behaviours influenced their perceptions of the behaviours' supportiveness. A subset of adolescents (17%) chose not to disclose their diagnosis to their friends. CONCLUSIONS: The provision of support appears to be distinct from adolescent's perception of support and there may be some behaviours, such as treatment reminders, that are important to disease management but viewed as less supportive by adolescents. Facilitating increased social support holds the promise of improving disease management during adolescents, but more work is need to understand which aspects of support are related to management outcomes.

Demonstration of ignition radiation temperatures in indirect-drive inertial confinement fusion hohlraums.

We demonstrate the hohlraum radiation temperature and symmetry required for ignition-scale inertial confinement fusion capsule implosions. Cryogenic gas-filled hohlraums with 2.2 mm-diameter capsules are heated with unprecedented laser energies of 1.2 MJ delivered by 192 ultraviolet laser beams on the National Ignition Facility. Laser backscatter measurements show that these hohlraums absorb 87% to 91% of the incident laser power resulting in peak radiation temperatures of T(RAD)=300 eV and a symmetric implosion to a 100 µm diameter hot core.

Cutting the research pie: a value-weighting approach to explore perceptions about psychosocial research priorities for adults with haematological cancers.

Despite the burden of illness associated with haematological cancers, little research is available about improving psychosocial outcomes for this group. Given scarce research funds, it is important to ensure that resources are used strategically for improving their psychosocial well-being. This study aimed to identify the perceptions of professionals, patients and carers regarding prioritising psychosocial research efforts. First, an expert panel's views on priorities for research were identified. This was followed by a web survey to obtain the perceptions of 117 health professionals, patients and carers. The value-weighting survey used points allocation, allowing respondents to indicate the relative priority of each option. A substantial proportion of resources were allocated to patients who were newly diagnosed or receiving treatment. Less priority was given to other stages of the cancer journey or non-patient populations. There was no indication that any type of psychosocial research was a priority; however, some differences were identified when comparing the priorities of the three respondent groups. To improve psychosocial outcomes for haematological cancer patients, resources should be directed towards patients in the early stages of the cancer journey. There may be a need for research investigating potential interventions to improve psychosocial outcomes for patients with haematological cancers.

Vector potential of the salmon louse Lepeophtheirus salmonis in the transmission of infectious haematopoietic necrosis virus (IHNV).

To better understand the role of vector transmission of aquatic viruses, we established an in vivo virus-parasite challenge specifically to address (1) whether Lepeophtheirus salmonis can acquire infectious haematopoietic necrosis virus (IHNV) after water bath exposure or via parasitizing infected Atlantic salmon Salmo salar and if so, define the duration of this association and (2) whether L. salmonis can transmit IHNV to naive Atlantic salmon and whether this transmission requires attachment to the host. Salmon lice which were water bath-exposed to 1 x 10(5) plaque-forming units (pfu) ml(-1) of IHNV for 1 h acquired the virus (2.1 x 10(4) pfu g(-1)) and remained IHNV-positive for 24 h post exposure. After parasitizing IHNV-infected hosts (viral titer in fish mucus 3.3 x 10(4) pfu ml(-1)) salmon lice acquired IHNV (3.4 x 10(3) pfu g(-1)) and remained virus-positive for 12 h. IHNV-positive salmon lice generated through water bath exposure or after parasitizing infected Atlantic salmon successfully transmitted IHNV, resulting in 76.5 and 86.6% of the exposed Atlantic salmon testing positive for IHNV, respectively. In a second experiment, only salmon lice that became IHNV-positive through water bath exposure transmitted IHNV to 20% of the naive fish, and no virus was transmitted when IHNV-infected salmon lice were cohabitated but restrained from attaching to naive fish. Under laboratory conditions, adult L. salmonis can acquire IHNV and transmit it to naive Atlantic salmon through parasitism. However, the ephemeral association of IHNV with L. salmonis indicates that the salmon louse act as a mechanical rather than a biological vector or reservoir.

Interaction between prenatal growth and high-risk genotypes in the development of type 2 diabetes.

AIMS/HYPOTHESIS: Early environmental factors and genetic variants have been reported to be involved in the pathogenesis of type 2 diabetes. The aim of this study was to investigate whether there is an interaction between birthweight and common variants in the TCF7L2, HHEX, PPARG, KCNJ11, SLC30A8, IGF2BP2, CDKAL1, CDKN2A/2B and JAZF1 genes in the risk of developing type 2 diabetes. METHODS: A total of 2,003 participants from the Helsinki Birth Cohort Study, 311 of whom were diagnosed with type 2 diabetes by an OGTT, were genotyped for the specified variants. Indices for insulin sensitivity and secretion were calculated. RESULTS: Low birthweight was associated with type 2 diabetes (p = 0.008) and impaired insulin secretion (p = 0.04). Of the tested variants, the risk variant in HHEX showed a trend towards a low birthweight (p = 0.09) and the risk variant in the CDKN2A/2B locus was associated with high birthweight (p = 0.01). The TCF7L2 risk allele was associated with increased risk of type 2 diabetes. Pooling across all nine genes, each risk allele increased the risk of type 2 diabetes by 14%. [corrected] Risk variants in the HHEX, CDKN2A/2B and JAZF1 genes interacted with birthweight, so that the risk of type 2 diabetes was highest in those with lower birthweight (p

Outcomes of elderly patients aged 80 and over with symptomatic, severe aortic stenosis: impact of patient's choice of refusing aortic valve replacement on survival.

BACKGROUND: Aortic valve replacement (AVR) can be performed safely in selected elderly patients with aortic stenosis (AS). However, the survival benefits of AVR over conservative treatment have not been convincingly demonstrated in AS patients aged above 80. AIM: To investigate the outcomes of patients aged 80 and over with symptomatic, severe AS and by analyzing the effects of patient's choice in either agreeing or refusing to undergo AVR, determine the survival benefits afforded by AVR. DESIGN: Cohort study. METHODS: Subjects aged 80 and over with severe symptomatic AS, diagnosed between 2001 and 2006 were segregated into three groups: subjects who underwent AVR (Group A); patients who were fit for AVR but declined surgery due to personal choice (Group B) and those who were not fit for surgery and were managed conservatively (Group C). Follow-up was conducted by out-patient attendances, review of medical records and telephone interviews. The primary endpoint was all-cause mortality. RESULTS: A total of 103 patients (86.0 +/- 4.2 years, 41% male) were identified and no patient was lost during follow-up. In Group A (n = 17), all 15 patients who underwent AVR were alive after 3.6 +/- 1.4 years follow-up and 2 died whilst awaiting AVR. Seventy-four percent of Group B (n = 24) and 76% of Group C (n = 62) died during follow-up. Group A had significantly better survival than B and C. (P < 0.01) Amongst patients fit for AVR with similar operative risks (Groups A and B), refusal to undergo surgery (hazard ratio 12.61, P = 0.001) was the only predictor of mortality in a multivariate model. CONCLUSION: For elderly AS patients fit for surgery, the patient's decision to refuse AVR is associated with a >12-fold increase in mortality risk. These findings have significant implications for informed decision-making when managing the fit, elderly patient with AS.

Constraints on food choices of women in the UK with lower educational attainment.

OBJECTIVE: Women of lower educational attainment have less balanced and varied diets than women of higher educational attainment. The diets of women are vital to the long-term health of their offspring. The present study aimed to identify factors that influence the food choices of women with lower educational attainment and how women could be helped to improve those choices. DESIGN: We conducted eight focus group discussions with women of lower educational attainment to identify these factors. We contrasted the results of these discussions with those from three focus group discussions with women of higher educational attainment. SETTING: Southampton, UK. SUBJECTS: Forty-two white Caucasian women of lower educational attainment and fourteen of higher educational attainment aged 18 to 44 years. RESULTS: The dominant theme in discussions with women of lower educational attainment was their sense that they lacked control over food choices for themselves and their families. Partners and children exerted a high degree of control over which foods were bought and prepared. Women's perceptions of the cost of healthy food, the need to avoid waste, being trapped at home surrounded by opportunities to snack, and having limited skill and experience with food, all contributed to their sense they lacked control over their own and their family's food choices. CONCLUSIONS: An intervention to improve the food choices of women with lower educational attainment needs to increase their sense of control over their diet and the foods they buy. This might include increasing their skills in food preparation.

Birth size, adult body composition and muscle strength in later life.

OBJECTIVE: Low birth weight has been linked to lower lean body mass and abdominal obesity later in life, whereas high birth weight has been suggested to predict later obesity as indicated by high body mass index (BMI). We examined how birth weight was related to adult body size, body composition and grip strength. DESIGN/SUBJECTS: Cross-sectional study on 928 men and 1075 women born in 1934-1944, with measurements at birth recorded. MEASUREMENTS: Height, weight, waist and hip circumference and isometric grip strength were measured. Lean and fat body mass were estimated by bioelectrical impedance with an eight-polar tactile electrode system. RESULTS: A 1 kg increase in birth weight corresponded in men to a 4.1 kg (95% CI: 3.1, 5.1) and in women to a 2.9 kg (2.1, 3.6) increase in adult lean mass. This association remained significant after adjustment for age, adult body size, physical activity, smoking status, social class and maternal size. Grip strength was positively related to birth weight through its association with lean mass. The positive association of birth weight with adult BMI was explained by its association with lean mass. Low birth weight was related to higher body fat percentage only after adjustment for adult BMI. Abdominal obesity was not predicted by low birth weight. CONCLUSIONS: Low birth weight is associated with lower lean mass in adult life and thus contributes to the risk of relative sarcopenia and the related functional inability at the other end of the lifespan. At a given level of adult BMI, low birth weight predicts higher body fat percentage.

A possible link between prenatal exposure to famine and breast cancer: a preliminary study.

In a study of 475 women born around the 1944-1945 Dutch famine, women exposed to prenatal famine more often reported a history of breast cancer than nonexposed women (hazard ratio, 2.6; 95% confidence interval, 0.9-7.7). They also had alterations in reproductive risk factors. Prenatal famine may increase breast cancer incidence.